# pos

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lemma:
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# ent

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  The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production


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  Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame ORF 3b ORF 6 and Nucleocapsid Proteins Function


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  Decade Long Structural Studies of SARS Coronavirus Molecular Mechanism for Antibody Dependent Enhancement of Coronavirus Entry C


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  Camelid Antibodies Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease Neutralizing


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  Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid 19 Association of Treatment With Hydroxychloroquine or Azithromycin With In Hospital Mortality in Patients


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  Notice on Issuing a New Coronary Virus Pneumonia Diagnosis and Treatment Plan Trial Version 6 Clinical


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id: cord-294700-pb5k21da
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  Tofacitinib Treatment of Refractory Systemic Juvenile Idiopathic Arthritis JAK Inhibitors in Rheumatology Implications


id: cord-294700-pb5k21da
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  COVID 19 OLUMIANT Highlights of Prescribing Information Critical Assessment of Pharmacokinetic Drug Drug Interaction Potential


id: cord-294700-pb5k21da
type: CHEMICAL
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  Randy Q Bassiri Hamid title Multidisciplinary Guidance Regarding the Use of Immunomodulatory Therapies for Acute COVID


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type: ORG
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  Clınicas da Universidade Federal de Pernambuco United Nations Department of Economic and Social Affairs


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id: cord-005646-xhx9pzhj
type: ORG
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  Mayer Sagv Division of Pediatric Critical Care Medicine Schneider Children s Hospital New Hyde Park NY


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  COVID 19 Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease Clinical


id: cord-299093-zp07aqpm
type: ORG
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  Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2


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type: DISEASE
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  stroke atrial fibrillation chronic renal failure chronic liver disease diabetes mellitus chronic obstructive pulmonary disease COPD


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id: cord-026031-hnf5vayd
type: GGP
entity:
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id: cord-026031-hnf5vayd
type: GGP
entity:
  Angiotensin converting enzyme inhibitors e g enalapril Angiotensin receptor blockers e g losartan Cyclosporine


id: cord-026031-hnf5vayd
type: GGP
entity:
  steroids e g prednisolone methylprednisolone sodium succinate triamcinolone Depending on the severity of the patient s condition consider monitoring using the Rule of Twenty Administer antiemetics and gastroprotectant drugs to treat nausea vomiting and hematemesis Give the patient broad spectrum antibiotics ampicillin


id: cord-026031-hnf5vayd
type: GGP
entity:
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id: cord-026031-hnf5vayd
type: GGP
entity:
  warfarin 0 06 0 09 mg kg day Monitoring therapy based on prothrombin time and the international normalized ratio INR 2 0 4 0


id: cord-026031-hnf5vayd
type: WORK_OF_ART
entity:
  Treatment Treatment of onion chive and garlic toxicity includes administration of intravenous fluid diuresis and induction of


id: cord-026031-hnf5vayd
type: DISEASE
entity:
  pyometra gastrointestinal obstruction intraluminal gastrointestinal foreign body dilated bile duct or gallbladder mucocele


id: cord-026031-hnf5vayd
type: DISEASE
entity:
  hypotension shock coagulopathies lethargy weakness muscle fasciculations lymphangitis rhabdomyolysis


id: cord-026031-hnf5vayd
type: DISEASE
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  concomitant ligamentous or neurologic compromise Box 1 41 Immediately after the initial primary survey of a patient perform a more thorough examination including an orthopedic examination Multiple injuries


id: cord-026031-hnf5vayd
type: CHEMICAL
entity:
  NaCl 2 5 dextrose 150 200 5 0 45 NaCl 2 5 dextrose 100 150 5 0 45 NaCl 2 5 dextrose 100 0 0 45 NaCl 5 dextrose


id: cord-026031-hnf5vayd
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entity:
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id: cord-026031-hnf5vayd
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id: cord-026031-hnf5vayd
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id: cord-026031-hnf5vayd
type: DISEASE
entity:
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id: cord-026031-hnf5vayd
type: CHEMICAL
entity:
  Antihistamines loratadine diphenhydramine doxylamine clemastine meclizine dimenhydrinate chlorpheniramine cyclizine terfenadine hydroxyzine


id: cord-026031-hnf5vayd
type: DISEASE
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  pleural hemorrhage gastrointestinal hemorrhage pericardial hemorrhage hematuria retroperitoneal hemorrhage hemarthrosis


id: cord-332480-3uodkrkp
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  granulocyte colony stimulating factor G CSF granulocytemacrophage colony stimulating factor GM CSF interferon IFN


id: cord-332480-3uodkrkp
type: WORK_OF_ART
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  Takeda Initiates Development of a Plasma Derived Therapy for COVID 19 Grifols Announces Formal Collaboration with US Government to Produce the First Treatment Specifically Targeting COVID 19 Meplazumab treats COVID 19


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  sensitivity C reactive protein Hs CRP C reactive protein CRP 8 mg L interleukin 6 IL 6 glucose D dimer


id: cord-328384-jzfr2t3p
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  BUN Hs Troponin I creatine kinase IL 6 Hs CRP glucose D dimer sodium potassium lactate dehydrogenase


id: cord-328384-jzfr2t3p
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  The Clinical Manifestations and Chest Computed Tomography Findings of Coronavirus Disease 2019 COVID 19 Patients in China


id: cord-328384-jzfr2t3p
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  chronic kidney disease cerebrovascular disease cardiovascular disease diabetes mellitus hypertension


id: cord-335061-wn8u7u9y
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  lymphocyte neutrophil C reactive protein CRP 101 lactic dehydrogenase LDH creatine kinase CK D dimer alanine


id: cord-335061-wn8u7u9y
type: CELL_TYPE
entity:
  lymphocyte neutrophil C reactive 509 protein lactic dehydrogenase creatine kinase D dimer alanine aminotransferase 510 aspartate aminotransferase


id: cord-335061-wn8u7u9y
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  Alanine aminotransferase U L Aspartate aminotransferase U L Total bilirubin umol l Albumin g L Lactate dehydrogenase U L Blood urea nitrogen


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  SARS CoV 2 Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease Clinical Characteristics


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  An Empirical Transition Matrix for Non Homogeneous Markov Chains Based on Censored Observations Multivariate


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  Critical COVID 19 Pneumonia China Medical Treatment Expert Group for Covid 19 Clinical Characteristics of Coronavirus Disease 2019


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id: cord-345371-pjbviagq
type: FAC
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  Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute


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  the Late Endosome Lysosome and Block the Entry of Ebola Virus Middle East Respiratory Syndrome Coronavirus


id: cord-345371-pjbviagq
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  Compassionate Use of Remdesivir for Patients with Severe Covid 19 Remdesivir for the Treatment of Covid 19 Preliminary Report COVID 19


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id: cord-350492-1s6wtj25
type: PROTEIN
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entity:
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id: cord-305583-p2jp5fiq
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# bib

id: cord-000522-d498qj2b
title: Reducing mortality in sepsis: new directions
author: Vincent, Jean-Louis
date: 2002-12-05
txt: ./txt/cord-000522-d498qj2b.txt
cache: ./cache/cord-000522-d498qj2b.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239386/
doi: 10.1186/cc1860
summary:
  Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced. The interventions discussed encompassed low tidal volume in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) (Edward Abraham), early goal-directed therapy (EGDT) (Emanuel Rivers), drotrecogin alfa (activated) (Gordon Bernard), moderate-dose corticosteroids (Djillali Annane), and tight control of blood sugar (Greet Van den Berghe).

abstract:
  Considerable progress has been made in the past few years in the development of therapeutic interventions that can reduce mortality in sepsis. However, encouraging physicians to put the results of new studies into practice is not always simple. A roundtable was thus convened to provide guidance for clinicians on the integration and implementation of new interventions into the intensive care unit (ICU). Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. One of the principal investigators for each study was invited to participate in the roundtable. The discussions and questions that followed the presentation of data by each panel member enabled a consensus recommendation to be derived regarding when each intervention should be used. Each new intervention has a place in the management of patients with sepsis. Furthermore, and importantly, the therapies are not mutually exclusive; many patients will need a combination of several approaches – an 'ICU package'. The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced.


id: cord-001050-lq9tp20z
author: Khanafer, Nagham
date: 2013-08-01
txt: ./txt/cord-001050-lq9tp20z.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750359/
doi: 10.1186/1471-2334-13-359
summary:
  title: Severe leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival BACKGROUND: Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate. The objectives of this study were to define the characteristics of patients with severe leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described. Multivariate analysis indicated that the factors associated with severe leukopenia were influenza-like illness (adjusted odds ratio (aOR) 4.45, 95% CI (95% confidence interval) 1.67-11.88, P=0.003), airway bleeding (aOR 4.53, 95% CI 1.85-11.13, P=0.001) and age over 30 years (aOR 2.69, 95% CI 1.08-6.68, P=0.033). Severe community-acquired pneumonia caused by Panton-Valentine leukocidin-positive Staphylococcus aureus: first reported case in the United Kingdom Factors predicting mortality in necrotizing community-acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine leukocidin

title:
  Severe leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival

abstract:
  BACKGROUND: Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate. Erythroderma, airway bleeding, and leukopenia have been shown to be predictive of mortality. The objectives of this study were to define the characteristics of patients with severe leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described. METHODS: It was designed as a case-case study nested in a cohort study. A total of 148 cases of community-acquired, necrotizing pneumonia were included. The following data were collected: basic demographic information, medical history, signs and symptoms, radiological findings and laboratory results during the first 48 h of hospitalization. The study population was divided into 2 groups: (1) with severe leukopenia (leukocyte count ≤3,000 leukocytes/mL, n=62) and (2) without severe leukopenia (>3,000 leukocytes/mL, n=86). RESULTS: Median age was 22 years, and the male-to-female gender ratio was 1.5. The overall in-hospital mortality rate was 41.2%. Death occurred in 75.8% of severe leukopenia cases with median survival time of 4 days, and in 16.3% of cases with leukocyte count >3,000/mL (P<0.001). Multivariate analysis indicated that the factors associated with severe leukopenia were influenza-like illness (adjusted odds ratio (aOR) 4.45, 95% CI (95% confidence interval) 1.67-11.88, P=0.003), airway bleeding (aOR 4.53, 95% CI 1.85-11.13, P=0.001) and age over 30 years (aOR 2.69, 95% CI 1.08-6.68, P=0.033). A personal history of furuncles appeared to be protective (OR 0.11, 95% CI 0.01-0.96, P=0.046). CONCLUSION: S. aureus-necrotizing pneumonia is still an extremely severe disease in patients with severe leukopenia. Some factors could distinguish these patients, allowing better initial identification to initiate adapted, rapid administration of appropriate therapy.


id: cord-001322-7xmxcm35
author: Walden, Andrew P
date: 2014-04-01
txt: ./txt/cord-001322-7xmxcm35.txt
cache: ./cache/cord-001322-7xmxcm35.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056764/
doi: 10.1186/cc13812
summary:
  Phenotypic data was recorded using a robust clinical database allowing a contemporary analysis of the clinical characteristics, microbiology, outcomes and independent risk factors in patients with severe CAP admitted to ICUs across Europe. A number of more recent, larger studies have focussed on identifying patients with CAP at increased risk of severe sepsis and death, as well as those who may require ventilator or vasopressor support [3, [24] [25] [26] . The aim of the study reported here was to define the clinical characteristics, microbiological aetiology, outcomes and independent risk factors for mortality in a large, contemporary cohort of patients with severe CAP admitted to ICUs across Europe. The British Thoracic Society Research Committee and The Public HealthLaboratory Service: The aetiology, management and outcome of severe community-acquired pneumonia on the intensive care unit A five-year study of severe community-acquired pneumonia with emphasis on prognosis in patients admitted to an intensive care unit

title:
  Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort

abstract:
  INTRODUCTION: Community acquired pneumonia (CAP) is the most common infectious reason for admission to the Intensive Care Unit (ICU). The GenOSept study was designed to determine genetic influences on sepsis outcome. Phenotypic data was recorded using a robust clinical database allowing a contemporary analysis of the clinical characteristics, microbiology, outcomes and independent risk factors in patients with severe CAP admitted to ICUs across Europe. METHODS: Kaplan-Meier analysis was used to determine mortality rates. A Cox Proportional Hazards (PH) model was used to identify variables independently associated with 28-day and six-month mortality. RESULTS: Data from 1166 patients admitted to 102 centres across 17 countries was extracted. Median age was 64 years, 62% were male. Mortality rate at 28 days was 17%, rising to 27% at six months. Streptococcus pneumoniae was the commonest organism isolated (28% of cases) with no organism identified in 36%. Independent risk factors associated with an increased risk of death at six months included APACHE II score (hazard ratio, HR, 1.03; confidence interval, CI, 1.01-1.05), bilateral pulmonary infiltrates (HR1.44; CI 1.11-1.87) and ventilator support (HR 3.04; CI 1.64-5.62). Haematocrit, pH and urine volume on day one were all associated with a worse outcome. CONCLUSIONS: The mortality rate in patients with severe CAP admitted to European ICUs was 27% at six months. Streptococcus pneumoniae was the commonest organism isolated. In many cases the infecting organism was not identified. Ventilator support, the presence of diffuse pulmonary infiltrates, lower haematocrit, urine volume and pH on admission were independent predictors of a worse outcome.


id: cord-002227-x1ddi8wg
author: Li, Wanli
date: 2016-07-29
txt: ./txt/cord-002227-x1ddi8wg.txt
cache: ./cache/cord-002227-x1ddi8wg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038202/
doi: 10.3892/etm.2016.3558
summary:
  In the process of nursing children with severe pneumonia, intensive care was provided, including condition assessment and diagnosis, close observation of disease, keeping the airway unblocked, rational oxygen therapy, prevention and treatment of respiratory and circulatory failure, support of vital organs, complications, and health education. As a result, severe pneumonia produces corresponding clinical symptoms, such as respiratory failure, heart failure, toxic encephalopathy and intestinal paralysis, which endanger the lives of children in the short term, and is the first cause of death of pediatric inpatients (6, 7) . Type I respiratory failure also refers to the coexistence of hypoxemia and hypercapnia, impairment of ventilatory function and gas exchange functions, severe lung lesion, obstruction of trachea and bronchia caused by sticky secretions, blood change of PaO 2 <60 mmHg, and PaCO 2 >50 mmHg. Main clinical manifestations of children patients with type I pneumonia with respiratory failure include, poor mental state or dysphoria, polypnea, cyanosis of lips, dyspnea, nasal flaring and three depression signs.

title:
  Emergency treatment and nursing of children with severe pneumonia complicated by heart failure and respiratory failure: 10 case reports

abstract:
  Pneumonia refers to lung inflammation caused by different pathogens or other factors, and is a common pediatric disease occurring in infants and young children. It is closely related to the anatomical and physiological characteristics of infants and young children and is more frequent during winter and spring, or sudden changes in temperature. Pneumonia is a serious disease that poses a threat to children's health and its morbidity and mortality rank first, accounting for 24.5–65.2% of pediatric inpatients. Due to juvenile age, severe illness and rapid changes, children often suffer acute heart failure, respiratory failure and even toxic encephalopathy at the same time. The concurrence in different stages of the process of emergency treatment tends to relapse, which directly places the lives of these children at risk. Severe pneumonia constitutes one of the main causes of infant mortality. In the process of nursing children with severe pneumonia, intensive care was provided, including condition assessment and diagnosis, close observation of disease, keeping the airway unblocked, rational oxygen therapy, prevention and treatment of respiratory and circulatory failure, support of vital organs, complications, and health education. The inflammatory response was proactively controlled, to prevent suffocation and reduce mortality. In summary, positive and effective nursing can promote the rehabilitation of children patients, which can be reinforced with adequate communication with the parents and/or caretakers.


id: cord-002757-upwe0cpj
author: Sullivan, Kathleen E.
date: 2017-08-07
txt: ./txt/cord-002757-upwe0cpj.txt
cache: ./cache/cord-002757-upwe0cpj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693703/
doi: 10.1007/s10875-017-0426-2
summary:
  The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. In developing countries where polio is still endemic and oral polio vaccine is essential for eradicating the disease, it is of utmost importance that all PIDD patients and family members should not receive live oral polio (OPV) because of the reported prolonged excretion of the virus for months and even years [24] . As for host factors, although severe and fatal cases have been described in healthy immunocompetent hosts [129, 130] , there is evidence to suggest that children under the age of 10 [130] and immunocompromised hosts either secondary to hematologic malignancies, immunosuppressant treatment for organ transplantation, or HIV infection are at a greater risk to develop more severe disease with higher case fatality rates [131, 132] .

title:
  Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies

abstract:
  In today’s global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text.


id: cord-004949-icsey27p
title: Contrasting Inflammatory Responses in Severe and Non-severe Community-acquired Pneumonia
author: Fernandez-Botran, Rafael
date: 2014-02-21
txt: ./txt/cord-004949-icsey27p.txt
cache: ./cache/cord-004949-icsey27p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087758/
doi: 10.1007/s10753-014-9840-2
summary:
  The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of proand anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. The objectives of this study were to characterize and contrast the lung and systemic cytokine profiles as well as blood neutrophil responses in patients with severe versus non-severe CAP at the time of hospital admission. In order to compare results of the plasma cytokines and neutrophil functional assays from CAP patients with those of healthy individuals, blood samples were also obtained from a control group (n=12) of healthy adult donors (approved by the University of Louisville′s IRB #191.06). Generally, patients in the severe CAP group showed a pattern with median plasma concentrations of both pro-and anti-inflammatory cytokines that were higher in comparison with the non-severe CAP group and the healthy control group.

abstract:
  The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI < 91 points) or severe (PSI ≥ 91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10753-014-9840-2) contains supplementary material, which is available to authorized users.


id: cord-005646-xhx9pzhj
author: nan
date: 1996
txt: ./txt/cord-005646-xhx9pzhj.txt
cache: ./cache/cord-005646-xhx9pzhj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095092/
doi: 10.1007/bf02316512
abstract: nan
summary:
  Aims and methods The aim of both a prospective and retrospective survey conducted in German pediatric intensive care units in 1993 was to accumulate data on the epidemiology, risk factors, natural history and treatment strategies in a large group of pediatric ARDS patients who were treated in the tt~ee year period from 1991 to 1993.All patients had acute bilateral alveolar infiltration of noncardiogenic origin and a pO2~iO2 ratio < 150mmHg. The influence of sex, underlying disease and single organ failure was analyzed using the Fischer''s exact test, the influence of additional organ failure on mortality was tested with the Cochran-Mantel-Haenszet statistics.

title:
  2nd World Congress on Pediatric Intensive Care 1996 Rotterdam, The Netherlands, 23–26 June 1996 Abstracts of Oral Presentations, Posters and Nursing Programme


id: cord-006448-elfroq6f
title: Severe adenovirus pneumonia in immunocompetent adults: a case report and review of the literature
author: Hakim, F. A.
date: 2007-11-21
txt: ./txt/cord-006448-elfroq6f.txt
cache: ./cache/cord-006448-elfroq6f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101838/
doi: 10.1007/s10096-007-0416-z
summary:
  We report a case of severe adenovirus pneumonia in a young immunocompetent male who presented with sudden onset respiratory distress that progressed rapidly to respiratory failure and made a successful recovery on supportive measures. Systematic review of the literature identified 14 cases of severe adenovirus pneumonia (defined as respiratory failure requiring ventilatory support at any point during the course of illness) in otherwise healthy immunocompetent adults both in epidemic and community settings. We report a case of severe adenovirus pneumonia in a previously healthy immunocompetent male who presented to us with rapidly developing respiratory failure and made a successful recovery on supportive measures. We defined severe adenovirus pneumonia if associated with respiratory failure requiring ventilatory support at any point during the course of illness and immunocompetent adults as individuals with no acquired or congenital immunodeficiency state with or without associated premorbid conditions.

abstract:
  Adenovirus is a frequent cause of mild self-limiting upper respiratory tract infection, gastroenteritis, and conjunctivitis in infants and young children. Fatal infections (severe pneumonia progressing to respiratory failure, septic shock and/or encephalitis) are rare among immunocompetent adults. We report a case of severe adenovirus pneumonia in a young immunocompetent male who presented with sudden onset respiratory distress that progressed rapidly to respiratory failure and made a successful recovery on supportive measures. Systematic review of the literature identified 14 cases of severe adenovirus pneumonia (defined as respiratory failure requiring ventilatory support at any point during the course of illness) in otherwise healthy immunocompetent adults both in epidemic and community settings. We describe the clinical characteristics, radiological features, and outcome of identified cases.


id: cord-007786-cu831tl7
title: Management of Severe Malaria and Severe Dengue in Resource-Limited Settings
author: Dondorp, Arjen M.
date: 2019-02-09
txt: ./txt/cord-007786-cu831tl7.txt
cache: ./cache/cord-007786-cu831tl7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123178/
doi: 10.1007/978-3-030-03143-5_9
summary:
  We suggest that in patients with hypotensive shock, fluid bolus therapy (30 mL/kg) with isotonic crystalloids be commenced (ungraded) and, if available, early initiation of vasopressor medication (ungraded) Timing of enteral feeding in cerebral malaria We suggest not to use a strategy of permissive hypercapnia to achieve ventilation with low tidal volumes in patients with cerebral malaria, because of the high incidence of brain swelling in these patients (ungraded) Fluid management in severe dengue We recommend not to use prophylactic platelet transfusion for thrombocytopenia in the absence of active bleeding complications or other risk factors (uncontrolled arterial hypertension, recent stroke, head trauma or surgery, continuation of an anticoagulant treatment, existing hemorrhagic diathesis) (1B) acidosis [14, 15] , and transpulmonary thermodilution-guided rapid fluid resuscitation resulted in pulmonary edema in 8/28 (29%) patients [15] . There are several randomized clinical trials comparing crystalloid with colloid fluid management for the treatment of patients with severe dengue and compensated shock.

abstract:
  This chapter summarizes recommendations on important aspects of the management of patients with severe malaria and severe dengue. Severe falciparum malaria requires rapid parasitological diagnosis by microscopy or rapid diagnostic test (RCT) and prompt initiation of parenteral artesunate. Fluid bolus therapy should be avoided in patients without hypotensive shock, and we suggest initial (24 h) crystalloid fluid therapy of 2–4 mL/kg/h, which may subsequently be reduced to 1 mL/kg/h in patients receiving additional fluids, e.g., through enteral tube feeding. In the minority of those patients presenting with hypotensive shock, we suggest fluid bolus therapy (30 mL/kg) with an isotonic crystalloid and early initiation of vasopressor support. Enteral feeding in non-intubated adult patients with cerebral malaria can start after 60 h, to avoid aspiration pneumonia. There are insufficient data to suggest this in pediatric cerebral malaria. The diagnosis of severe dengue is commonly with a combined dengue antigen (NS1) and antibody RDT. No antiviral treatment is currently available. Dengue shock results from capillary leakage, although hemorrhage or depression of myocardial contractility can contribute. The World Health Organization guidelines recommend restoration of the circulation guided by pulse pressure, capillary refill time, hematocrit, and urine output. Large (>15 mL/kg) rapid (<30 min) fluid boluses should be avoided, but prompt fluid administration with crystalloids is essential and should be restricted as soon as the critical phase is over to avoid pulmonary edema. Corticosteroids are not recommended, neither is platelet transfusion for thrombocytopenia in the absence of active bleeding or other risk factors.


id: cord-016057-efc6msf4
title: Severe Malaria: Manifestations, diagnosis, chemotherapy, and management of severe malaria in adults
author: Blumberg, Lucille
date: 2005
txt: ./txt/cord-016057-efc6msf4.txt
cache: ./cache/cord-016057-efc6msf4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120212/
doi: 10.1007/0-387-23380-6_1
abstract: nan
summary:
  In a confidential inquiry into malaria deaths in an area of South Africa with limited tertiary care facilities, major contributing factors were delays in diagnosis and initiation of adequate therapy, failure to administer the correct antimalarial at the correct dosage and frequency, inadequate monitoring of severity indicators in complicated cases, and the suboptimal management of complications (6). Some patients with severe malaria may have a negative smear due to sequestration of parasitised red blood cells, and a decision to treat with antimalarial chemotherapy should be considered if the index of suspicion is very high. The choice of chemotherapy for malaria is dependent on the severity of disease, the known or suspected resistance pattern of the parasite in the area where the malaria infection was acquired, the species of parasite, and patient profile (age, pregnancy, comorbidity, allergies, and medications, including any antimalarials recently administered). Acute renal failure in patients with severe falciparum malaria


id: cord-017715-99ri6x0y
title: SARS
author: Zhou, Bo-Ping
date: 2015-07-25
txt: ./txt/cord-017715-99ri6x0y.txt
cache: ./cache/cord-017715-99ri6x0y.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122356/
doi: 10.1007/978-94-017-7363-8_2
summary:
  2. The patient has been to or lived in areas reported with infectious SARS patients and patients suffering from secondary infections 2 weeks before the disease onset, who also have abovementioned clinical symptoms, not high peripheral blood white cell count and pulmonary shadows on chest X-ray fi lms. 3. The patient has been to or lived in areas reported with infectious SARS patients and patients suffering from secondary infections 2 weeks before the disease onset, who also have abovementioned clinical symptoms, pulmonary shadows on chest X-ray fi lms, and no obvious response to anti-infectious treatment. If the foci could not be absorbed for a long term in SARS recovery phase or patients still have symptoms but normal chest presentations, CT scan need to be carried out for further observation as it can better visualize the subtle pulmonary interstitial changes, such as lung interlobular septum thickening, intralobular septum thickening, subpleural linear shadow, and small ground-glassdensity lesion and regional and segmental bronchiectasis, and therefore is helpful for clinical diagnosis of pulmonary interstitial fi brosis.

abstract:
  Severe acute respiratory syndrome (SARS) is an acute respiratory tract infectious disease induced by SARS-CoV and mainly transmitted through the short-distance air droplets and close contact. Its main clinical characteristics is abrupt onset of the disease and the initial symptom is fever accompanied with systematic symptoms of headache, soreness and fatigue, and respiratory tract symptoms such as cough, chest dullness, and dyspnea. A few cases may progress to acute respiratory distress syndrome (ARDS). Due to its self-limiting feature, the prognosis is predominantly good but may be poor in severe cases, with mortality about 9.3 %. Some patients may develop such complications such as lung fibrosis and necrosis of the head of femur. On April 8, 2003, SARS was defined as a legal infectious disease by the Ministry of Heath of China.


id: cord-017758-zfudssm9
title: Emergence of New Tickborne Infections
author: Fong, I. W.
date: 2017-02-08
txt: ./txt/cord-017758-zfudssm9.txt
cache: ./cache/cord-017758-zfudssm9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122411/
doi: 10.1007/978-3-319-50890-0_5
summary:
  These include new phleboviruses of the Bunyaviridae family, exemplified by severe fever with thrombocytopenia syndrome virus [SFTSV] recognized in China in 2010, and the Heartland virus, a closely related but distinct virus, presenting with similar clinical features and discovered in Missouri in 2012. Other newly recognized tickborne infections include a novel spirochete of the relapsing fever group, Borrelia miyamotoi, first reported to cause human infection in Russia in 2011 and subsequently discovered to cause clinical disease in the Netherlands, Japan, and the United States, with transmission by the black-legged deer tick Ixodes scapularis. Transmission of SFTSV is considered mainly from tick bites, but there is also evidence from multiple reports that the virus can be transmitted from human to human by direct contact with blood of infected patients [67] [68] [69] [70] [71] . Severe fever with thrombocytopenia syndrome virus in ticks collected from humans, South Korea

abstract:
  Several tickborne infectious diseases such as Lyme borreliosis, ehrlichiosis, anaplasmosis, babesiosis, and others have been expanding to new endemic regions in the world for over a decade. Moreover, new pathogens transmitted by ticks have recently been recognized in animals and humans from diverse regions of the globe, widely separated in distance. These include new phleboviruses of the Bunyaviridae family, exemplified by severe fever with thrombocytopenia syndrome virus [SFTSV] recognized in China in 2010, and the Heartland virus, a closely related but distinct virus, presenting with similar clinical features and discovered in Missouri in 2012. Other newly recognized tickborne infections include a novel spirochete of the relapsing fever group, Borrelia miyamotoi, first reported to cause human infection in Russia in 2011 and subsequently discovered to cause clinical disease in the Netherlands, Japan, and the United States, with transmission by the black-legged deer tick Ixodes scapularis. In Europe a new tickborne disease, neoehrlichiosis caused by Candidatus neoehrlichia mikurensis belonging to the Anaplasmataceae family, has been described recently. Furthermore, new tickborne rickettsial infections continue to be recognized in Europe such as tickborne lymphadenopathy identified in 1997 and caused by Rickettsia slovaca. Novel tickborne infectious diseases will continue to emerge worldwide for the foreseeable future and be a challenge to the health of human populations. Innovative methods of prevention for a broad variety of tick-transmitted diseases are needed, and one approach is to develop a universal tick vaccine that can be given to animal hosts or humans.


id: cord-017870-5fu4uswq
title: Falciparum Malaria
author: Feldman, C.
date: 2010-05-20
txt: ./txt/cord-017870-5fu4uswq.txt
cache: ./cache/cord-017870-5fu4uswq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122550/
doi: 10.1007/978-3-540-34406-3_24
summary:
  Studies of outcome of patients with falciparum malaria in the intensive care unit (ICU) commonly report that markers of severity of illness (such as the SAPS or APACHE II score), shock, acidosis, coma, pulmonary edema and coagulation disorders are indicators of poor outcome [21] . On the other hand studies have suggested that HIV infection may be significantly associated with the development of severe and complicated malaria [24] , being associated with a high parasite burden with the associated risk that this may potentially lead to poor malaria control and a greater chance for the development of resistance to anti-malarial agents [26] . Studies in children recovering from cerebral malaria have shown neurological sequelae in approximately 10 % or more of cases and these occur especially with infections that were complicated by hypoglycemia [3, 7] .

abstract:
  Malaria is one of the most common infectious diseases in the world today, being the most important parasitic infection, and Plasmodium falciparum is the organism responsible for most of the mortality [1]. It has been estimated that approximately 300–500 million people contract malaria every year, with approximately 1–2 million deaths, most of these occurring in children [1–5]. Plasmodium falciparum, Mycobacterium tuberculosis and measles currently compete for the title of the single most important pathogen causing human morbidity and mortality [2, 3]. Infection with Plasmodium falciparum has a wide variety of potential clinical consequences [4, 6, 7].


id: cord-018764-02l423mk
title: The molecular basis of paediatric malarial disease
author: Clark, Ian A.
date: 2007
txt: ./txt/cord-018764-02l423mk.txt
cache: ./cache/cord-018764-02l423mk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123729/
doi: 10.1007/978-3-7643-8099-1_9
summary:
  The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process. The presence of hyperlactataemia, hypoglycaemia, and metabolic acidosis, all three consistent with a patient being forced to rely on anaerobic glycolysis for energy production, have provided a consensus that hypoxia is central to disease pathogenesis in falciparum malaria. Another inflammatory cytokine, macrophage inhibitory factor (MIF) that is increased in malaria, and induced by TNF, has been shown to cause dyserythropoiesis in in vitro studies on bone marrow cells [95, 96] . Although the sepsis world now discusses several origins for the lactate increase, including inflammation-induced mitochondrial dysfunction [97] , in falciparum malaria it is still generally attributed to a reduced oxygen supply, mostly through microvascular occlusion by sequestered parasitised erythrocytes [121] .

abstract:
  Severe falciparum malaria is an acute systemic disease that can affect multiple organs, including those in which few parasites are found. The acute disease bears many similarities both clinically and, potentially, mechanistically, to the systemic diseases caused by bacteria, rickettsia, and viruses. Traditionally the morbidity and mortality associated with severe malarial disease has been explained in terms of mechanical obstruction to vascular flow by adherence to endothelium (termed sequestration) of erythrocytes containing mature-stage parasites. However, over the past few decades an alternative ‘cytokine theory of disease’ has also evolved, where malarial pathology is explained in terms of a balance between the pro- and anti-inflammatory cytokines. The final common pathway for this pro-inflammatory imbalance is believed to be a limitation in the supply and mitochondrial utilisation of energy to cells. Different patterns of ensuing energy depletion (both temporal and spatial) throughout the cells in the body present as different clinical syndromes. This chapter draws attention to the over-arching position that inflammatory cytokines are beginning to occupy in the pathogenesis of acute malaria and other acute infections. The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process.


id: cord-023169-obupqcua
title: Leptospirosis
author: Chierakul, Wirongrong
date: 2013-10-21
txt: ./txt/cord-023169-obupqcua.txt
cache: ./cache/cord-023169-obupqcua.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167526/
doi: 10.1016/b978-0-7020-5101-2.00038-8
abstract: nan
summary:
  The severe illness, characterized by febrile illness with jaundice, acute renal injury and bleeding, is recognized as Weil''s disease, though many different local names have been used such as Fort Bragg, mud, swamp and sugar cane fevers. Complications such as cholestatic jaundice, aseptic meningitis, acute renal injury, haemorrhage especially in the lung and myocarditis can occur and lead to a fatal outcome. 24 Complications such as jaundice, acute renal injury, haemorrhage, especially pulmonary haemorrhage, aseptic meningitis, myocarditis, shock, occur early during the course of illness. Acute pancreatitis has been reported rarely, although serum amylase may be raised in up to 60% of patients with severe disease due to renal impairment. Nowadays, the term ''Weil''s syndrome'' usually refers to the extremely severe form of leptospirosis, characterized by the combination of jaundice, renal dysfunction, and haemorrhagic diathesis, especially pulmonary haemorrhage. Acute febrile illness accompanied by jaundice and renal failure should always include leptospirosis in the differential diagnosis.


id: cord-026031-hnf5vayd
title: Emergency Care
author: Ford, Richard B.
date: 2009-05-21
txt: ./txt/cord-026031-hnf5vayd.txt
cache: ./cache/cord-026031-hnf5vayd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271342/
doi: 10.1016/b0-72-160138-3/50002-3
abstract: nan
summary:
  Fresh whole blood Coagulopathy with active hemorrhage (disseminated intravascular coagulation, thrombocytopenia; massive acute hemorrhage; no stored blood available) Stored whole blood Massive acute or ongoing hemorrhage; hypovolemic shock caused by hemorrhage that is unresponsive to conventional crystalloid and colloid fluid therapy; unavailability of equipment required to prepare blood components Packed red blood cells Nonregenerative anemia, immune-mediated hemolytic anemia, correction of anemia before surgery, acute or chronic blood loss Fresh frozen plasma Factor depletion associated with active hemorrhage (congenital: von Willebrand''s factor, hemophilia A, hemophilia B; acquired: vitamin K antagonist, rodenticide intoxication, DIC); acute or chronic hypoproteinemia (burns, wound exudates, body cavity effusion; hepatic, renal, or gastrointestinal loss); colostrum replacement in neonates Frozen plasma Acute plasma or protein loss; chronic hypoproteinemia; (contains stable colostrum replacement in neonates; hemophilia B and clotting factors) selected clotting factor deficiencies Platelet-rich plasma* Thrombocytopenia with active hemorrhage (immune-mediated thrombocytopenia, DIC); platelet function abnormality (congenital: thrombasthenia in Bassett hounds; acquired: NSAIDs, other drugs) Cryoprecipitate


id: cord-026653-094bk0t0
author: Gülsen, Askin
date: 2020-06-24
txt: ./txt/cord-026653-094bk0t0.txt
cache: ./cache/cord-026653-094bk0t0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289641/
doi: 10.1007/s15007-020-2550-1
summary:
  This review will evaluate reports of allergic and substance-specific infusion reactions (IR), injection-site reactions (ISR), hypersensitivity reactions (HSR), urticaria, and anaphylaxis caused by BSs. The most common indications for the use of biologics in lung diseases are allergic and severe uncontrolled asthma. The Australian Public Assessment report and the FDA label did not observe an increase in the incidence of severe immunological and anaphylactic reactions related to the use of nintedanib [25, 26] . According to the recent BCCA Drug Manual, it was reported that HSR including anaphylaxis can develop in ≤ 1 % (severe < 1 %), IRs in 1 % (severe ≤ 1 %), and immune-mediated rash in 8-18 % ( severe ≤ 1 %) of patients [58] . The FDA''s 2019 label reported infusion-related reactions in 11-24 % of patients (placebo 7-18.0 %), acute urticaria in 1-2 %, acute HSRs in 1.5 %, pruritus in 4 %, and serious IRs and anaphylaxis in < 1 % [159] .

title:
  Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

abstract:
  Purpose: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. Methods: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. Results: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). Conclusion: There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future. Cite this as Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events. Allergo J Int 2020; 29:97-125 https://doi.org/10.1007/s40629-020-00126-6


id: cord-030369-4dn02a35
title: Clinical Manifestations and Laboratory Tests of AECHB and Severe Hepatitis (Liver Failure)
author: Peng, Liang
date: 2019-05-21
txt: ./txt/cord-030369-4dn02a35.txt
cache: ./cache/cord-030369-4dn02a35.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418529/
doi: 10.1007/978-94-024-1603-9_1
summary:
  Once pulmonary infection is present, the disease condition will likely deteriorate, directly causing death; (3) a majority of infections are nosocomial infection, and pathogens are usually resistant to common antibiotics, making therapy challenging; (4) the pathogens causing infection are diverse but mainly Gram-negative bacteria, although the incidence of Gram-positive and fungal infections is increasing; (5) infection is closely related to the prognosis for liver failure patients. Although their clinical manifestation differ significantly, the "coexistence of acute and chronic failures" is shared by failures of all those organs; (2) CLF classification has been generally recognized at home and abroad, and the necessity of classification are further proved by the difference between CLF and the other three types; (3) CLF cases are relatively large in proportion (nearly 30%), which is still increasing (since the proportion of ALF/SALF are lowering); (4) Complications of CLF are common and are found in various forms, with bad prognosis; (5) In CLF patients with correlation to HBV, virus replication are commonly found, which is closely related to decompensation.

abstract:
  This chapter describes the clinical symptoms and signs of AECHB and HBV ACLF, classification, grading of HBV ACLF and their features, diagnostic principles and standards in liver pathology, biochemistry, and virology of HBV ACLF. 1. Liver failure is defined as serious damage to the liver cause by a variety of etiologies, leading to liver function disorder or even decompensation, and clinical syndromes with coagulopathy, jaundice, hepatic encephalopathy, and ascites. 2. Severe hepatitis B can be indicated pathologically by apparent hepatocellular necrosis, including extensive multifocal, confluent, bridging, sub-massive or massive necrosis. 3. Laboratory tests during the course of severe exacerbation of chronic hepatitis B can reflect pathological changes and liver function in a timely manner, providing objective and informative reference data for evaluation of disease severity and treatment efficacy. Among the most important laboratory tests are those for prothrombin activity, international normalized ratio, and increases in total bilirubin concentration. 4. Severe hepatitis B is associated with interactions between the virus and host factors. Detection of HBV DNA, HBV genotype, quasispecies and HBV mutation can provide important theoretical bases for the prevention, control or mitigation of the progress of severe hepatitis B. 5. Noninvasive imaging modalities can be used to visualize the entire liver and parts of it. Measuring liver volume to evaluate liver size and liver reserve capacity is regarded as important in diagnosis, surgical approach and prognostic evaluation of patients with severe exacerbation of chronic hepatitis B and liver failure. 6. Model for End-Stage Liver Disease (MELD) is the first quantitative method developed to assess whether a patient with liver failure requires a liver transplant. The predictive value of the MELD model has been improved by the MELD-Na, iMELD, and MESO models. Several other valuable prognostic models have been developed. For example, for patients with HBV-ACLF, the established TPPM scoring system was found to be more predictive than MELD score.


id: cord-032181-gmcugd8h
title: Main Complications of AECHB and Severe Hepatitis B (Liver Failure)
author: Song, Jian-Xin
date: 2019-05-21
txt: ./txt/cord-032181-gmcugd8h.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498917/
doi: 10.1007/978-94-024-1603-9_2
summary:
  3. Hepatorenal syndrome, which is characterized by renal failure, hemodynamic changes in arterial circulation and abnormalities in the endogenous vascular system, is a common clinical complication of end-stage liver disease, and one of the important indicators for the prognosis of patients with severe hepatitis. The latest report indicated that basic laboratory examinations for coagulation function testing in common use at present, such as PT, APTT, international normalized ratio (INR) etc., have little correlation with occurrence of gastrointestinal bleeding in these patients, thereby revealing the importance to search and pay close attention to those complicating disease upregulating bleeding risk, such as bacterial infection, renal failure, hemodynamic change after portal hypertension, dysfunction of endotheliocyte as well as macrophagocyte and so on [107] .

abstract:
  This chapter describes the clinical features, and diagnosis of complications in AECHB including secondary bacterial infections, coagulation disorder, water electrolyte disorder, hepatorenal syndrome, hepatic encephalopathy, hepatopulmonary syndrome and endotoxemia: 1. Patients with severe hepatitis have impaired immunity and are therefore vulnerable to all kinds of infections. After infection, these patients may experience shock, DIC and multiple organ failure, all of which seriously affect their prognosis and are major causes of death. Concurrent infections consist primarily of infections of the lungs, intestines, biliary tract, and urinary tract, as well as spontaneous bacterial peritonitis and sepsis. 2. Severe hepatitis may reduce the synthesis of coagulation factors and enhance their dysfunction and increase anticoagulants and platelet abnormalities, leading to coagulopathy. Infection, hepatorenal syndrome and complications can further aggravate coagulopathy, resulting in DIC and seriously affecting patient prognosis. 3. Hepatorenal syndrome, which is characterized by renal failure, hemodynamic changes in arterial circulation and abnormalities in the endogenous vascular system, is a common clinical complication of end-stage liver disease, and one of the important indicators for the prognosis of patients with severe hepatitis. 4. Water electrolyte disorder (water retention, hyponatremia, hypokalemia, hyperkalaemia) and acid-base imbalance are common in patients with severe hepatitis. These internal environment disorders can lead to exacerbation and complication of the illness. 5. Hepatic encephalopathy is a neurological and psychiatric anomaly syndrome based on metabolic disorder, and an important prognostic indicator for patients with severe hepatitis. 6. The hepatopulmonary syndrome is an important vascular complication in lungs due to systemic hypoxemia in patients with cirrhosis and portal hypertension. The majority of patients with HPS are asymptomatic. Long-term oxygen therapy remains the most frequently recommended therapy for symptoms in patients with severe hypoxemia. 7. Endotoxemia, an important complication of severe hepatitis, is not only a second hit to the liver, but also leads to other complications including SIRS and MODS.


id: cord-033833-woref5g8
author: Fragoso-Saavedra, Sergio
date: 2020-10-16
txt: ./txt/cord-033833-woref5g8.txt
cache: ./cache/cord-033833-woref5g8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563903/
doi: 10.1186/s12879-020-05485-7
summary:
  title: A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol METHODS: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. Exclusion criteria include one or more of the following: allergy to pyridostigmine; pregnancy or breastfeeding status; concomitant autoimmune disease; diagnosed immunodeficiencies (including HIV infection); need for mechanical ventilation, admission to the ICU, or meeting criteria for septic shock before providing signed, informed consent; inability to receive orally or enterally administered drugs; use of immunosuppressants or immune-modulators (including chemotherapy and corticosteroids) in the preceding 28-day period unless recommended by the treatment medical team as part of the therapeutic approach for SARS-CoV-2 infection; and participation in clinical trials of any kind in the previous 28 days.

title:
  A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol

abstract:
  BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. METHODS: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. DISCUSSION: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).


id: cord-035020-mhs7yext
author: Simadibrata, Daniel Martin
date: 2020-11-02
txt: ./txt/cord-035020-mhs7yext.txt
cache: ./cache/cord-035020-mhs7yext.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649648/
doi: 10.1177/1751143720969587
summary:
  title: Platelet-to-lymphocyte ratio, a novel biomarker to predict the severity of COVID-19 patients: A systematic review and meta-analysis Research articles comparing the PLR value on admission in adult patients with COVID-19 with varying degrees of severity were included in the analysis. Therefore, this systematic review aims to review the prognostic value of PLR levels on admission to determine the severity and mortality of COVID-19 patients. We included cohort studies evaluating the difference in PLR levels on admission in adults (>18 years old) with confirmed COVID-19 (diagnosed using RT-PCR) categorized based on disease severity (severe and non-severe patients), and/or mortality (survivor and non-survivor). Our meta-analysis, which included a total of 998 COVID-19 patients, showed that high PLR value was associated with severe COVID-19. Six out of the seven included studies demonstrated similar results with increased PLR on admission found in severe cases of COVID-19 compared to those with mild or moderate diseases.

title:
  Platelet-to-lymphocyte ratio, a novel biomarker to predict the severity of COVID-19 patients: A systematic review and meta-analysis

abstract:
  Platelet-to-lymphocyte ratio (PLR), a novel inflammatory marker, has been suggested to predict the severity of COVID-19 patients. This systematic review aims to evaluate the association between PLR levels on admission and the severity of COVID-19 patients. A systematic literature search was done on 23 July 2020 to identify peer-reviewed studies, preprints, and grey literatures. Research articles comparing the PLR value on admission in adult patients with COVID-19 with varying degrees of severity were included in the analysis. The following keywords were used for the search: “COVID-19”, “PLR”, “severity”, and “mortality”. A total of seven studies were included in the meta-analysis, six of which were conducted in China. From a total of 998 participants included, 316 (31.7%) had severe diseases; and those in the severe group were generally older and had underlying diseases compared to the non-severe group. In comparison to non-severe patients, the meta-analysis showed that severe COVID-19 patients had higher PLR levels on admission (SMD 0.68; 95%CI 0.43-0.93; I(2) =58%). High PLR levels on admission were associated with severe COVID-19 cases. Therefore, the on-admission PLR level is a novel, cost-effective, and readily available biomarker with a promising prognostic role for determining the severity of COVID-19 patients.


id: cord-253077-61fmul8c
title: Immunology of COVID-19: current state of the science
author: Vabret, Nicolas
date: 2020-05-06
txt: ./txt/cord-253077-61fmul8c.txt
cache: ./cache/cord-253077-61fmul8c.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32505227/
doi: 10.1016/j.immuni.2020.05.002
summary:
  Lastly, Nonhuman primate (NHP) studies and patient data on SARS-CoV-1 have also shown that virus spike-specific IgG responses can exacerbate acute lung injury due to repolarization of alveolar macrophages into pro-inflammatory phenotypes and enhanced recruitment of inflammatory monocyte via CCL2 and IL-8 (Clay et al., 2012; Liu et al., 2019) . Collectively, these data suggest that cross-talk with monocytes might impair NK cell recognition and killing of SARS-CoV-2infected cells, and antibodies targeting IL-6 and TNF-signaling may benefit enhanced NK cell functions in COVID-19 patients ( Figure 2 ). However, these CD4 T cells lacked phenotypic markers of activation and were specific for C-terminal S protein epitopes that are highly similar to endemic human coronaviruses, suggesting that crossreactive CD4 memory T cells in some populations (e.g., children and younger patients that experience a higher incidence of hCoV infections) may be recruited into an amplified primary SARS-CoV-2-specific response (Braun et al., 2020) .

abstract:
  Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.


id: cord-253502-v2hh3w3r
author: Leung, C.W.
date: 2004-11-05
txt: ./txt/cord-253502-v2hh3w3r.txt
cache: ./cache/cord-253502-v2hh3w3r.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S152605420400079X
doi: 10.1016/j.prrv.2004.07.010
summary:
  authors: Leung, C.W.; Chiu, W.K. title: Clinical picture, diagnosis, treatment and outcome of severe acute respiratory syndrome (SARS) in children [5] [6] [7] [8] [9] [10] [11] Superspreading events including a major hospital outbreak, in-flight transmission on board commercial PAEDIATRIC RESPIRATORY REVIEWS (2004) Summary Children are susceptible to infection by SARS-associated coronavirus (SARS-CoV) but the clinical picture of SARS is milder than in adults.

title:
  Clinical picture, diagnosis, treatment and outcome of severe acute respiratory syndrome (SARS) in children

abstract:
  Children are susceptible to infection by SARS-associated coronavirus (SARS-CoV) but the clinical picture of SARS is milder than in adults. Teenagers resemble adults in presentation and disease progression and may develop severe illness requiring intensive care and assisted ventilation. Fever, malaise, cough, coryza, chills or rigor, sputum production, headache, myalgia, leucopaenia, lymphopaenia, thrombocytopaenia, mildly prolonged activated partial thromboplastin times and elevated lactate dehydrogenase levels are common presenting features. Radiographic findings are non-specific but high-resolution computed tomography of the thorax in clinically suspected cases may be an early diagnostic aid when initial chest radiographs appear normal. The improved reverse transcription-polymerase chain reaction (RT-PCR) assays are critical in the early diagnosis of SARS, with sensitivity approaching 80% in the first 3 days of illness when performed on nasopharyngeal aspirates, the preferred specimens. Absence of seroconversion to SARS-CoV beyond 28 days from disease onset generally excludes the diagnosis. The best treatment strategy for SARS among children remains to be determined. No case fatality has been reported in children and the short- to medium-term outcome appears to be good. The importance of continued monitoring for any long-term complications due to the disease or its empiric treatment, cannot be overemphasised.


id: cord-254419-qw83atrx
author: Bhattacharyya, Rajat
date: 2020-08-25
txt: ./txt/cord-254419-qw83atrx.txt
cache: ./cache/cord-254419-qw83atrx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s41030-020-00126-5
doi: 10.1007/s41030-020-00126-5
summary:
  This narrative review aims to summarize the current available evidence on the interplay between hypercoagulability, thrombo-inflammation, and pulmonary microvascular thrombosis in COVID-19 infection resulting in respiratory failure and how this information can be used to design clinical trials to optimize patient outcomes. ACE2 angiotensin-converting enzyme 2, CRP C-reactive protein, ESR erythrocyte sedimentation rate, LDH lactate dehydrogenase, NETS neutrophil extracellular traps, SARS-COV-2 severe acute respiratory syndrome coronavirus 2, TMPRSS2 transmembrane protease serine 2 shown to be at higher risk of worse outcomes [13] [14] [15] (Fig. 2) . CHD chronic heart disease, CLD chronic lung disease, CKD chronic kidney disease, DOACS direct oral anticoagulants, FDPs fibrinogen degradation products, HTN hypertension, IFN interferon, JAK Janus kinase, LDH lactate dehydrogenase, LMWH low molecular weight heparin, NSAIDS nonsteroidal anti-inflammatory drugs, PT prothrombin time, TNF tumor necrosis factor, VW Ag Von Willebrand antigen and microvascular thrombosis appears to be responsible for the clinical picture that leads to progressive multi-organ failure in a small percentage of patients, ultimately causing fatalities.

title:
  The Interplay Between Coagulation and Inflammation Pathways in COVID-19-Associated Respiratory Failure: A Narrative Review

abstract:
  The novel coronavirus disease (COVID-19) pandemic has caused an unprecedented worldwide socio-economic and health impact. There is increasing evidence that a combination of inflammation and hypercoagulable state are the main mechanisms of respiratory failure in these patients. This narrative review aims to summarize currently available evidence on the complex interplay of immune dysregulation, hypercoagulability, and thrombosis in the pathogenesis of respiratory failure in COVID-19 disease. In addition, we will describe the experience of anticoagulation and anti-inflammatory strategies that have been tested. Profound suppression of the adaptive and hyperactivity of innate immune systems with macrophage activation appears to be a prominent feature in this infection. Immune dysregulation together with endotheliitis and severe hypercoagulability results in thromboinflammation and microvascular thrombosis in the pulmonary vasculature leading to severe respiratory distress. Currently, some guidelines recommend the use of prophylactic low molecular weight heparin in all hospitalized patients, with intermediate dose prophylaxis in those needing intensive care, and the use of therapeutic anticoagulation in patients with proven or suspected thrombosis. Strong recommendations cannot be made until this approach is validated by trial results. To target the inflammatory cascade, low-dose dexamethasone appears to be helpful in moderate to severe cases and trials with anti-interleukin agents (e.g., tocilizumab, anakinra, siltuximab) and non-steroidal anti-inflammatory drugs are showing early promising results. Potential newer agents (e.g., Janus kinase inhibitor such as ruxolitinib, baricitinib, fedratinib) are likely to be investigated in clinical trials. Unfortunately, current trials are mostly examining these agents in isolation and there may be a significant delay before evidence-based practice can be implemented. It is plausible that a combination of anti-viral drugs together with anti-inflammatory and anti-coagulation medicines will be the most successful strategy in managing severely affected patients with COVID-19.


id: cord-254809-o454k6ae
title: The Metabolic Changes and Immune Profiles in Patients With COVID-19
author: He, Bing
date: 2020-08-28
txt: ./txt/cord-254809-o454k6ae.txt
cache: ./cache/cord-254809-o454k6ae.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.02075
doi: 10.3389/fimmu.2020.02075
summary:
  Third, according to an analysis of nearly 45,000 confirmed cases, 19% of patients with COVID-19 have been identified as severe cases and critically ill cases, involving severe pneumonia and metabolic disorders, developing into acute respiratory distress syndrome (ARDS), multiple organ dysfunctions (MODS), and even septic shock and death (9, 12) . In this study, we investigated mild cases and severe cases infected with SARS-CoV-2, as well as healthy young children and adults. Our study suggests that monocytes, neutrophils, and T-lymphocytes are associated with the onset and progress of COVID-19 infection, and immunopathogenesis was involved in ARDS, metabolic disorders, and MODS in severe cases. We collected the data of patients with COVID-19, including the clinical records, laboratory results and chest computed tomography (CT) scan images of mild and severe cases in the hospital. Extremely high levels of circulating lymphocytes and monocytes would benefit to fight against SARS-CoV-2 infection, which might be associated with the low morbidity of COVID-19 in young children.

abstract:
  To explore the metabolic changes and immune profiles in patients with COVID-19, we analyzed the data of patients with mild and severe COVID-19 as well as young children with COVID-19. Of the leukocytes, 47% (IQR, 33–59) were lymphocytes [2.5 × 10(9)/L (IQR, 2.2–3.3)], and monocytes were 0.51 × 10(9)/L (IQR, 0.45–0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45 × 10(9)/L (IQR, 0.36–0.64). Twenty-one severe patients had low PO(2) [57 mmHg (IQR, 50–73)] and SO(2) [90% (IQR, 86–93)] and high lactate dehydrogenase [580 U/L (IQR, 447–696)], cardiac troponin I [0.07 ng/mL (IQR, 0.02–0.30)], and pro-BNP [498 pg/mL (IQR, 241–1,726)]. Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62–22.85) and 32.7 mg/L (IQR, 12.8–81.9), and a large number of RBC (46/μL (IQR, 4–242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose [7.4 mmol/L (IQR, 5.9–10.1)]. Fifteen of 21 (71%) severe cases had urine glucose +, and nine of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption of cells. Severe cases had extraordinarily low serum uric acid [176 μmol/L (IQR, 131–256)]. In the late stage of COVID-19, severe cases had extremely low CD4(+) T cells and CD8(+) T cells, but unusually high neutrophils [6.5 × 10(9)/L (IQR, 4.8–9.6)], procalcitonin [0.27 ng/mL (IQR, 0.14–1.94)], C-reactive protein [66 mg/L (IQR, 25–114)] and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and two of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) I–III, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19.


id: cord-255174-h1izji2g
title: Risk factors for severe COVID-19: evidence from 167 hospitalized patients in Anhui, China
author: Wei, Yuan-Yuan
date: 2020-04-17
txt: ./txt/cord-255174-h1izji2g.txt
cache: ./cache/cord-255174-h1izji2g.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S016344532030219X?v=s5
doi: 10.1016/j.jinf.2020.04.010
abstract: nan
summary:
  It is very important to analyse the clinical characteristics of COVID-19 in international regions and identify risk factors to reduce the incidence of severe and critical illness in the early stage. In this letter, we present discrepancies of patients with different disease severities and risk factors for severe COVID-19 by comparing and analysing epidemiological and clinical data of 167 confirmed patients in Anhui, China. There are still no specific therapies for COVID-19(1); nevertheless, assessing risk factors and symptomatic treatment in the early stage of the disease can improve the prognosis. The similarities and differences between severe and non-severe patients in this letter suggested that elderly patients with multiple comorbidities, hypoxia, decreased CD4 and CD8 cell counts and increased levels of CRP and IL-6 are all closely associated with disease severity and prognosis, which should be assessed seriously during diagnosis and treatment. MDT consultation and artificial liver therapy are very effective methods for severe patients with COVID-19.


id: cord-255490-gyq6cpc9
title: Early risk factors of the exacerbation of Coronavirus disease 2019 pneumonia
author: Wang, Chang‐Zheng
date: 2020-05-29
txt: ./txt/cord-255490-gyq6cpc9.txt
cache: ./cache/cord-255490-gyq6cpc9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32470167/
doi: 10.1002/jmv.26071
summary:
  Restrospective analysis of clinical data of 85 patients infected with SARS‐CoV‐2, including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest CT. Severe patients often develop dyspnea and/or hypoxemia one week after onset, and may even rapidly progress to acute respiratory distress syndrome (ARDS), septic shock, hard-to-correct metabolic acidosis, bleeding and coagulation dysfunction, and multiple organ failure 2 . The clinical data of 85 patients diagnosed by COVID-19 were collected, including 39 common patients in department of infectious diseases from January 10, 2020 to February 15, 2020 and 46 severe and critical patients in intensive care unit (ICU) from January 10, 2020 to February 28, 2020. In addition, in terms of comorbidities, compared with common patients, the proportion of severe and critical patients with hypertension (13.0% vs 41.0%, p=0.003) and coronary heart disease (2.2% vs 20.5%, p=0.017) were higher.

abstract:
  The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID‐19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with SARS‐CoV‐2, including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest CT. All laboratory examination were measured within first 24 hours after admission, and chest CT were performed before admission. 56 (65.9%) patients had a history of exposure to Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID‐2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (p=0.003) and coronary heart disease (p=0.017). All severe and critical patients infected with SARS‐CoV‐2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (p<0.001). Severe and critical patients showed higher WBC count (p=0.006), NEU count (p=0.001), NEU% (p=0.002), PCT (p=0.011), CRP (p=0.003), PT (p=0.035), D‐dimer (p=0.025), AST (p=0.006), and lower LYM count (p=0.019), LYM% (p=0.001), ALB (p<0.001). Logistic regression analysis showed NEU count is a independent risk factor for deterioration, with the threshold of 6.5×10(9)·L(‐1). We concluded that the laboratory independent risk factor for the progression of COVID‐19 pneumonia is NEU count. In addition, COVID‐19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease. This article is protected by copyright. All rights reserved.


id: cord-257344-d13at1y5
author: Ghasemiyeh, Parisa
date: 2020-09-18
txt: ./txt/cord-257344-d13at1y5.txt
cache: ./cache/cord-257344-d13at1y5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32980626/
doi: 10.1016/j.hrtlng.2020.08.025
summary:
  Patients with predisposing diseases are highly prone to COVID-19 and manifesting severe infection especially with organ function damage such as acute respiratory distress syndrome, acute kidney injury, septic shock, ventilator-associated pneumonia, and death. Patients with underlying diseases are highly prone to present with severe infection especially with organ function damage such as acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), septic shock, and ventilator-associated pneumonia (VAP) 10, 13 . Results of another systematic review and meta-analysis on 53 randomized clinical trials on administration of hydroxychloroquine in COVID-19 management revealed that hydroxychloroquine administration (case group) was significantly associated with higher incidence of total adverse effects in comparison to placebo or no treatment (control group) in overall population of patients with COVID-19 45 . Almost all of the potential drugs in COVID-19 treatment containing chloroquine, hydroxychloroquine, ribavirin, and lopinavir/ritonavir have hepatic metabolism.

title:
  COVID-19 Outbreak: Challenges in Pharmacotherapy Based on Pharmacokinetic and Pharmacodynamic Aspects of Drug Therapy in Patients with Moderate to Severe Infection

abstract:
  The new coronavirus (COVID-19) was first detected in Wuhan city of China in December 2019. Most patients infected with COVID-19 had clinical presentations of dry cough, fever, dyspnea, chest pain, fatigue and malaise, pneumonia, and bilateral infiltration in chest CT. Soon COVID-19 was spread around the world and became a pandemic. Now many patients around the world are suffering from this disease. Patients with predisposing diseases are highly prone to COVID-19 and manifesting severe infection especially with organ function damage such as acute respiratory distress syndrome, acute kidney injury, septic shock, ventilator-associated pneumonia, and death. Till now many drugs have been considered in the treatment of COVID-19 pneumonia, but pharmacotherapy in elderly patients and patients with pre-existing comorbidities is highly challenging. In this review, different potential drugs which have been considered in COVID-19 treatment have been discussed in detail. Also, challenges in the pharmacotherapy of COVID-19 pneumonia in patients with the underlying disease have been considered based on pharmacokinetic and pharmacodynamic aspects of these drugs.


id: cord-258307-nsdhvc8w
author: Maki, Dennis G.
date: 2011-10-20
txt: ./txt/cord-258307-nsdhvc8w.txt
cache: ./cache/cord-258307-nsdhvc8w.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0025619611621812
doi: 10.4065/79.11.1359
abstract: nan
summary:
  The most recent and perhaps most fearsome emerging infections are the appearance of West Nile virus encephalitis in New York City in 1999 and its rapid spread westward 6 ; inhalation anthrax, deriving from use of Bacillus anthracis spores as a biologic weapon against the US civilian population in 2001 7 ; the global outbreak of severe acute respiratory syndrome (SARS) in 2003 8 ; and the looming threat of pandemic influenza, especially global disease caused by the highly virulent avian subtype A (H5N1). If it is not, the effort will not have been wasted because it is likely that all the planning and resource allocation will prove invaluable for controlling the spread of natural emerging pathogens, such as SARS-CoV or a new strain of influenza virus, which are probably far more likely to pose a serious threat to human and animal health in the United States and worldwide.

title:
  SARS Revisited: The Challenge of Controlling Emerging Infectious Diseases at the Local, Regional, Federal, and Global Levels


id: cord-260238-2p209g2p
title: Severe acute respiratory syndrome
author: Peiris, J S M
date: 2004-11-30
txt: ./txt/cord-260238-2p209g2p.txt
cache: ./cache/cord-260238-2p209g2p.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/15577937/
doi: 10.1038/nm1143
summary:
  Severe acute respiratory syndrome (SARS) was caused by a previously unrecognized animal coronavirus that exploited opportunities provided by ''wet markets'' in southern China to adapt to become a virus readily transmissible between humans. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS CoV) in SARS patients: implications for pathogenesis and virus transmission pathways Characterization of severe acute respiratory syndrome-associated coronavirus (SARS CoV) spike glycoprotein-mediated viral entry Severe acute respiratory syndrome associated coronavirus (SARS CoV) infection inhibition using spike protein heptad repeat-derived peptides Neutralizing antibodies in patients with severe acute respiratory syndrome-associated coronavirus infection Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAB to S1 protein that blocks receptor association

abstract:
  Severe acute respiratory syndrome (SARS) was caused by a previously unrecognized animal coronavirus that exploited opportunities provided by 'wet markets' in southern China to adapt to become a virus readily transmissible between humans. Hospitals and international travel proved to be 'amplifiers' that permitted a local outbreak to achieve global dimensions. In this review we will discuss the substantial scientific progress that has been made towards understanding the virus—SARS coronavirus (SARS-CoV)—and the disease. We will also highlight the progress that has been made towards developing vaccines and therapies The concerted and coordinated response that contained SARS is a triumph for global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.


id: cord-261633-r4qlbnc5
title: Defensins and Sepsis
author: Xie, Guo-Hao
date: 2014-08-19
txt: ./txt/cord-261633-r4qlbnc5.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/25210703/
doi: 10.1155/2014/180109
summary:
  The impact of -defensin-2 on the inflammatory response (e.g., the level of ICAM-1 expression), the severity of lung injury, and the sepsis outcome (7-day survival rate) were observed and evaluated. Previous studies showed that single nucleotide polymorphism (SNP) of -defensin-1 gene (DEFB1) correlates with chronic obstructive pulmonary disease, asthma, genetic allergy, HIV infection, and pseudomonas species infection in oral mucosa [38] [39] [40] [41] [42] . Distribution of alleles, gene types, and haplotypes associating with these loci were studied and compared between septic patients and controls, as well as between survivals and victims of severe sepsis. The authors found that patients with high copy number of DEFA1/DEFA3 were predisposed to severe sepsis and tended to have lower level of plasma HNP1-3 as well as cytokines such as TNF-, IL-6, and IL-10.

abstract:
  Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1β production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.


id: cord-263031-cco2vh0f
author: Vultaggio, Alessandra
date: 2020-06-05
txt: ./txt/cord-263031-cco2vh0f.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/32500526/
doi: 10.1111/all.14407
summary:
  We discuss immunological and clinical considerations for patients on biologic agents (biologicals)targeting the type 2 inflammatory response due to difficult-to-treat allergic diseases in the context of COVID-19. In other coronavirus infections such as severe acute respiratory syndrome (SARS), type I IFN are critical for the initiation of immune response and virus clearance. In line with a paucity of mechanistic data on COVID-19 in the context of type 2 inflammation, knowledge on the disease course in patients treated with biologicals targeting type 2 inflammation due to severe asthma or other atopic diseases, such as CSU, AD and CRSwNP, is scarce to absent. In the past years, new biological therapies for severe asthma, atopic dermatitis (AD), chronicrhinosinusitis with nasal polyps (CRSwNP) and chronic spontaneous urticaria (CSU) have been developed targeting different aspects of the type 2 immune response.

title:
  Considerations on Biologicals for Patients with allergic disease in times of the COVID‐19 pandemic: an EAACI Statement

abstract:
  The outbreak of the SARS‐CoV‐2‐induced Coronavirus Disease 2019 (COVID‐19) pandemic re‐shaped doctor‐patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant numberof the patients are on treatment with biologicals and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS‐CoV‐2 is not known. Severe COVID‐19 patients may experience a “cytokine storm” and associated organ damage characterized by an exaggerated release of proinflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti‐inflammatory cytokines and type 2 responses. This expert based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID‐19 with studies focusing on severe allergic phenotypes lacking. At present, non‐infected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self‐application. In case of an active SARS‐CoV‐2 infection, biological treatment needs to be stopped until clinical recovery and SARS‐CoV‐2 negativity is established and treatment with biologicals should be re‐initiated. Maintenance of add‐on therapy and a constant assessment of disease control, apart from acute management is demanded.


id: cord-270533-s2d3q4ob
title: SARS: future research and vaccine
author: Lau, Yu-Lung
date: 2004-11-05
txt: ./txt/cord-270533-s2d3q4ob.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15531254/
doi: 10.1016/j.prrv.2004.07.005
summary:
  Severe acute respiratory syndrome (SARS), a newly emerged infectious disease of humans in the 21st century, appeared in Guangdong Province in Southern China in November 2002 and spread to 26 countries on five continents along international air travel routes, causing large scale outbreaks in Hong Kong, Singapore and Toronto in early 2003. This novel CoV has satisfied Koch''s postulates for causation by its consistent isolation from SARS patients, viral isolation, reproduction of disease in non-human primates after inoculation and the presence of specific antibody response against the virus in both patients and experimentally infected primates 8 . Indeed, sporadic reemergence of cases have been reported in Guangdong Province as well as from research laboratories Summary Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine.

abstract:
  Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. A novel coronavirus (CoV) was identified as its aetiological agent and its genome was sequenced within months of the World Health Organisation issuing a global threat on SARS. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. This will depend on understanding the pathogenesis and immune response to SARS CoV. Further understanding of the ecology of SARS CoV in human and animals will help prevent future cross species transmission. Likewise for the super-spreading events, clarification of the underlying reasons will be important to prevent a large scale outbreak of SARS. Lastly it is of utmost importance that international research collaboration should be strengthened to deal with SARS and any other emerging infectious disease that can seriously threaten our future.


id: cord-274802-7ioiwsd8
author: Varghese, Praveen Mathews
date: 2020-08-19
txt: ./txt/cord-274802-7ioiwsd8.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33130519/
doi: 10.1016/j.imbio.2020.152008
summary:
  Proteomic and transcriptomic studies on bronchoalveolar lavage (BAL) samples from COVID-19 patients have also revealed considerable insights into the expression of SARS-CoV-2 receptors, co-receptors, immune responses, as well as risk factors for severe disease e.g. age and co-morbidities. Furthermore, treatment with a recombinant C5a antibody on 2 male COVID-19 patients aged 54 and 67 years showed significant benefit in suppressing complement hyperactivation, which contributes to the excessive immune response causing aggravated inflammatory lung injury, a hallmark of SARS-CoV-2 pathogenesis and lethality (242) . Consistent with endothelial injury, the significantly elevated levels of von Willebrand factor found in the patient with severe COVID-19 has led to the idea that the infection of the ACE2 expressing endothelium by SARS-CoV-2 induces injury and activates the complement , which sets up a feedback loop that maintains a state of inflammation (243, (268) (269) (270) . Initial clinical studies in China involving 100 SARS-CoV-2 infected patients, who were treated with Chloroquine, showed amelioration of pneumonia, shortened disease progression, increased resolution of lung lesions on CT, and a better virus-negative conversion (313, 314) .

title:
  Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies

abstract:
  Abstract The current coronavirus pandemic, COVID-19, is the third outbreak of disease caused by the coronavirus family, after Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. It is an acute infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 Virus (SARS-CoV-2). The severe disease is characterised by acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and multiple organ dysfunction syndromes. Currently, no drugs or vaccine exist against the disease and the only course of treatment is symptom management involving mechanical ventilation, immune suppressants, and repurposed drugs. As such the severe form of the disease has a relatively high mortality rate. Last 6 months have seen an explosion of information related to the host receptors, virus transmission, virus structure-function relationships, pathophysiology, co-morbidities, immune response, treatment and most promising vaccines. This review takes a critically comprehensive look at various aspects of host-pathogen interaction in COVID-19. We examine genomic aspects of SARS-CoV-2, modulation of innate and adaptive immunity, complement-triggered microangiopathy, and host transmission modalities. We also examine its pathophysiological impact during pregnancy, in addition to various gaps in our knowledge. The lessons learnt from various clinical trials involving repurposed drugs have been summarised. We also highlight the rationale and likely success of the most promising vaccine candidates.


id: cord-275154-vwnpred5
title: Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza
author: Bermejo-Martin, Jesus F
date: 2009-12-11
txt: ./txt/cord-275154-vwnpred5.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20003352/
doi: 10.1186/cc8208
summary:
  Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. To determine if host immune responses play a potential role in the evolution of mild or severe nvH1N1 illness we performed an analysis of systemic chemokine and cytokine levels in serum from severe and mild nvH1N1 patients shortly following the onset of symptoms.

abstract:
  INTRODUCTION: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.


id: cord-275506-3t5gf66c
title: Hematolological Manifestations of COVID‐19: From Cytopenia to Coagulopathy
author: Agbuduwe, Charles
date: 2020-07-14
txt: ./txt/cord-275506-3t5gf66c.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32663356/
doi: 10.1111/ejh.13491
summary:
  [45] A retrospective study of COVID-19 patients admitted to ICU identified DVT in 25% with advanced age, lower lymphocyte counts and elevated D-dimers being significant risk factors. [63] Currently, the evidence base for the clinical management of COVID-19 is mostly limited to case series and other relatively small observational studies of hospitalised patients. Similar to findings in SARS patients, [64] lymphopenia is the most commonly reported hematological abnormality in COVID-19 and recent data shows that it can be predictive of disease severity. The use of convalescent plasma may, in addition, provide neutralising antibodies against SARS-CoV-2 and a small-scale clinical trial has reported modest but encouraging results in severely-ill but not in critical COVID-19 patients. In view of the increased thrombotic risk associated with COVID-19, prophylactic anticoagulation with low Accepted Article molecular weight heparin is recommended for all hospitalised patients with the disease and clinical trials are needed to investigate the role of more intensive anticoagulation and other experimental therapies.

abstract:
  s Emerging data from the management of patients with Coronavirus Disease 2019 (COVID‐19) suggests multisystemic involvement, including the hemopoietic system. The hematological manifestations of COVID‐19 include blood count anomalies notably lymphopenia and neutrophilia which are of prognostic significance. Hyperferritinemia and elevated lactate dehydrogenase have also been associated with increased mortality. Furthermore, there is considerable evidence of a distinct coagulopathy associated with COVID‐19 characterised by elevated D‐dimers and an increased risk of thrombotic events. This comprehensive review summarises the latest evidence from published studies and discusses the implications of the various hematological manifestations of COVID‐19 with a view to guiding clinical management and risk stratification in this rapidly evolving pandemic.


id: cord-277217-jh4qmoso
author: Ortiz, Justin R.
date: 2013-08-27
txt: ./txt/cord-277217-jh4qmoso.txt
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mime: text/plain
url: http://europepmc.org/articles/pmc5909399?pdf=render
doi: 10.1111/irv.12086
summary:
  35 The study, which analyzes only early childhood disease, reports that 99% of influenza-related cases of severe ALRI among children younger than 5 years occur in low-and middle-income countries, and that 13% of all ALRI in this age group are associated with influenza virus infection. The vast majority of severe illness occurs in low-and middle-income countries, 42 yet there are currently little clinical data or evidence-based management guidelines to improve hospital care for patients in these settings. 66, 67 Hospital care is often delivered by nurses and non-specialist doctors who may have limited time, resources, training, and access to information to manage severely ill patients, 67,68 particularly during a public health emergency like the 2009 influenza pandemic. Several recent global initiatives have developed guidelines for the syndromic management of severe influenza and other severe illness in resource-limited settings.

title:
  Clinical care for severe influenza and other severe illness in resource‐limited settings: the need for evidence and guidelines

abstract:
  The 2009 influenza A (H1N1) pandemic highlighted the importance of quality hospital care of the severely ill, yet there is evidence that the impact of the 2009 pandemic was highest in low‐ and middle‐income countries with fewer resources. Recent data indicate that death and suffering from seasonal influenza and severe illness in general are increased in resource‐limited settings. However, there are limited clinical data and guidelines for the management of influenza and other severe illness in these settings. Life‐saving supportive care through syndromic case management is used successfully in high‐resource intensive care units and in global programs such as the Integrated Management of Childhood Illness (IMCI). While there are a variety of challenges to the management of the severely ill in resource‐limited settings, several new international initiatives have begun to develop syndromic management strategies for these environments, including the World Health Organization's Integrated Management of Adult and Adolescent Illness Program. These standardized clinical guidelines emphasize syndromic case management and do not require high‐resource intensive care units. These efforts must be enhanced by quality clinical research to provide missing evidence and to refine recommendations, which must be carefully integrated into existing healthcare systems. Realizing a sustainable, global impact on death and suffering due to severe influenza and other severe illness necessitates an ongoing and concerted international effort to iteratively generate, implement, and evaluate best‐practice management guidelines for use in resource‐limited settings.


id: cord-277347-5innqoip
author: Huang, Y.
date: 2020-04-24
txt: ./txt/cord-277347-5innqoip.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.04.18.20070656
doi: 10.1101/2020.04.18.20070656
summary:
  title: A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19 METHODS: In this retrospective study, the clinical characteristics, laboratory findings, treatment and outcome data were collected and analyzed from 223 COVID-19 patients stratified into 125 non-severe patients and 98 severe patients. For the diagnosis markers, we found that the levels of D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in severe group compared with the non-severe group on admission (D-Dimer: 87.3% vs. The laboratory findings on admission were shown in Table 1 Table 2 is the summary of case studies (4, 5, 9, 10) examining the association between clinical characters and COVID-19 in the meta-analysis, dividing into two subtypes: severe and non-severe patients. Figure shows the association between elevated risk factors and severity of COVID-19 in the meta-analysis: CRP (A), LDH (B), PCT(C) and D-dimer (D).

title:
  A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19

abstract:
  BACKGROUND: Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. The clinical symptoms of severe and non-severe patients vary, and the case-fatality rate (CFR) in severe COVID-19 patients is very high. However, the information on the risk factors associated with the severity of COVID-19 and of their prognostic potential is limited. METHODS: In this retrospective study, the clinical characteristics, laboratory findings, treatment and outcome data were collected and analyzed from 223 COVID-19 patients stratified into 125 non-severe patients and 98 severe patients. In addition, a pooled large-scale meta-analysis of 1646 cases was performed. RESULTS: We found that the age, gender and comorbidities are the common risk factors associated with the severity of COVID-19. For the diagnosis markers, we found that the levels of D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in severe group compared with the non-severe group on admission (D-Dimer: 87.3% vs. 35.3%, P<0.001; CRP, 65.1% vs. 13.5%, P<0.001; LDH: 83.9% vs. 22.2%, P<0.001; PCT: 35.1% vs. 2.2%, P<0.001), while the levels of aspartate aminotransferase (ASP) and creatinine kinase (CK) were only mildly increased. We also made a large scale meta-analysis of 1646 cases combined with 4 related literatures, and further confirmed the relationship between the COVID-19 severity and these risk factors. Moreover, we tracked dynamic changes during the process of COVID-19, and found CRP, D-dimer, LDH, PCT kept in high levels in severe patient. Among all these markers, D-dimer increased remarkably in severe patients and mostly related with the case-fatality rate (CFR). We found adjuvant antithrombotic treatment in some severe patients achieved good therapeutic effect in the cohort. CONCLUSIONS: The diagnosis markers CRP, D-dimer, LDH and PCT are associated with severity of COVID-19. Among these markers, D-dimer is sensitive for both severity and CFR of COVID-19. Treatment with heparin or other anticoagulants may be beneficial for COVID-19 patients.


id: cord-278013-0d6o5w8z
title: Ascertainment rate of novel coronavirus disease (COVID-19) in Japan
author: Omori, Ryosuke
date: 2020-03-10
txt: ./txt/cord-278013-0d6o5w8z.txt
cache: ./cache/cord-278013-0d6o5w8z.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.03.09.20033183
doi: 10.1101/2020.03.09.20033183
summary:
  We analyzed the epidemiological dataset of confirmed cases with COVID-19 in Japan as of 28 February 2020 and estimated the number of severe and non-severe cases, accounting for under-ascertainment. The ascertainment rate of non-severe cases was estimated at 0.44 (95% confidence interval: 0.37, 0.50), indicating that unbiased number of non-cases would be more than twice the reported count. Considering that reported cases are usually dominated by non-severe 11 cases, the adjusted total number of cases is also about a double of observed count. Here f a denotes the ratio of non-severe to 1 severe reported case of age group a, as estimated from age-specific severity and 2 incidence rate ratio in China (Guan et al., 2020 , Novel, 2020 . The ascertainment rate of non-severe cases, k, was estimated at 0.44 (95% 10 confidence interval (CI): 0.37, 0.50). The present study estimated the ascertainment-adjusted number of cases in 19 Japan, using age-specific severe fraction of cases.

abstract:
  We analyzed the epidemiological dataset of confirmed cases with COVID-19 in Japan as of 28 February 2020 and estimated the number of severe and non-severe cases, accounting for under-ascertainment. The ascertainment rate of non-severe cases was estimated at 0.44 (95% confidence interval: 0.37, 0.50), indicating that unbiased number of non-cases would be more than twice the reported count. Severe cases are twice more likely diagnosed and reported than other cases.


id: cord-278477-9a7gmzz3
author: Huh, Kyungmin
date: 2020-10-21
txt: ./txt/cord-278477-9a7gmzz3.txt
cache: ./cache/cord-278477-9a7gmzz3.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168822720307725?v=s5
doi: 10.1016/j.diabres.2020.108515
summary:
  Aims This study aimed to assess whether body mass index (BMI), fasting plasma glucose (FPG) levels, blood pressure (BP), and kidney function were associated with the risk of severe disease or death in patients with COVID-19. To examine the association between baseline health status and the risk of severe disease in patients with COVID-19, we performed a case-control study, using data from the nationwide registry of COVID-19 cases and from the biennial health checkup database in South Korea. In the present study based on a nationwide COVID-19 registry combined with an independent regular health checkup data, the effect of FPG levels and eGFR on the risk of severe or fatal COVID-19 varied between sex and age groups. In our retrospective study using a nationwide health checkup database, high FPG levels and low eGFR were significantly associated with the risk of severe COVID-19 (including fatal illness among women.

title:
  Impact of obesity, fasting plasma glucose level, blood pressure, and renal function on the severity of COVID-19: a matter of sexual dimorphism?

abstract:
  Aims This study aimed to assess whether body mass index (BMI), fasting plasma glucose (FPG) levels, blood pressure (BP), and kidney function were associated with the risk of severe disease or death in patients with COVID-19. Methods Data on candidate risk factors were extracted from patients’ last checkup records. Propensity score-matched cohorts were constructed, and logistic regression models were used to adjust for age, sex, and comorbidities. The primary outcome was death or severe COVID-19, defined as requiring supplementary oxygen or higher ventilatory support. Results Among 7,649 patients with confirmed COVID-19, 2,231 (29.2%) received checkups and Severe COVID-19 occurred in 307 patients (13.8%). A BMI of 25.0–29.9 was associated with the outcome among women (aOR, 2.29; 95% CI,: 1.41–3.73) and patients aged 50–69 years (aOR, 1.64; 95% CI, 1.06–2.54). An FPG ≥126 mg/dL was associated with poor outcomes in women (aOR, 2.06; 95% CI, 1.13–3.77) but not in men. Similarly, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was a risk factor in women (aOR, 3.46; 95% CI, 1.71–7.01) and patients aged <70 years. Conclusions The effects of BMI, FPG, and eGFR on outcomes associated with COVID-19 were prominent in women but not in men.


id: cord-285557-my16g91c
title: Severe acute respiratory syndrome (SARS)—paradigm of an emerging viral infection
author: Berger, A.
date: 2004-01-31
txt: ./txt/cord-285557-my16g91c.txt
cache: ./cache/cord-285557-my16g91c.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/14675864/
doi: 10.1016/j.jcv.2003.09.011
summary:
  This strengthened the case for the novel coronavirus being the cause of SARS, but only after it had been shown to cause a similar illness in artificially infected macaques could it be regarded as fulfilling all four of Koch''s postulates ; World Health Organisation Multicentre Collaborative Networks for Severe Acute Respiratory Syndrome Diagnosis, 2003) . Nevertheless, and despite considerable progress in this field, much remains to be done until laboratory tests become a useful tool for the management of SARS cases (World Health Organization Multicentre Collaborative Network for Severe Acute Respiratory Syndrome Diagnosis, 2003) . An enzyme-linked immunosorbent assay (ELISA) was developed that detects antibodies in the serum of SARS patients and reliably yields positive results at around day 21 after the onset of illness (World Health Organization Multicentre Collaborative Network for Severe Acute Respiratory Syndrome Diagnosis, 2003).

abstract:
  Abstract An acute and often severe respiratory illness emerged in southern China in late 2002 and rapidly spread to different areas of the Far East as well as several countries around the globe. When the outbreak of this apparently novel infectious disease termed severe acute respiratory syndrome (SARS) came to an end in July 2003, it had caused over 8000 probable cases worldwide and more than 700 deaths. Starting in March 2003, the World Health Organization (WHO) organised an unprecedented international effort by leading laboratories working together to find the causative agent. Little more than one week later, three research groups from this WHO-coordinated network simultaneously found evidence of a hitherto unknown coronavirus in SARS patients, using different approaches. After Koch’s postulates had been fulfilled, WHO officially declared on 16 April 2003 that this virus never before seen in humans is the cause of SARS. Ever since, progress around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the first isolate being obtained, its complete genome was sequenced. Diagnostic tests based on the detection of SARS-CoV RNA were developed and made available freely and widely; nevertheless the SARS case definition still remains based on clinical and epidemiological criteria. The agent’s environmental stability, methods suitable for inactivation and disinfection, and potential antiviral compounds have been studied, and development of vaccines and immunotherapeutics is ongoing. Despite its grave consequences in humanitarian, political and economic terms, SARS may serve as an example of how much can be achieved through a well-coordinated international approach, combining the latest technological advances of molecular virology with more “traditional” techniques carried out to an excellent standard.


id: cord-286683-mettlmhz
author: Ortiz-Prado, Esteban
date: 2020-05-30
txt: ./txt/cord-286683-mettlmhz.txt
cache: ./cache/cord-286683-mettlmhz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.diagmicrobio.2020.115094
doi: 10.1016/j.diagmicrobio.2020.115094
summary:
  Interestingly, the increased amounts of proinflammatory cytokines in serum associated with pulmonary inflammation and extensive lung damage described both in SARS [59] and MERS diseases [60] were also reported in the early study of 41 patients with COVID-19 in Wuhan [41] . A recently published case report of a patient with mild-to-moderate COVID-19 revealed the presence of an increased activated CD4+ T cells and CD8+ T cells, antibody-secreting cells (ASCs), follicular helper T cells (TFH cells), and anti-SARS-CoV-2 IgM and IgG antibodies, suggesting that both cellular and humoral responses are important in containing the virus and inhibiting severe pathology [82] . Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series

title:
  Clinical, molecular and epidemiological characterization of the SARS-CoV2 virus and the Coronavirus disease 2019 (COVID-19), a comprehensive literature review

abstract:
  Abstract Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms. Those that infect animals can evolve and become infectious to humans. Three recent examples of these viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19). COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 20th May 2020 show more than 5 million people had been infected with the virus, causing more than 330,000 deaths in over 210 countries worldwide. The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).


id: cord-286799-q9p5kg65
author: Huang, Huang
date: 2020-10-05
txt: ./txt/cord-286799-q9p5kg65.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/33123541/
doi: 10.3389/fmed.2020.557453
summary:
  The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups but that only comorbidity with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10 mg/L), and lactate dehydrogenase (LDH >250 U/L) were independently associated with the later disease development. Finally, we evaluated their prognostic values with receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, though a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC = 0.944, sensitivity = 0.941, and specificity = 0.902). Finally, we evaluated their prognostic values with receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, though a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC = 0.944, sensitivity = 0.941, and specificity = 0.902).

title:
  Prognostic Factors for COVID-19 Pneumonia Progression to Severe Symptoms Based on Earlier Clinical Features: A Retrospective Analysis

abstract:
  Approximately 15–20% of COVID-19 patients will develop severe pneumonia, and about 10% of these will die if not properly managed. Earlier discrimination of potentially severe patients basing on routine clinical and laboratory changes and commencement of prophylactical management will not only save lives but also mitigate the otherwise overwhelming healthcare burden. In this retrospective investigation, the clinical and laboratory features were collected from 125 COVID-19 patients who were classified into mild (93 cases) or severe (32 cases) groups according to their clinical outcomes after 3–7 days post-admission. The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups but that only comorbidity with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10 mg/L), and lactate dehydrogenase (LDH >250 U/L) were independently associated with the later disease development. Finally, we evaluated their prognostic values with receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, though a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC = 0.944, sensitivity = 0.941, and specificity = 0.902). A combination consisting of three or four factors could further increase the prognostic value. Additionally, measurable serum viral RNA post-admission independently predicted the severe illness occurrence. In conclusion, a combination of general clinical characteristics and laboratory tests could provide a highly confident prognostic value for identifying potentially severe COVID-19 pneumonia patients.


id: cord-286843-8qh1pblc
title: Impact of microbial Aetiology on mortality in severe community-acquired pneumonia
author: Quah, Jessica
date: 2018-09-04
txt: ./txt/cord-286843-8qh1pblc.txt
cache: ./cache/cord-286843-8qh1pblc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30180811/
doi: 10.1186/s12879-018-3366-4
summary:
  Univariate and multivariate logistic regression showed that serum procalcitonin, APACHE II severity score and mixed viral-bacterial infection were associated with increased risk of hospital mortality. Postulated prohibitive factors against the routine performance of viral diagnostics tests in patients with severe CAP may include a lack of clear clinical guidelines, perceived low cost-effectiveness and the paucity of effective anti-viral therapies for respiratory viruses other than influenza. Our primary hypothesis was that respiratory viruses were important causative pathogens in severe CAP and was associated with increased mortality when present with bacterial pathogens in mixed viral-bacterial co-infections. performed a prospective observational study on physician practices in the use of respiratory virus diagnostics demonstrating that despite clinical guideline recommendations on testing of respiratory viruses during influenza season, less than half of patients admitted to the intensive care unit with pneumonia were tested for viral pathogens [14] .

abstract:
  BACKGROUND: The impact of different classes of microbial pathogens on mortality in severe community-acquired pneumonia is not well elucidated. Previous studies have shown significant variation in the incidence of viral, bacterial and mixed infections, with conflicting risk associations for mortality. We aimed to determine the risk association of microbial aetiologies with hospital mortality in severe CAP, utilising a diagnostic strategy incorporating molecular testing. Our primary hypothesis was that respiratory viruses were important causative pathogens in severe CAP and was associated with increased mortality when present with bacterial pathogens in mixed viral-bacterial co-infections. METHODS: A retrospective cohort study from January 2014 to July 2015 was conducted in a tertiary hospital medical intensive care unit in eastern Singapore, which has a tropical climate. All patients diagnosed with severe community-acquired pneumonia were included. RESULTS: A total of 117 patients were in the study. Microbial pathogens were identified in 84 (71.8%) patients. Mixed viral-bacterial co-infections occurred in 18 (15.4%) of patients. Isolated viral infections were present in 32 patients (27.4%); isolated bacterial infections were detected in 34 patients (29.1%). Hospital mortality occurred in 16 (13.7%) patients. The most common bacteria isolated was Streptococcus pneumoniae and the most common virus isolated was Influenza A. Univariate and multivariate logistic regression showed that serum procalcitonin, APACHE II severity score and mixed viral-bacterial infection were associated with increased risk of hospital mortality. Mixed viral-bacterial co-infections were associated with an adjusted odds ratio of 13.99 (95% CI 1.30–151.05, p = 0.03) for hospital mortality. CONCLUSIONS: Respiratory viruses are common organisms isolated in severe community-acquired pneumonia. Mixed viral-bacterial infections may be associated with an increased risk of mortality.


id: cord-287872-i6cahnxd
author: Wendt, F. R.
date: 2020-11-12
txt: ./txt/cord-287872-i6cahnxd.txt
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mime: text/plain
url: http://medrxiv.org/cgi/content/short/2020.11.08.20227884v1?rss=1
doi: 10.1101/2020.11.08.20227884
summary:
  Severe respiratory COVID-19 and hospitalized COVID-19 were genetically correlated with 127 and 174 phenotypes, respectively, after multiple testing correction ( Figure 1A ). With 188 traits genetically correlated with either COVID-19 outcome after multiple testing correction (Table S3) , we tested for causality among UKB, severe respiratory COVID-19, hospitalized COVID-19. After multiple testing correction we detected 24 and 42 latent causal genetic relationships with severe respiratory COVID-19 and hospitalized COVID-19, respectively (Table S4) . After multiple testing correction there were no significant differences between genetic causality proportions estimated for severe respiratory COVID-19 and hospitalized COVID-19. Phenome-wide assessment of 14 COVID-19 liability loci (across three severity outcomes: severe respiratory, hospitalized COVID-19, and all COVID-19) identified 439 significant (FDR q<0.05, Figure 1C ) out of 7,221 phenotypes across six ancestries (Table S5) .

title:
  Host genetic liability for severe COVID-19 overlaps with alcohol drinking behavior and diabetic outcomes and in over 1 million participants

abstract:
  To distinguish correlation from causation, we performed in-silico analyses of three COVID-19 outcomes (N>1,000,000). We show genetic correlation and putative causality with depressive symptoms, metformin use, and alcohol use. COVID-19 risk loci associated with several hematologic biomarkers. Comprehensive findings inform genetic contributions to COVID-19 epidemiology, molecular mechanisms, and risk factors.


id: cord-294700-pb5k21da
author: Dulek, Daniel E
date: 2020-08-18
txt: ./txt/cord-294700-pb5k21da.txt
cache: ./cache/cord-294700-pb5k21da.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32808988/
doi: 10.1093/jpids/piaa098
summary:
  Although the majority of SARS-CoV-2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials. Given the lack of available results from randomized-controlled trials of immunomodulatory therapy in children with COVID-19, the risk-benefit ratio for most pediatric patients points toward supportive care as the key management strategy. In the absence of such opportunity, and recognizing that definitive evidence is lacking, consideration for use of immunomodulatory agents in cases of SARS-CoV-2 infection with clinical and biochemical evidence of cytokine storm physiology (e.g., features of secondary HLH) should be limited to patients with clear evidence of critical COVID-19 disease and risk for multi-organ failure.

title:
  Multidisciplinary Guidance Regarding the Use of Immunomodulatory Therapies for Acute COVID-19 in Pediatric Patients

abstract:
  BACKGROUND: Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of SARS-CoV-2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C). METHODS: A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion. RESULTS: The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multi-organ involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized. CONCLUSIONS: Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.


id: cord-296605-p67twx7a
title: Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS)
author: LAU, Arthur Chun-Wing
date: 2004-03-10
txt: ./txt/cord-296605-p67twx7a.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15912185/
doi: nan
summary:
  title: Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS) Most SARS patients would require high flow oxygen supplementation, 20–30% required intensive care unit (ICU) or high dependency care, and 13–26% developed acute respiratory distress syndrome (ARDS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). More than onethird of all the SARS patients required high flow oxygen therapy [4] , 20-30% required intensive care unit (ICU) admission or high dependency care, and 13-26% developed acute respiratory distress syndrome (ARDS) [5, 6] . Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China Evaluation of non-invasive positive pressure ventilation in treatment for patients with severe acute respiratory syndrome Clinical observation of non-invasive positive pressure ventilation (NIPPV) in the treatment of severe acute respiratory syndrome (SARS)

abstract:
  Severe acute respiratory syndrome (SARS) is frequently complicated with acute respiratory failure. In this article, we aim to focus on the management of the subgroup of SARS patients who are critically ill. Most SARS patients would require high flow oxygen supplementation, 20–30% required intensive care unit (ICU) or high dependency care, and 13–26% developed acute respiratory distress syndrome (ARDS). In some of these patients, the clinical course can progress relentlessly to septic shock and/or multiple organ dysfunction syndrome (MODS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). Superimposed bacterial and other opportunistic infections are common, especially in those treated with mechanical ventilation. Subcutaneous emphysema, pneumothoraces and pneumomediastinum may arise spontaneously or as a result of positive ventilatory assistance. Older age is a consistently a poor prognostic factor. Appropriate use of personal protection equipment and adherence to infection control measures is mandatory for effective infection control. Much of the knowledge about the clinical aspects of SARS is based on retrospective observational data and randomized-controlled trials are required for confirmation. Physicians and scientists all over the world should collaborate to study this condition which may potentially threaten human existence.


id: cord-297323-l3f12hg4
author: Amor, Sandra
date: 2020-09-26
txt: ./txt/cord-297323-l3f12hg4.txt
cache: ./cache/cord-297323-l3f12hg4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/cei.13523
doi: 10.1111/cei.13523
summary:
  Like many viruses, SARS‐CoV‐2 has evolved strategies to circumvent innate immune detection including low CpG levels in the genome, glycosylation to shield essential elements including the receptor binding domain, RNA shielding and generation of viral proteins that actively impede anti‐viral interferon responses. These subsequently induce expression of type I IFNs (IFNα/β) and interferon stimulated genes (ISGs) [figure 2] many of which have potent antiviral activities, as well as other proinflammatory mediators e.g. cytokines, chemokines and antimicrobial peptides that are essential to initiate the host innate and adaptive immune response. Likewise, viral load, obesity, gender, race, blood groups and comorbidities have all been reported to influence the response to SARS-CoV-2 infection, [ Table 4 ; (101) (102) (103) (104) (105) (106) (107) (108) (109) (110) (111) (112) ] although few studies have fully examined the extent to which subversion and activation of innate immune components contribute to susceptibility in these cases. Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection

title:
  Innate immunity during SARS‐CoV‐2: evasion strategies and activation trigger hypoxia and vascular damage

abstract:
  Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses, SARS‐CoV‐2 has evolved strategies to circumvent innate immune detection including low CpG levels in the genome, glycosylation to shield essential elements including the receptor binding domain, RNA shielding and generation of viral proteins that actively impede anti‐viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion, SARS‐CoV‐2 infection activates innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines, and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin‐angiotensin system due to downregulation of angiotensin converting enzyme 2, the receptor for SARS‐CoV‐2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS‐CoV‐2 infection, much of which is based on the knowledge from SARS‐CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID‐19 may help explain factors that contribute to the variety of clinical manifestations and outcome of SARS‐CoV‐2 infection.


id: cord-299093-zp07aqpm
title: Mechanisms of SARS-CoV-2 transmission and pathogenesis
author: Harrison, Andrew G.
date: 2020-10-14
txt: ./txt/cord-299093-zp07aqpm.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33132005/
doi: 10.1016/j.it.2020.10.004
summary:
  Thus, evasion of IFN signaling by SARS-CoV-2 and impaired IFN production in J o u r n a l P r e -p r o o f human peripheral blood immune cells might contribute to the productive viral replication, transmission, and severe pathogenesis during COVID-19, although further testing is warranted to fully dissect these putative evasion pathways [95] . For instance, Krt18-hACE2 and betaactin-hACE2-transgenic mice rapidly succumb to SARS-CoV-2 infection with lung infiltration of inflammatory immune cells inducing severe pulmonary disease, accompanied by evident thrombosis and anosmia, which partially recapitulate human COVID-19 [114] [115] . Furthermore, upon viral challenge, lymphocytes have expanded in rhesus macaque models around 5 dpi with complementary B-cell responses against SARS-CoV-2 Spike appearing 10-15 dpi in blood samples [125] ; expansion of these adaptive immune compartments was analogous to those observed in COVID-19 patients [37, 125, [132] [133] [134] .

abstract:
  The emergence of SARS-coronavirus 2 (SARS-CoV-2) marks the third highly pathogenic coronavirus to spill over into the human population. SARS-CoV-2 is highly transmissible with a broad tissue tropism that is likely perpetuating the pandemic. However, important questions remain regarding its transmissibility and pathogenesis. In this review, we summarize current SARS-CoV-2 research, with an emphasis on transmission, tissue tropism, viral pathogenesis, and immune antagonism. We further present advances in animal models that are important for understanding the pathogenesis of SARS-CoV-2, vaccine development, and therapeutic testing. When necessary, comparisons are made from studies with SARS to provide further perspectives on COVID-19, as well as draw inferences for future investigations.


id: cord-299150-1noy0z88
title: Clinical Trial Endpoints in Severe COVID-19
author: Desai, Aakash
date: 2020-06-06
txt: ./txt/cord-299150-1noy0z88.txt
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extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0025619620305413?v=s5
doi: 10.1016/j.mayocp.2020.05.025
abstract: nan
summary:
  However, clinical trials of agents tested for severe COVID19 may not necessarily test for mortality outcomes as the primary endpoint, as was highlighted in the press release of the recent remdesivir trial. Since drugs improving mortality in severe COVID-19 is the most important endpoint to achieve both from clinical and public policy standpoint, we evaluated the type of primary endpoints currently being assessed in randomized controlled trials (RCTs) in severe COVID19. Our analysis found that only 6/19 (30%) ongoing phase III RCT in severe COVID19 have mortality as the standalone primary endpoint or a part of composite endpoint. Given that mortality is as high as 25% in severe COVID19 who need ICU care and average time to death is 3-6 days [2, 3] , the number of mortality events needed and follow-up time do not pose an impediment for analysis of mortality as the primary endpoint.


id: cord-300559-vuuxthx2
author: Deng, Ming
date: 2020-06-29
txt: ./txt/cord-300559-vuuxthx2.txt
cache: ./cache/cord-300559-vuuxthx2.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/oby.22943
doi: 10.1002/oby.22943
summary:
  Logistic regression analysis showed that male, high body mass index (especially obesity), elevated fasting blood glucose and urinary protein positive are all risk factors for severe young COVID‐19 patients. The analysis showed that a high body mass index (especially obesity), an elevated FBG level, an elevated LDH level, and urinary protein positivity were all risk factors for severe COVID-19 in these young patients. A recently published study from China also showed that in metabolic-associated fatty liver disease patients, obesity can increase the risk for severe COVID-19 by about 6-fold [22] . Notably, in the present study, all of the severely or critically ill COVID-19 patients were males, an observation which may also be related to the distribution of obesity in China. Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease

title:
  Obesity as a Potential Predictor of Disease Severity in Young COVID‐19 Patients: A Retrospective Study

abstract:
  OBJECTIVE: To explore the indicators for severity in young COVID‐19 patients age between 18 to 40. METHODS: This retrospective cohort study includes 65 consecutively admitted COVID‐19 patients age between 18 to 40 in Zhongnan Hospital of Wuhan University. Among them, 53 were moderate cases, 12 were severe or critical cases. Epidemiological, clinical and laboratory characteristics and treatment data were collected. A multivariate logistic regression analysis was implemented to explore risk factors. RESULTS: The severe/critical cases have obviously higher BMI (average 29.23 vs. 22.79kg/m(2)) and lower liver CT value (average 50.00 vs. 65.00mU) than moderate cases group. The severe/critical cases have higher fasting glucose, alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , and creatinine (Cr) compared with moderate cases (All P<0.01) . More severe/critical cases (58.33% vs. 1.92%) have positive urine protein. The severe/critical cases will experience a significant process of serum albumin decline. Logistic regression analysis showed that male, high body mass index (especially obesity), elevated fasting blood glucose and urinary protein positive are all risk factors for severe young COVID‐19 patients. CONCLUSION: Obesity is an important predictor of severity in young COVID‐19 patients. The main mechanism is related to the damage of liver and kidney.


id: cord-302115-r39ser2c
author: Matricardi, Paolo Maria
date: 2020-05-02
txt: ./txt/cord-302115-r39ser2c.txt
cache: ./cache/cord-302115-r39ser2c.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/pai.13271
doi: 10.1111/pai.13271
summary:
  We propose here the first model, explaining how the outcome of first, crucial 10‐15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, Mannose Binding Lectin ). The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. All rights reserved We focused on humoral components and, in particular on natural antibodies and MBL, to ascertain whether these players of the innate immunity fit all the epidemiological and clinical pre-conditions presented in the last three months by SARS-CoV-2. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for Accepted Article This article is protected by copyright.

title:
  The first, holistic immunological model of COVID‐19: implications for prevention, diagnosis, and public health measures

abstract:
  The natural history of COVID‐19 caused by SARS‐CoV‐2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi‐organ failure, eventually fatal, mainly in the eldest. We propose here the first model, explaining how the outcome of first, crucial 10‐15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, Mannose Binding Lectin ). If SARS‐CoV‐2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Low‐moderate physical activity can still be recommended. However, extreme physical activity and hyperventilation during the incubation days and early stages of COVID‐19, facilitates early direct penetration of high numbers of virus particles in the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus bypassing the efficient immune barrier of the upper airways mucosa in already infected, young and otherwise healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time‐sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID‐19 at all ages.


id: cord-302166-tah3jdw0
title: Severe COVID-19 in the young and healthy: monogenic inborn errors of immunity?
author: Zhang, Shen-Ying
date: 2020-06-18
txt: ./txt/cord-302166-tah3jdw0.txt
cache: ./cache/cord-302166-tah3jdw0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41577-020-0373-7
doi: 10.1038/s41577-020-0373-7
summary:
  We suggest that these patients may become critically ill because of monogenic inborn errors that disrupt protective immunity to SARS-CoV-2. We suggest that these patients may become critically ill because of monogenic inborn errors that disrupt protective immunity to SARS-CoV-2. Studies since 1996 have identified a number of monogenic inborn errors of immunity (IEIs) underlying life-threatening infectious diseases, including specific viral diseases, in previously healthy patients 1,3-6 . The search for monogenic IEIs conferring predisposition to severe COVID-19 in previously healthy children and young or even middle-aged adults should therefore involve the genome-wide, agnostic testing of genetic hypotheses (see also COVID Human Genetic Effort) 10 . The discovery of monogenic IEIs to SARS-CoV-2 should help unravel the mechanistic basis of the immunopathogenesis of severe COVID-19 in young, previously healthy individuals. A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection

abstract:
  Severe COVID-19 is rare in previously healthy individuals who are less than 50 years of age, affecting probably no more than 1 in 1,000 such infected individuals. We suggest that these patients may become critically ill because of monogenic inborn errors that disrupt protective immunity to SARS-CoV-2.


id: cord-303196-ltmu3ncu
author: Pfitscher, L. C.
date: 2016-05-21
txt: ./txt/cord-303196-ltmu3ncu.txt
cache: ./cache/cord-303196-ltmu3ncu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27207244/
doi: 10.1186/s12879-016-1525-z
summary:
  title: Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study BACKGROUND: The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. In each group, PLTC (less severe cases) and Severe Maternal Outcome (SMO: MNM + MD) cases were compared to evaluate the factors potentially associated with more severe disease, including delay in obstetric care, also using the Prevalence Ratios plus their respective 95 % CI adjusted for the design effect of cluster sampling. Our study presents the burden of severe respiratory diseases among cases of severe maternal morbidity and results of the 2009 H1N1 influenza pandemic, considering 27 referral maternity hospitals in Brazil.

title:
  Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study

abstract:
  BACKGROUND: The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. METHODS: A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. RESULTS: Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. CONCLUSIONS: Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.


id: cord-305223-go75cs6r
title: Clinical Characteristics of Patients with Severe Pneumonia Caused by the SARS-CoV-2 in Wuhan, China
author: Wang, Yafei
date: 2020-08-25
txt: ./txt/cord-305223-go75cs6r.txt
cache: ./cache/cord-305223-go75cs6r.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1159/000507940
doi: 10.1159/000507940
summary:
  title: Clinical Characteristics of Patients with Severe Pneumonia Caused by the SARS-CoV-2 in Wuhan, China OBJECTIVES: The aim of this study was to explore the clinical characteristics and risk factors of severe pneumonia caused by the SARS-CoV-2 in Wuhan, China. SPSS was used for data analysis to explore the clinical characteristics and risk factors of patients with severe pneumonia caused by SARS-CoV-2. Statistical analysis showed that advanced age, increased D-Dimer, and decreased lymphocytes were characteristics of the patients with severe pneumonia. Severe pneumonia usually progresses rapidly, and many clinical indicators can change in a short time, especially lymphocyte count, D-Dimer and serum albumin values, and chest CT manifestations. The result suggests that advanced age, lymphocyte decline, and D-dimer elevation are independent risk factors for patients with severe COVID-19. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

abstract:
  BACKGROUND: A new virus broke out in Wuhan, Hubei, China, that was later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical characteristics of severe pneumonia caused by SARS-CoV-2 are still not clear. OBJECTIVES: The aim of this study was to explore the clinical characteristics and risk factors of severe pneumonia caused by the SARS-CoV-2 in Wuhan, China. METHODS: The study included patients hospitalized at the Central Hospital of Wuhan who were diagnosed with COVID-19. Clinical features, chronic comorbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of patients with severe pneumonia caused by SARS-CoV-2. RESULTS: A total of 110 patients diagnosed with COVID-19 were included in the study, including 38 with severe pneumonia and 72 with nonsevere pneumonia. Statistical analysis showed that advanced age, increased D-Dimer, and decreased lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with severe pneumonia showed that the illness can progress rapidly. CONCLUSIONS: Advanced age, decreased lymphocytes, and D-Dimer elevation are important characteristics of patients with severe COVID-19. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.


id: cord-305583-p2jp5fiq
title: UK malaria treatment guidelines 2016
author: Lalloo, David G.
date: 2016-02-12
txt: ./txt/cord-305583-p2jp5fiq.txt
cache: ./cache/cord-305583-p2jp5fiq.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0163445316000475
doi: 10.1016/j.jinf.2016.02.001
summary:
  Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. There are now three main therapeutic options for the treatment of uncomplicated falciparum malaria in adults in the UK: artemisinin combination therapy (ACT), oral atovaquoneeproguanil or quinine plus doxycycline (or quinine plus clindamycin in certain circumstances) (see Box 4 for details of doses). 52 In line with the WHO guidelines, we recommend that IV artesunate should be used preferentially over quinine as the drug of choice for treatment of severe falciparum malaria in children (grade 1A).

abstract:
  1.Malaria is the tropical disease most commonly imported into the UK, with 1300–1800 cases reported each year, and 2–11 deaths. 2. Approximately three quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other species of plasmodium: Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. 4. Mixed infections with more than one species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. 5. There are no typical clinical features of malaria; even fever is not invariably present. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints. 6. A diagnosis of malaria must always be sought in a feverish or sick child or adult who has visited malaria-endemic areas. Specific country information on malaria can be found at http://travelhealthpro.org.uk/. P. falciparum infection rarely presents more than six months after exposure but presentation of other species can occur more than a year after exposure. 7. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until more than one blood specimen has been examined. Other travel related infections, especially viral haemorrhagic fevers, should also be considered. 8. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites. P. falciparum and P. vivax (depending upon the product) malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens. RDTs for other Plasmodium species are not as reliable. 9. Most patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h as patients can deteriorate suddenly, especially early in the course of treatment. In specialised units seeing large numbers of patients, outpatient treatment may be considered if specific protocols for patient selection and follow up are in place. 10. Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether–lumefantrine (Riamet(®)) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(®)) is an alternative. Quinine or atovaquone–proguanil (Malarone(®)) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe malaria is a rare complication of P. vivax or P. knowlesi infection and also requires parenteral therapy. 12. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1A). Patients treated with intravenous quinine require careful monitoring for hypoglycemia. 13. Patients with severe or complicated malaria should be managed in a high-dependency or intensive care environment. They may require haemodynamic support and management of: acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, seizures, and severe intercurrent infections including Gram-negative bacteraemia/septicaemia. 14. Children with severe malaria should also be treated with empirical broad spectrum antibiotics until bacterial infection can be excluded (Grade 1B). 15. Haemolysis occurs in approximately 10–15% patients following intravenous artesunate treatment. Haemoglobin concentrations should be checked approximately 14 days following treatment in those treated with IV artemisinins (Grade 2C). 16. Falciparum malaria in pregnancy is more likely to be complicated: the placenta contains high levels of parasites, stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. 17. Uncomplicated falciparum malaria in the second and third trimester of pregnancy should be treated with artemether–lumefantrine (Grade 2B). Uncomplicated falciparum malaria in the first trimester of pregnancy should usually be treated with quinine and clindamycin but specialist advice should be sought. Severe malaria in any trimester of pregnancy should be treated as for any other patient with artesunate preferred over quinine (Grade 1C). 18. Children with uncomplicated malaria should be treated with an ACT (artemether–lumefantrine or dihydroartemisinin-piperaquine) as first line treatment (Grade 1A). Quinine with doxycycline or clindamycin, or atovaquone–proguanil at appropriate doses for weight can also be used. Doxycycline should not be given to children under 12 years. 19. Either an oral ACT or chloroquine can be used for the treatment of non-falciparum malaria. An oral ACT is preferred for a mixed infection, if there is uncertainty about the infecting species, or for P. vivax infection from areas where chloroquine resistance is common (Grade 1B). 20. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine (1A). Primaquine is more effective at preventing relapse if taken at the same time as chloroquine (Grade 1C). 21. Primaquine should be avoided or given with caution under expert supervision in patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. 22. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy and when breastfeeding (until the G6PD status of child is known); after initial treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery or cessation of breastfeeding when hypnozoite eradication can be considered. 23. An acute attack of malaria does not confer protection from future attacks: individuals who have had malaria should take effective anti-mosquito precautions and chemoprophylaxis during future visits to endemic areas.


id: cord-308169-a0ft6wdy
title: EAACI position statement on asthma exacerbations and severe asthma
author: Custovic, A.
date: 2013-11-06
txt: ./txt/cord-308169-a0ft6wdy.txt
cache: ./cache/cord-308169-a0ft6wdy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24410781/
doi: 10.1111/all.12275
summary:
  A recently published consensus statement on severe asthma broadened the concept of ''difficult asthma'' to reflect the situation in less developed countries, where access to medications and appropriate care is a major issue, by defining three different patient groups including un(der)treated symptomatic patients, patients with low treatment adherence or unconventional therapies, and those remaining symptomatic despite high doses of anti-asthmatic therapies (13, 14) . Other similar initiatives included the EU-sponsored Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) consortium that has published a consensus-based systematic algorithm approach to differentiate between ''problematic'', ''difficult'' and ''severe refractory'' asthma in the evaluation of patients with chronic severe asthma symptoms for use in clinical research and specialized care (73) . These treatment options for patients with severe asthma who remain symptomatic despite adhering to standard medical care include novel anti-inflammatory drugs that have been shown in preliminary studies to be effective in treating airway inflammation in asthma and so warrant further investigation (32, (83) (84) (85) (86) , and other novel approaches such as bronchial thermoplasty (87) .

abstract:
  Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult‐to‐treat asthma and severe treatment‐resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment‐resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult‐to‐control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult‐to‐control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.


id: cord-312486-rumqopg0
title: On the genetics and immunopathogenesis of COVID-19
author: Jacob, Chaim Oscar
date: 2020-09-10
txt: ./txt/cord-312486-rumqopg0.txt
cache: ./cache/cord-312486-rumqopg0.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1521661620307518
doi: 10.1016/j.clim.2020.108591
summary:
  The question is whether ACE2 expression levels are pertinent to SARS-CoV-2 infection only in the tissues relevant to viral entry and the lungs as its major target, [44, 45] or, given that COVID-19 in its severe form is a systemic disease with multi-organ disfunction [46, 47] , ACE2 expression levels may be important in multiple organs and tissues other than those of the respiratory system. However, the activation of multiple complement pathways, dysregulated neutrophil responses, endothelial injury, and hypercoagulability appear to be interlinked with SARS-CoV-2 infection and instead serve to drive the severity of the disease [91] . Regarding SLE, the prototypic systemic autoimmune disease, a group of investigators suggested that inherent epigenetic dysregulation causing hypomethylation and overexpression of ACE2, the functional receptor for SARS-CoV-2, might facilitate viral J o u r n a l P r e -p r o o f entry, viremia, and increased likelihood of cytokine storm in such patients [153] .

abstract:
  Most severe cases with COVID-19, especially those with pulmonary failure, are not a consequence of viral burden and/or failure of the ‘adaptive’ immune response to subdue the pathogen by utilizing an adequate ‘adaptive’ immune defense. Rather it is a consequence of immunopathology, resulting from imbalanced innate immune response, which may not be linked to pathogen burden at all. In fact, it might be described as an autoinflammatory disease. The Kawasaki-like disease seen in children with SARS-CoV-2 exposure might be another example of similar mechanism.


id: cord-316928-ivwz7jxi
author: Anzola, Gian Paolo
date: 2020-09-23
txt: ./txt/cord-316928-ivwz7jxi.txt
cache: ./cache/cord-316928-ivwz7jxi.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s11739-020-02500-2
doi: 10.1007/s11739-020-02500-2
summary:
  Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome. Partly to help solving this issue, we undertook a prospective study aimed at assessing the clinical characteristics, with particular emphasis on the type of antihypertensive medication, of all consecutive patients presenting at the Emergency Department of a Community Hospital in Gavardo, in the neighborhood of Brescia in Lombardia (Italy), and found to be positive for SARS-CoV-2 infection. In conclusion, we studied prospectively a cohort of consecutive Emergency Department patients found to have COVID-19 and were able to assess the relationship between ACEI and ARB use and the severity of the disease.

title:
  Neither ACEIs nor ARBs are associated with respiratory distress or mortality in COVID-19 results of a prospective study on a hospital-based cohort

abstract:
  Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome. Assess the effect of ACEI/ARBs on outcome in COVID-19 patients. Hospital-based prospective study. A total of 431 patients consecutively presenting at the Emergency Department and found to be affected by COVID-19 were assessed. Relevant clinical and laboratory variables were recorded, focusing on the type of current anti hypertensive treatment. Outcome variables were NO, MILD, SEVERE respiratory distress (RD) operationally defined and DEATH. Hypertension was the single most frequent comorbidity (221/431 = 51%). Distribution of antihypertensive treatment was: ACEIs 77/221 (35%), ARBs 63/221 (28%), OTHER than ACEIs or ARBs 64/221 (29%). In 17/221 (8%) antihypertensive medication was unknown. The proportion of patients taking ACEIs, ARBs or OTHERs who developed MILD or SEVERE RD was 43/77 (56%), 33/53 (52%), 39/64 (61%) and 19/77 (25%), 16/63 (25%) and 16/64 (25%), respectively, with no statistical difference between groups. Despite producing a RR for SEVERE RD of 2.59 (95% CI 1.93–3.49), hypertension was no longer significant in a logistic regression analysis that identified age, CRP and creatinine as the sole independent predictors of SEVERE RD and DEATH. ACEIs and ARBs do not promote a more severe outcome of COVID-19. There is no reason why they should be withheld in affected patients.


id: cord-317058-anvmj4li
author: Liu, Xinkui
date: 2020-06-26
txt: ./txt/cord-317058-anvmj4li.txt
cache: ./cache/cord-317058-anvmj4li.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32589691/
doi: 10.1371/journal.pone.0235459
summary:
  Multivariate logistic analysis indicated that patients aged ≥63 years (odds ratio = 41.0; 95% CI: 2.8, 592.4), with an absolute lymphocyte value of ≤1.02×10(9)/L (odds ratio = 6.1; 95% CI = 1.5, 25.2) and a C-reactive protein level of ≥65.08mg/L (odds ratio = 8.9; 95% CI = 1.0, 74.2) were at a higher risk of severe illness. Our study indicates that age, the absolute lymphocyte count at initial visit, and CRP may be used as predictors during the early stage of diagnosis in patients who are at risk of developing severe COVID-19. Although this study has some limitations, including a small sample size, few variables included in the multivariate analysis, a retrospective cohort design, and limited data collected from medical records, the results of our study indicate that older age, a decreased lymphocyte count on admission, and an increased concentration of serum CRP could serve as early warning signs in patients who are at risk of developing severe COVID-19.

title:
  Analysis of clinical features and early warning signs in patients with severe COVID-19: A retrospective cohort study

abstract:
  Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019. Although previous studies have described the clinical aspects of COVID-19, few studies have focused on the early detection of severe COVID-19. Therefore, this study aimed to identify the predictors of severe COVID-19 and to compare clinical features between patients with severe COVID-19 and those with less severe COVID-19. Patients admitted to designated hospital in the Henan Province of China who were either discharged or died prior to February 15, 2020 were enrolled retrospectively. Additionally, patients who underwent at least one of the following treatments were assigned to the severe group: continuous renal replacement therapy, high-flow oxygen absorption, noninvasive and invasive mechanical ventilation, or extracorporeal membrane oxygenation. The remaining patients were assigned to the non-severe group. Demographic information, initial symptoms, and first visit examination results were collected from the electronic medical records and compared between the groups. Multivariate logistic regression analysis was performed to determine the predictors of severe COVID-19. A receiver operating characteristic curve was used to identify a threshold for each predictor. Altogether,104 patients were enrolled in our study with 30 and 74 patients in the severe and non-severe groups, respectively. Multivariate logistic analysis indicated that patients aged ≥63 years (odds ratio = 41.0; 95% CI: 2.8, 592.4), with an absolute lymphocyte value of ≤1.02×10(9)/L (odds ratio = 6.1; 95% CI = 1.5, 25.2) and a C-reactive protein level of ≥65.08mg/L (odds ratio = 8.9; 95% CI = 1.0, 74.2) were at a higher risk of severe illness. Thus, our results could be helpful in the early detection of patients at risk for severe illness, enabling the implementation of effective interventions and likely lowering the morbidity of COVID-19 patients.


id: cord-318319-efqf5e1i
author: Yamasaki, Yukitaka
date: 2020-07-03
txt: ./txt/cord-318319-efqf5e1i.txt
cache: ./cache/cord-318319-efqf5e1i.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2020.198089
doi: 10.1016/j.virusres.2020.198089
summary:
  The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. Many patients with coronavirus infection disease 2019(COVID-19) are subclinical, and it has been reported that people are J o u r n a l P r e -p r o o f contagious even when asymptomatic [1, 2] , which means preventing the spread of SARS-CoV-2 is challenging [3] . Risk factors of severe pneumonia include age, comorbidities, smoking, reduced lymphocyte count, elevated ferritin levels, and elevated C-reactive protein (CRP) levels [4] [5] [6] [7] [8] [9] . In addition, we examined whether ciclesonide could prevent the development of severe COVID-19 among patients with these predictors. Moreover, the lymphocyte count after ciclesonide therapy in the non-severe pneumonia group was significantly higher (p=0.0156) compared to before treatment (mean 6.14 days, SD 2.17) (Figure 3b ).

title:
  The peripheral lymphocyte count as a predictor of severe COVID-19 and the effect of treatment with ciclesonide

abstract:
  We investigated whether reduced lymphocyte count, could predict the development of severe COVID-19. We also examined whether ciclesonide could prevent the development of severe COVID-19 among patients with the predictors. This was a retrospective cohort study. Of the 30 included patients, 12, 14, and 4 were allocated to severe pneumonia, non-severe pneumonia, and non-pneumonia groups, respectively. The group of the low level of lymphocyte counts of the sixth day after onset was significantly intubated approximately three days later. The incidence of the severe pneumoniae requiring intubation are significantly lower in the patients treated with ciclesonide than without it (11.18 % vs 83.33%, p = 0.0033). The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. 0156) than before. The lymphocyte count could be used to identify patients that may develop severe COVID-19. Treatment with ciclesonide may prevent the development of severe COVID-19.


id: cord-322229-a7sz6e3c
author: Suryadevara, V.
date: 2020-05-12
txt: ./txt/cord-322229-a7sz6e3c.txt
cache: ./cache/cord-322229-a7sz6e3c.txt
extension: .txt
mime: text/plain
url: http://medrxiv.org/cgi/content/short/2020.05.08.20093708v1?rss=1
doi: 10.1101/2020.05.08.20093708
summary:
  The current study represents the mental health survey conducted on the students of South India after the completion of one month quarantine period of the COVID-19 outbreak. Conclusion: In India during the outbreak of COVID-19, an alarming number of students were found to have an impact on mental health due to the outbreak and were observed to have higher levels of stress, anxiety, and depression. This study represents probably the first mental health survey conducted in the students of South Indiaafter the one month quarantine period of the COVID-19 outbreak. After the country''s outbreak of COVID-19, the government of India declared public health emergency of National concern, 26 % of respondents reported severe to extremely severe depressive symptoms; 31.5 % of respondents reported severe to extremely severe anxiety symptoms,and 19 % reported severe to extremely severe stress levels.

title:
  Mental Health Status among the South Indian Pharmacy Students during Covid-19 Pandemic Quarantine Period: A Cross-Sectional Study

abstract:
  Introduction: The COVID-19 outbreak created a major panic among all the citizens of the country owing to its severity, contagiousness within the community, lack of specific treatment and possibility of re-infection. All these factors along with the uncertain behaviour of the virus lead to state of fear and concern all throught out the nation. The current study represents the mental health survey conducted on the students of South India after the completion of one month quarantine period of the COVID-19 outbreak. Methodology: The present study is a cross-sectional, web-based online survey which consists of 21-item DASS questionnaire. This was used to assess the emotional states of depression, anxiety, and stress. Using Google Forms, the questionnaire was randomly distributed among the pharmacy students of selected colleges. Mean with standard deviation was calculated for continuous variables and the number with percentage was calculated for categorical variables. Results: A total of 500 participants responded to the questionnaire. More than half of the responses were received from females (65%). On assessment it was found that, 26 % of respondents reported severe to extremely severe depressive symptoms; 31.5 % of respondents reported severe to extremely severe anxiety symptoms, and 19 % reported severe to extremely severe stress levels. Conclusion: In India during the outbreak of COVID-19, an alarming number of students were found to have an impact on mental health due to the outbreak and were observed to have higher levels of stress, anxiety, and depression. The study findings shows the need of conducting more such studies and can be used to prepare appropriate psychological interventions to improve mental health among the young public during the pandemic.


id: cord-324840-ug5a9wx6
title: The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock
author: De Pascale, Gennaro
date: 2013-10-02
txt: ./txt/cord-324840-ug5a9wx6.txt
cache: ./cache/cord-324840-ug5a9wx6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1155/2013/625803
doi: 10.1155/2013/625803
summary:
  In a cohort of critically ill pediatric patients, Fidler and coworkers observed that MBL levels less than 1000 ng/mL, consistent with MBL-2 gene exon 1 polymorphisms, significantly increased the risk of developing systemic inflammatory response syndrome (SIRS) and progression to severe sepsis/septic shock [32] . The association between the deficiency of this protein and worse outcome during severe systemic infections (i.e., evolution to refractory septic shock) may be also related to the significant interaction between complement activation, inflammatory cytokines'' "storm", and coagulation cascade. Hence MBL, due to its pivotal role in the crosstalking among complement activation, coagulation, and systemic inflammation, may represent a key point for the understanding of the development of systemic severe infections, as interestingly investigated in animal models and clinical studies involving patients with severe sepsis/septic shock.

abstract:
  Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.


id: cord-325170-50oy9qqy
title: Predicting COVID-19 malignant progression with AI techniques
author: Bai, Xiang
date: 2020-03-23
txt: ./txt/cord-325170-50oy9qqy.txt
cache: ./cache/cord-325170-50oy9qqy.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.03.20.20037325
doi: 10.1101/2020.03.20.20037325
summary:
  Specifically, we employed a deep learning-based model to effectively mine the complementary information in static clinical data and serial quantitative chest CT sequence. The differences of clinical and laboratory data and imaging features between the patient with and without severe/critical progression were compared using Chi-square test, Fisher''s exact test, independent t test and paired t test. With the worldwide outbreak of COVID-19, early prediction and early aggressive treatment of mild patients at high risk of malignant progression to severe/critical stage are important ways to reduce mortality. We also demonstrated that our method can effectively fuse these two complementary data and handle time-series information in the quantitative chest CT sequence, which achieved an AUC of 0.954 (95% CI Although lots of clinical, laboratory, and imaging parameters varied significantly between patients with and without severe/critical progression, seven predictive All rights reserved. In conclusion, the deep learning-based method using clinical and quantitative CT data to predict malignant progression to severe/critical stage.

abstract:
  Background: The coronavirus disease 2019 (COVID-19) has become a worldwide pandemic since mid-December 2019, which greatly challenge public medical systems. With limited medical resources, it is a natural strategy, while adopted, to access the severity of patients then determine the treatment priority. However, our work observes the fact that the condition of many mild outpatients quickly worsens in a short time, i.e. deteriorate into severe/critical cases. Hence, it has been crucial to early identify those cases and give timely treatment for optimizing treatment strategy and reducing mortality. This study aims to establish an AI model to predict mild patients with potential malignant progression. Methods: A total of 133 consecutively mild COVID-19 patients at admission who was hospitalized in Wuhan Pulmonary Hospital from January 3 to February 13, 2020, were selected in this retrospective IRB-approved study. All mild patients at admission were categorized into groups with or without malignant progression. The clinical and laboratory data at admission, the first CT, and the follow-up CT at severe/critical stage of the two groups were compared with Chi-square test, Fisher's exact test, and t test. Both traditional logistic regression and deep learning-based methods were used to build the prediction models. The area under ROC curve (AUC) was used to evaluate the models. Results: The deep learning-based method significantly outperformed logistic regression (AUC 0.954 vs. 0.893). The deep learning-based method achieved a prediction AUC of 0.938 by combining the clinical data and the CT data, significantly outperforming its counterpart trained with clinical data only by 0.141. By further considering the temporal information of the CT sequence, our model achieved the best AUC of 0.954. The proposed model can be effectively used for finding out the mild patients who are easy to deteriorate into severe/critical cases, so that such patients get timely treatments while alleviating the limitations of medical resources.


id: cord-328384-jzfr2t3p
title: Predictors of COVID-19 severity: a systematic review and meta-analysis
author: Mudatsir, Mudatsir
date: 2020-09-09
txt: ./txt/cord-328384-jzfr2t3p.txt
cache: ./cache/cord-328384-jzfr2t3p.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.12688/f1000research.26186.1
doi: 10.12688/f1000research.26186.1
summary:
  We performed a systematic review and meta-analysis to assess the risk factors associated with poor clinical outcomes among patients with COVID-19. We performed a systematic review and meta-analysis to evaluate potential risk factors that might influence the severity of COVID-19. Studies were included in this review if they met the following inclusion criteria: (1) assessed the clinical manifestations and laboratory findings of patients with mild to severe COVID-19; The studies included in this systematic review also suggest that the levels of D-dimer were significantly higher in patients with severe COVID-19. Our data suggest that elevated levels of urea and creatinine, and not chronic kidney disease, were associated with severe COVID-19, which indicates that acute inflammation might be caused by SARS-CoV-2 infection. These data suggest that it cannot be determined clearly whether the elevated levels of liver enzymes in patients with severe COVID-19 are caused by direct infection or by drug-induced liver injury.

abstract:
  Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched and extracted as of April 5, 2020. Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin; elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin; and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.


id: cord-331519-ye4dtna5
author: Garibaldi, B. T.
date: 2020-05-26
txt: ./txt/cord-331519-ye4dtna5.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.05.24.20111864
doi: 10.1101/2020.05.24.20111864
summary:
  Conclusions: A combination of demographic and clinical features on admission is strongly associated with progression to severe disease or death in a US cohort of COVID-19 patients. In a sub-group analysis of patients < 60 years of age, we identified male sex (aHR 1.7;95%CI 1.11-2.58), BMI (aHR 1.25 per 5-unit increase; 95%CI 1.14-1.37), CCI (aHR 1.27; 95%CI 1.1-1.46) and respiratory rate (aHR 1.16 per increase of 1 over 18; 95%CI 1.13-1.2) as significantly associated with severe illness or death ( Table 2, Table S5 ). Our study provides valuable insight into the disease trajectories of hospitalized COVID-19 patients in the US and the risk factors associated with severe outcomes. In conclusion, we identified several important demographic and simple to assess factors associated with severe COVID-19 outcomes including age, nursing home status, BMI, D-dimer, troponin, ALC and respiratory rate.

title:
  Patient trajectories and risk factors for severe outcomes among persons hospitalized for COVID-19 in the Maryland/DC region

abstract:
  Background: Risk factors for poor outcomes from COVID-19 are emerging among US cohorts, but patient trajectories during hospitalization ranging from mild-moderate, severe, and death and the factors associated with these outcomes have been underexplored. Methods: We performed a cohort analysis of consecutive COVID-19 hospital admissions at 5 Johns Hopkins hospitals in the Baltimore/DC area between March 4 and April 24, 2020. Disease severity and outcomes were classified using the WHO COVID-19 disease severity ordinal scale. Cox proportional-hazards regressions were performed to assess relationships between demographics, clinical features and progression to severe disease or death. Results: 832 COVID-19 patients were hospitalized; 633 (76.1%) were discharged, 113 (13.6%) died, and 85 (10.2%) remained hospitalized. Among those discharged, 518 (82%) had mild/moderate and 116 (18%) had severe illness. Mortality was statistically significantly associated with increasing age per 10 years (adjusted hazard ratio (aHR) 1.54; 95%CI 1.28-1.84), nursing home residence (aHR 2.13, 95%CI 1.41-3.23), Charlson comorbidity index (1.13; 95% CI 1.02-1.26), respiratory rate (aHR 1.13; 95%CI 1.09-1.17), D-dimer greater than 1mg/dL (aHR 2.79; 95% 1.53-5.09), and detectable troponin (aHR 2.79; 95%CI 1.53-5.09). In patients under 60, only male sex (aHR 1.7;95%CI 1.11-2.58), increasing body mass index (BMI) (aHR1.25 1.14-1.37), Charlson score (aHR 1.27; 1.1-1.46) and respiratory rate (aHR 1.16; 95%CI 1.13-1.2) were associated with severe illness or death. Conclusions: A combination of demographic and clinical features on admission is strongly associated with progression to severe disease or death in a US cohort of COVID-19 patients. Younger patients have distinct risk factors for poor outcomes.


id: cord-332298-ig1j5z07
title: Equine Asthma: Current Understanding and Future Directions
author: Couetil, Laurent
date: 2020-07-30
txt: ./txt/cord-332298-ig1j5z07.txt
cache: ./cache/cord-332298-ig1j5z07.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32903600/
doi: 10.3389/fvets.2020.00450
summary:
  In the last few years, the terminology has further evolved with the term equine asthma (EA) now being recommended to describe horses with chronic respiratory signs ranging in severity from mild to severe that were previously referred as inflammatory airway disease and recurrent airway obstruction, respectively (3) . The future development of new portable and sensitive devices for measuring the lung function of horses (forced oscillation or flow interruption techniques), or the discovery of blood biomarkers for EA would help not only to facilitate the diagnosis of mild and moderate forms of EA in clinical practice, but also to possibly identify new phenotypes for these conditions. Qualitative data were gathered through semi-structured focus group discussions designed to capture current practices and opinions relating to the diagnosis and treatment of lower airway inflammation, as well as familiarity with and views on the most recent ACVIM consensus statement (3), in which the term "mild-moderate equine asthma" was recommended.

abstract:
  The 2019 Havemeyer Workshop brought together researchers and clinicians to discuss the latest information on Equine Asthma and provide future research directions. Current clinical and molecular asthma phenotypes and endotypes in humans were discussed and compared to asthma phenotypes in horses. The role of infectious and non-infectious causes of equine asthma, genetic factors and proposed disease pathophysiology were reviewed. Diagnostic limitations were evident by the limited number of tests and biomarkers available to field practitioners. The participants emphasized the need for more accessible, standardized diagnostics that would help identify specific phenotypes and endotypes in order to create more targeted treatments or management strategies. One important outcome of the workshop was the creation of the Equine Asthma Group that will facilitate communication between veterinary practice and research communities through published and easily accessible guidelines and foster research collaboration.


id: cord-332480-3uodkrkp
title: Adjunct immunotherapies for the management of severely ill COVID-19 patients
author: Bonam, Srinivasa Reddy
date: 2020-04-30
txt: ./txt/cord-332480-3uodkrkp.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32562483/
doi: 10.1016/j.xcrm.2020.100016
summary:
  Current COVID-19 data clearly highlight that cytokine storm and activated immune cell migration to the lungs characterize the early immune response to COVID-19 that causes severe lung damage and development of acute respiratory distress syndrome. 13, 14, 16, 17 Of note, similar to severely ill COVID-19 cases, elevated serum levels of IL-6, TNF-α and IFN-γ have been consistently observed in cytokine release syndrome (CRS) that is common in the patients receiving T cell-engaging immunotherapies (bispecific antibody constructs or chimeric antigen receptor (CAR) T cell therapies). A randomized Phase 1b/2, double-blind, placebo-controlled clinical trial is currently recruiting patients to investigate the therapeutic efficacy of a humanized anti-GM-CSF IgG1 monoclonal antibody TJ003234 in severely ill COVID-19 patients (NCT04341116). 68 Similarly, treatment of ten severely ill COVID-19 patients with 200 mL of convalescent plasma containing viral neutralizing antibody titers more than 1:640 (A dilution of plasma that neutralized 100 TCID 50 (50% tissue-culture-infective dose) of SARS-CoV-2) led to reduced CRP levels, undetectable viremia and improved clinical symptoms.

abstract:
  Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has infected millions with more than 181,000 fatal cases as of 22nd April 2020. Currently, there are no specific COVID-19 therapies. Most patients depend on mechanical ventilation. Current COVID-19 data clearly highlight that cytokine storm and activated immune cell migration to the lungs characterize the early immune response to COVID-19 that causes severe lung damage and development of acute respiratory distress syndrome. In view of uncertainty associated with immunosuppressive treatments such as corticosteroids and their possible secondary effects, including risks of secondary infections, we suggest immunotherapies as an adjunct therapy in severe COVID-19 cases. Such immunotherapies based on inflammatory cytokine neutralization, immunomodulation and passive viral neutralization, not only reduce inflammation, inflammation-associated lung damage, or viral load, but could also prevent intensive care unit hospitalization and dependency on mechanical ventilation both of which are limited resources.


id: cord-334564-bqh9jkds
title: Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health
author: Raony, Ícaro
date: 2020-05-27
txt: ./txt/cord-334564-bqh9jkds.txt
cache: ./cache/cord-334564-bqh9jkds.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.01170
doi: 10.3389/fimmu.2020.01170
summary:
  Since COVID-19 is associated with increased levels of pro-inflammatory cytokines (8) , an immune signature shared with several psychiatric disorders, we propose how the relationship between SARS-CoV-2/host can possibly impair interactions between the immune, nervous and endocrine systems, leading to psychiatric symptoms. Several studies have demonstrated psychiatric manifestations in patients with MERS or SARS during the acute phase, such as increased stress levels, impaired memory, symptoms of depression, anxiety, PTSD, psychoses, and suicidal behavior (28) (29) (30) (31) (32) (33) . If the increase in cytokine levels and the manifestation of psychiatric symptoms are related to the severity of the symptoms of SARS-CoV infection, the "cytokine storm" might also be related to the "mental health thunderstorms" seen in patients with COVID-19? Similar to possible mechanisms involved in the impacts of SARS-CoV-2 infection on mental health, social isolation may also be associated with dysfunctional psycho-neuroendocrine-immune interactions, which in turn can contribute to the development or the worsening of psychiatric disturbances (Figure 2) .

abstract:
  Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation. Herein we discuss the growing evidence suggesting that the relationship between SARS-CoV-2 and host may also trigger changes in brain and behavior. Based on the similarity of SARS-CoV-2 with other coronaviruses, it is conceivable that changes in endocrine and immune response in the periphery or in the central nervous system may be involved in the association between SARS-CoV-2 infection and impaired mental health. This is likely to be further enhanced, since millions of people worldwide are isolated in quarantine to minimize the transmission of SARS-CoV-2 and social isolation can also lead to neuroendocrine-immune changes. Accordingly, we highlight here the hypothesis that neuroendocrine-immune interactions may be involved in negative impacts of SARS-CoV-2 infection and social isolation on psychiatric issues.


id: cord-334735-up81jotp
title: Das schwere akute Atemwegssyndrom (SARS)
author: Gillissen, Adrian
date: 2003
txt: ./txt/cord-334735-up81jotp.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/12811416/
doi: 10.1007/s00063-003-1271-z
summary:
  Severe acute respiratory syndrome (SARS) is a viral disease, observed primarily in Southern China in November 2002, with variable flu-like symptoms and pneumonia, in approx. Weitere Fälle wurden aus Vietnam, Singapur und den USA (hier mation about a new syndrome by the end of February 2003, after the first cases outside the Republic of China had been observed. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong Identification of a novel coronavirus in patients with severe acute respiratory syndrome Guideline on management of severe acute respiratory syndrome (SARS) A novel coronavirus associated with severe acute respiratory syndrome SARS: imaging of severe acute respiratory syndrome Coronavirus as possible cause of severe acute respiratory syndrome A cluster of cases of severe acute respiratory syndrome in Hong Kong Severe acute respiratory syndrome (SARS): infection control Dieses Prinzip ist bei den Neuraminidaseinhibitoren zur Therapie der Influenza bekannt und klinisch umgesetzt [7, 9, 21] .

abstract:
  Severe acute respiratory syndrome (SARS) is a viral disease, observed primarily in Southern China in November 2002, with variable flu-like symptoms and pneumonia, in approx. 5% leading to death from respiratory distress syndrome (RDS). The disease was spread over more than 30 states all over the globe by SARS-virus-infected travelers. WHO and CDC received first information about a new syndrome by the end of February 2003, after the first cases outside the Republic of China had been observed. A case in Hanoi, Vietnam, led to the first precise information about the new disease entity to WHO, by Dr. Carlo Urbani, a co-worker of WHO/Doctors without Borders, who had been called by local colleagues to assist in the management of a patient with an unknown severe disease by the end of February 2003. Dr. Urbani died from SARS, as did many other health care workers. In the meantime, more than 7,000 cases have been observed worldwide, predominantly in China and Hong Kong, but also in Taiwan, Canada, Singapore, and the USA, and many other countries, and more than 600 of these patients died from RDS. Since the beginning of March 2003, when WHO and CDC started their activities, in close collaboration with a group of international experts, including the Bernhard-Nocht-Institute in Hamburg and the Department of Virology in Frankfurt/Main, a previously impossible success in the disclosure of the disease was achieved. Within only 8 weeks of research it was possible to describe the infectious agent, a genetically modified coronavirus, including the genetic sequence, to establish specific diagnostic PCR methods and to find possible mechanisms for promising therapeutic approaches. In addition, intensifying classical quarantine and hospital hygiene measures, it was possible to limit SARS in many countries to sporadic cases, and to reduce the disease in countries such as Canada and Vietnam. This review article summarizes important information about many issues of SARS (May 15th, 2003).


id: cord-335061-wn8u7u9y
title: A Learning-based Model to Evaluate Hospitalization Priority in COVID-19 Pandemics
author: Zheng, Yichao
date: 2020-08-03
txt: ./txt/cord-335061-wn8u7u9y.txt
cache: ./cache/cord-335061-wn8u7u9y.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S2666389920301203?v=s5
doi: 10.1016/j.patter.2020.100092
summary:
  This model is found effective to identify severe COVID-19 cases on admission, with a sensitivity of 84.6%, a specificity of 84.6%, and an accuracy of 100% to predict the disease progression toward rapid deterioration. In light of this unmet need in efficient triage of COVID-19 cases, the study is sought to 56 develop and validate a learning-based model that evaluates patients'' priority of being 57 admitted to hospital care due to their appearance or susceptibility toward severe 58 COVID-19. As this study was sought to identify 86 the hospitalization priority according to the prehospital assessment of severe COVID-19 87 risk, only clinical data obtained on admission were used to evaluate the importance of 88 clinical variables in identification of severe or potentially severe cases. To assess the 358 effectiveness of models in early prediction of severe progressions, patients who were 359 presented with non-severe symptom on admission but developed severe disease during 360 hospitalization were enrolled as an external testing set for analysis.

abstract:
  Summary The emergence of novel coronavirus disease 2019 (COVID-19) is placing an increasing burden on the healthcare systems. Although the majority of infected patients have non-severe symptoms and can be managed at home, some individuals may develop severe disease and are demanding the hospital admission. Therefore, it becomes paramount to efficiently assess the severity of COVID-19 and identify hospitalization priority with precision. In this respect, a 4-variable assessment model, including lymphocyte, lactate dehydrogenase (LDH), C-reactive protein (CRP) and neutrophil, is established and validated using the XGBoost algorithm. This model is found effective to identify severe COVID-19 cases on admission, with a sensitivity of 84.6%, a specificity of 84.6%, and an accuracy of 100% to predict the disease progression toward rapid deterioration. It also suggests that a computation-derived formula of clinical measures is practically applicable for the healthcare administrators to distribute hospitalization resources to the most needed in epidemics and pandemics.


id: cord-337137-0ey40gzw
title: How the SARS coronavirus causes disease: host or organism?
author: Lo, Anthony WI
date: 2005-12-17
txt: ./txt/cord-337137-0ey40gzw.txt
cache: ./cache/cord-337137-0ey40gzw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16362992/
doi: 10.1002/path.1897
summary:
  Published by John Wiley & Sons, Ltd. Severe acute respiratory syndrome (SARS) is a new viral disease caused by a novel coronavirus, SARS-CoV ( Figure 1 ) [1, 2] . Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in-situ hybridization study of fatal cases Detection of severe acute respiratory syndrome-associated coronavirus in pneumocytes of the lung Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2 The severe acute respiratory syndrome coronavirus 3a protein up-regulates expression of fibrinogen in lung epithelial cells Autoantibodies against human epithelial cells and endothelial cells after severe acute respiratory syndrome (SARS)-associated coronavirus infection

abstract:
  The previous epidemic of severe acute respiratory syndrome (SARS) has ended. However, many questions concerning how the aetiological agent, the novel SARS coronavirus (CoV), causes illness in humans remain unanswered. The pathology of fatal cases of SARS is dominated by diffuse alveolar damage. Specific histological changes are not detected in other organs. These contrast remarkably with the clinical picture, in which there are apparent manifestations in multiple organs. Both pathogen and host factors are important in the pathogenesis of SARS. The choice of specific receptors and the unique genome of the SARS‐CoV are important elements in understanding the biology of the pathogen. For the host cells, the outcome of SARS‐CoV infection, whether there are cytopathic effects or not, depends on the cell types that are infected. At the whole‐body level, immune‐mediated damage, due to activation of cytokines and/or chemokines and, perhaps, autoimmunity, may play key roles in the clinical and pathological features of SARS. Continued research is still required to determine the pathogenetic mechanisms involved and to combat this new emerging human infectious disease. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


id: cord-337599-dyxfsojh
title: Primed for Global Coronavirus Pandemic: Emerging Research and Clinical Outcome
author: Ahamad, Shakir
date: 2020-09-19
txt: ./txt/cord-337599-dyxfsojh.txt
cache: ./cache/cord-337599-dyxfsojh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33070079/
doi: 10.1016/j.ejmech.2020.112862
summary:
  Under such circumstances, drug repurposing has emerged as a realistic and effective strategy to counter the virus menace in the short run, and several antiviral and antimalarial medicines are currently in different stages of clinical trials. Researchers are also experimenting with nutrients, vitamins, monoclonal antibodies, and convalescent plasma as immunity boosters against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This report presents a critical analysis of the global clinical trial landscape for COVID-19 with an emphasis on the therapeutic agents and vaccines currently being tested at pandemic speed. 166 The Institute of Biotechnology, AMMS, China, registered a randomized, double-blind, 167 placebo-controlled Phase-II clinical trial of recombinant novel coronavirus (2019-nCOV) 168 vaccine (adenovirus vector) in healthy adults aged 18 and above on April 10, 2020, (Table1, 169 Entry 6). Clinical study for safety and efficacy of Favipiravir in the treatment of novel 924 coronavirus pneumonia (COVID-19) Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat 1093 Hospitalized Patients with Severe COVID-19 Pneumonia

abstract:
  The global effort to combat and contain the coronavirus disease 2019 (COVID-19) pandemic is now proceeding on a war footing. The world was slow to react to the developing crisis, but once the contours of the impending calamity became evident, the different state and non-state actors have raced to put their act together. The COVID-19 outbreak has blatantly exposed the shortcomings of our healthcare system and the limitations of medical science, despite considerable advances in recent years. To effectively tackle the current epidemic, almost unprecedented in the modern era, there is an urgent need for a concerted, sustained, and coordinated effort towards the development of new diagnostics, therapeutic and vaccines, and the ramping up of the healthcare infrastructure, especially in the poorer, underprivileged nations. Towards this end, researchers around the world are working tirelessly to develop new diagnostics, vaccines, and therapeutics. Efforts to develop a vaccine against COVID-19 are presently underway in several countries around the world, but a new vaccine is expected only by the end of the year-at the earliest. New drug development against COVID-19 and its approval may take even longer. Under such circumstances, drug repurposing has emerged as a realistic and effective strategy to counter the virus menace in the short run, and several antiviral and antimalarial medicines are currently in different stages of clinical trials. Researchers are also experimenting with nutrients, vitamins, monoclonal antibodies, and convalescent plasma as immunity boosters against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This report presents a critical analysis of the global clinical trial landscape for COVID-19 with an emphasis on the therapeutic agents and vaccines currently being tested at pandemic speed.


id: cord-339266-glmshsh6
author: Yin, R.
date: 2020-05-05
txt: ./txt/cord-339266-glmshsh6.txt
cache: ./cache/cord-339266-glmshsh6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.04.29.20085415
doi: 10.1101/2020.04.29.20085415
summary:
  Objectives:To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with co-morbid neurological symptoms. Conclusions:Patients with COVID-19 with co-morbid neurological diseases had an advanced age, a high rate of severe illness, and a high mortality rate. Clinical case studies of COVID-19 showed that elderly patients and patients with co-morbid neurological diseases had a high rate of severe and critical illness and a high rate of mortality. 13, 14 To the best of our knowledge, except for a few case reports, there has been no clinical analysis of patients with neurological diseases and co-morbid COVID-19. In summary, patients with COVID-19 with co-morbid neurological diseases had an advanced age, a high rate of severe illness, and a high mortality rate. Patients with COVID-19 with co-morbid neurological diseases had an advanced age, a high rate of severe illness, and a high mortality rate.

title:
  Clinical characteristics of 106 patients with neurological diseases and co-morbid coronavirus disease 2019: a retrospective study

abstract:
  Objectives:To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with co-morbid neurological symptoms. Design:Retrospective case series. Setting:Huoshenshan Hospital in Wuhan, China. Participants:From 4 February to 14 April 2020, 106 patients with neurological diseases were enrolled from all patients in the hospital with confirmed COVID-19 and divided into a severe group and a nonsevere group according to their COVID-19 diagnosis. Main outcome measures:Clinical characteristics, laboratory results, imaging findings, and treatment methods were all retrieved through an electronic medical records system and recorded in spreadsheets. Results:The mean (standard deviation, SD) age of patients was 72.7 (11.8) years, and 64 patients were male (60.4%). Among patients with co-morbid neurological diseases, 81 had a previous cerebral infarction (76.4%), 20 had dementia (18.9%), 10 had acute cerebral infarction (9.4%), 5 had sequelae of cerebral haemorrhage (4.7%), 4 had intracranial mass lesions (3.8%), 3 had epilepsy (2.8%), 2 had Parkinsons disease (1.9%), and 1 had myelopathy (0.9%). Fever (n = 62, 58.5%) was the most common symptom. The most common neurological symptoms were myalgia (n = 26, 24.5%), followed by extremity paralysis (n = 20, 18.9%), impaired consciousness (n = 17, 16%), and positive focal neurological signs (n = 42, 39.6%). Eight patients (7.5%) died. There were more patients with altered mental status in the severe group than in the non-severe group (6 [10.2%] vs. 0, P = 0.033). The inflammatory response in the severe group was more significant than that in the non-severe group. There were more patients taking anticoagulant drugs (25 [42.4%] vs. 4 [8.5%], P < 0.001) and sedative drugs (22 [37.3%] vs. 9 [19.1%], P = 0.041) in the severe group than in the non-severe group. Amid all 93 patients with cerebrovascular diseases, only 32 (34.4%) were taking aspirin, 13 (14%) taking clopidogrel, and 33 (35.5%) taking statins. Conclusions:Patients with COVID-19 with co-morbid neurological diseases had an advanced age, a high rate of severe illness, and a high mortality rate. Among the neurological symptoms, altered mental status was more common in patients with severe COVID-19 with co-morbid neurological diseases.


id: cord-345371-pjbviagq
author: Lisi, Lucia
date: 2020-07-23
txt: ./txt/cord-345371-pjbviagq.txt
cache: ./cache/cord-345371-pjbviagq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32710969/
doi: 10.1016/j.bcp.2020.114169
summary:
  The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. Here, we review the recently published literature on the pharmacological treatments used so far and/or undergoing evaluation in clinical trials, with focus on the biochemical mechanisms of action of repurposed or investigational drugs, classified as agents directly targeting the virus ( Figure 1 and Table 1 ) and those used to treat the respiratory distress and inflammation associated with the cytokine release syndrome ( Figure 2 and Table 2 ).

title:
  Approaching Coronavirus Disease 2019: mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2

abstract:
  On March 11, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) a global pandemic. As of July 2020, SARS-CoV-2 has infected more than 14 million people and provoked more than 590,000 deaths, worldwide. From the beginning, a variety of pharmacological treatments has been empirically used to cope with the life-threatening complications associated with Corona Virus Disease 2019 (COVID-19). Thus far, only a couple of them and not consistently across reports have been shown to further decrease mortality, respect to what can be achieved with supportive care. In most cases, and due to the urgency imposed by the number and severity of the patients’ clinical conditions, the choice of treatment has been limited to repurposed drugs, approved for other indications, or investigational agents used for other viral infections often rendered available on a compassionate-use basis. The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. In several months, an exceptionally large number of clinical trials have been designed to evaluate the safety and efficacy of anti-COVID-19 therapies in different clinical settings (treatment or pre- and post-exposure prophylaxis) and levels of disease severity, but only few of them have been completed so far. This review focuses on the molecular mechanisms of action that have provided the scientific rationale for the empirical use and evaluation in clinical trials of structurally different and often functionally unrelated drugs during the SARS-CoV-2 pandemic.


id: cord-346539-kxnrf5g5
title: A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2
author: Riggioni, Carmen
date: 2020-06-14
txt: ./txt/cord-346539-kxnrf5g5.txt
cache: ./cache/cord-346539-kxnrf5g5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32535955/
doi: 10.1111/all.14449
summary:
  This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. The first cases of the coronavirus disease 2019 (COVID19) , caused by the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), were reported in China in December 2019 1 and rapidly led to pandemic. 40, 41 A seroconversion study in COVID-19 patients has found and association between disease severity and SARS-CoV-2-specific IgA levels. Mesenchymal stem cell therapy may potentiate the low IFN-I and -III levels and moderate IFN-stimulated gene response reported in SARS-CoV-2-infected ferrets and COVID-19 patients. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial

abstract:
  In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date it has resulted in ~6.5 million confirmed cases and caused almost 400,000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socio‐economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo‐embolic complications and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19‐related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease.


id: cord-347058-kejcwlng
author: Akbari, Hamed
date: 2020-07-29
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url: https://www.sciencedirect.com/science/article/pii/S002432052030919X?v=s5
doi: 10.1016/j.lfs.2020.118167
summary:
  AIMS: This study aimed to make a comparison between the clinical laboratory-related factors, complete blood count (CBC) indices, cytokines, and lymphocyte subsets in order to distinguish severe coronavirus disease 2019 (COVID-19) cases from the non-severe ones. Our meta-analyses with random-effect models showed a significant decrease in lymphocytes, monocyte, CD4+ T cells, CD8+ T cells, CD3 cells, CD19 cells, and natural killer (NK) cells and an increase in the white blood cell (WBC), neutrophils, neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP)/hs-CRP, erythrocyte sedimentation rate (ESR), ferritin, procalcitonin (PCT), and serum amyloid A (SAA), interleukin-2 (IL-2), IL-2R, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) in the severe group compared to the non-severe group. In this new pandemic pneumonia, the levels of CRP and ESR significantly increased in severe cases compared to non-severe COVID-19 patients [31, 45] , which greatly coincides with those found in the present systematic review and meta-analysis.

title:
  The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

abstract:
  AIMS: This study aimed to make a comparison between the clinical laboratory-related factors, complete blood count (CBC) indices, cytokines, and lymphocyte subsets in order to distinguish severe coronavirus disease 2019 (COVID-19) cases from the non-severe ones. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, Scopus, and Web of Science databases until March 31, 2020. Cochrane's Q test and the I(2) statistic were used to determine heterogeneity. We used the random-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs). KEY FINDINGS: Out of a total of 8557 initial records, 44 articles (50 studies) with 7865 patients (ranging from 13 to 1582), were included. Our meta-analyses with random-effect models showed a significant decrease in lymphocytes, monocyte, CD4+ T cells, CD8+ T cells, CD3 cells, CD19 cells, and natural killer (NK) cells and an increase in the white blood cell (WBC), neutrophils, neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP)/hs-CRP, erythrocyte sedimentation rate (ESR), ferritin, procalcitonin (PCT), and serum amyloid A (SAA), interleukin-2 (IL-2), IL-2R, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) in the severe group compared to the non-severe group. However, no significant differences were found in IL-1β, IL-17, and CD4/CD8 T cell ratio between the two groups. SIGNIFICANCE: Decrease in total lymphocytes and lymphocyte subsets as well as the elevation of CRP, ESR, SAA, PCT, ferritin, and cytokines, but not IL-1β and IL-17, were closely associated with COVID-19 severity, implying reliable indicators of severe COVID-19.


id: cord-349558-vof63qat
author: Jain, Vageesh
date: 2020-03-16
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url: https://doi.org/10.1101/2020.03.15.20035360
doi: 10.1101/2020.03.15.20035360
summary:
  Exclusion criteria included: [1] studies of exclusively paediatric or pregnant patients, due to the varying presentation of COVID-19 in these groups, [2] insufficient data on symptoms/comorbidities on admission in either severe or non-severe disease groups (or ICU and non-ICU All rights reserved. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Table 1 shows details of all included studies including reported findings pertaining to symptoms and comorbidities related to disease severity or ICU admission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Tables 3 and 4 show the odds ratios, 95% confidence intervals and p-values for the individual symptoms and comorbidities that were investigated in at least three of the included studies, for both severe disease and ICU admission, respectively.

title:
  Systematic review and meta-analysis of predictive symptoms and comorbidities for severe COVID-19 infection

abstract:
  Background/introduction COVID−19, a novel coronavirus outbreak starting in China, is now a rapidly developing public health emergency of international concern. The clinical spectrum of COVID−19 disease is varied, and identifying factors associated with severe disease has been described as an urgent research priority. It has been noted that elderly patients with pre-existing comorbidities are more vulnerable to more severe disease. However, the specific symptoms and comorbidities that most strongly predict disease severity are unclear. We performed a systematic review and meta-analysis to identify the symptoms and comorbidities predictive of COVID−19 severity. Method This study was prospectively registered on PROSPERO. A literature search was performed in three databases (MEDLINE, EMBASE and Global Health) for studies indexed up to 5th March 2020. Two reviewers independently screened the literature and both also completed data extraction. Quality appraisal of studies was performed using the STROBE checklist. Random effects meta-analysis was performed for selected symptoms and comorbidities to identify those most associated with severe COVID−19 infection or ICU admission. Results Of the 2259 studies identified, 42 were selected after title and abstract analysis, and 7 studies (including 1813 COVID−19 patients) were chosen for inclusion. The ICU group were older (62.4 years) compared to the non-ICU group (46 years), with a significantly higher proportion of males (67.2% vs. 57.1%, p=0.04). Dyspnoea was the only significant symptom predictive for both severe disease (pOR 3.70, 95% CI 1.83 − 7.46) and ICU admission (pOR 6.55, 95% CI 4.28 − 10.0). Notwithstanding the low prevalence of COPD in severe disease and ICU-admitted groups (4.5% and 9.7%, respectively), COPD was the most strongly predictive comorbidity for both severe disease (pOR 6.42, 95% CI 2.44 − 16.9) and ICU admission (pOR 17.8, 95% CI 6.56 − 48.2). Cardiovascular disease and hypertension were also strongly predictive for both severe disease and ICU admission. Those with CVD and hypertension were 4.4 (95% CI 2.64 − 7.47) and 3.7 (95% CI 2.22 − 5.99) times more likely to have an ICU admission respectively, compared to patients without the comorbidity. Conclusions Dyspnoea was the only symptom strongly predictive for both severe disease and ICU admission, and could be useful in guiding clinical management decisions early in the course of illness. When looking at ICU-admitted patients, who represent the more severe end of the spectrum of clinical severity, COPD patients are particularly vulnerable, and those with cardiovascular disease and hypertension are also at a high-risk of severe illness. To aid clinical assessment, risk stratification, efficient resource allocation, and targeted public health interventions, future research must aim to further define those at high-risk of severe illness with COVID−19.


id: cord-350492-1s6wtj25
author: Ruscitti, Piero
date: 2020-05-28
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url: https://www.ncbi.nlm.nih.gov/pubmed/32574264/
doi: 10.3389/fimmu.2020.01130
summary:
  On these bases, we aimed to review the similarities between severe COVID-19 and diseases included in hyperferritinemic syndrome, from a pathogenic, clinical, and therapeutic point of view, thus proposing new insights to improve the management of those patients. In addition, it has been shown that increased amounts of pro-inflammatory cytokines, including IL-1β, IL-6, IL-12, IFN-γ, IP-10, and MCP1, were associated with pulmonary inflammation and extensive lung damage in SARS patients (25) , thus suggesting a further pathogenic loop in inducing the cytokine storm. The final result is the uncontrolled proliferation of activated immune cells, the massive production of pro-inflammatory mediators, and the development of cytokine storm syndrome, either in severe COVID-19 or SJIA. Considering the lack of efficacy of antiviral therapy for severe coronavirus infection, it is reasonable to postulate the clinical usefulness of specific immunomodulatory therapies (Figure 1) , as observed for other diseases included in hyperferritinemic syndrome such as intravenous immunoglobulins (IVIGs) and tocilizumab, the humanized monoclonal antibody against IL-6 receptor (7).

title:
  Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm

abstract:
  The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been declared as a worldwide public health emergency. Interestingly, severe COVID-19 is characterized by fever, hyperferritinemia, and a hyper-inflammatory process with a massive release of pro-inflammatory cytokines, which may be responsible for the high rate of mortality. These findings may advocate for a similarity between severe COVID-19 and some challenging rheumatic diseases, such as adult onset Still's disease, secondary hemophagocytic lymphohistiocytosis, and catastrophic anti-phospholipid syndrome, which have been included in the “hyperferritinemic syndrome” category. Furthermore, as performed in these hyper-inflammatory states, severe COVID-19 may benefit from immunomodulatory therapies.


