key: cord-0782590-dtbag7nq
authors: Ren, Lingyun; Yao, Dan; Cui, Zuowei; Chen, Shanshan; Yan, Hong
title: Corona Virus Disease 2019 patients with different disease severity or age range: A single-center study of clinical features and prognosis
date: 2020-12-04
journal: Medicine (Baltimore)
DOI: 10.1097/md.0000000000022899
sha: 9d9d5a1102ede4798737a11e5acc344e55c6dde3
doc_id: 782590
cord_uid: dtbag7nq

This study aimed to describe clinical characteristics and prognosis of Corona Virus Disease 2019 (COVID-19) patients, and to compare these features among COVID-19 patients with different disease severity or age range. Totally, 129 COVID-19 patients were retrospectively enrolled, and the information about demographics, comorbidities, medical histories, clinical symptoms, and laboratory findings at the time of hospital admission were collected. Meanwhile, their clinical outcomes were recorded. According to the fourth version of the guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China, patients were divided into subgroups according to disease severity (moderate and severe/critical) or age (<40 years, 40–64 years and ≥65 years). In total patients, the most common clinical symptoms were fever and cough (all incidences over 50%). Other common clinical symptoms included tiredness/anorexia, shortness of breath, dyspnea, aching pain, expectoration, diarrhea, shivering, and nausea/vomiting. The mortality rate was 5.4%, and the median value of hospital stay was 16.0 (11.0–23.0) days. Subgroup analyses disclosed that severe/critical patients exhibited increased neutrophil count, neutrophils, C-reactive protein, calcitonin, alpha-hydroxybutyric dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, and D-dimer levels, and more deaths compared with that in moderate patients. Regarding age, it correlated with more common fever, higher levels of red blood cell, neutrophil count, lymphocyte count, neutrophils, red cell volume distribution width standard deviation-coefficient of variation, calcitonin, alpha-hydroxybutyric dehydrogenase, Creatine Kinase, aspartate aminotransferase, gamma-glutamyl transferase, and D-dimer, raised death rate and prolonged hospital stay. Our findings provide valuable evidence regarding clinical characteristics and prognosis of COVID-19 patients to help with the understanding of the disease and prognosis improvement.

Corona Virus Disease 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has been officially declared by World Health Organization in March 2020 as a global public health emergency. [1] With the major route of respiratory transmission by airborne spittle and contact transmission, COVID-19 spreads very quickly and widely. [2] Up to April 23, 2020, the COVID-19 pandemic has caused 2,471,136 confirmed cases and 169,006 deaths in over 200 countries. [3] In order to control this disease, multiple interventions have been implemented, including improved rates of diagnostic testing, clinical management (such as antiviral therapy, symptomatic therapy, and traditional Chinese medicine therapy), isolation of suspected cases/confirmed cases contacts, and mobility restrictions. [4] However, this pandemic outbreak is still ongoing. Hence, more efforts to prevent and control COVID-19 pneumonia are essential both in China and globally.

Based on the current epidemiological investigation, the incubation period is generally 3-7 days, and the longest incubation period is no more than 14 days. [5] Common symptoms reported in COVID-19 patients are fever, dry cough, and fatigue. For severe COVID-19 patients, they are reported to present with dyspnea and bilateral ground-glass opacities on chest CT, severe acute respiratory distress syndrome, septic shock, metabolic acidosis, and coagulation dysfunction. [5] Accumulated studies illustrate that COVID-19 is featured with human-to-human transmission, and it is caused by SARSCoV-2 infection that is able to result in severe and even fatal acute respiratory distress syndrome. [2, 6, 7] In order to increase the understanding of COVID-19 and help with the improvement of prognosis, we analyzed detailed clinical data from patients with laboratory-confirmed COVID-19 infection in The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology. Herein, this study aimed to describe clinical characteristics and prognosis in COVID-19 patients, and then compare these features among COVID-19 patients with different disease severity or age range.

A total of 129 patients with laboratory-confirmed COVID-19 infection admitted to The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, between January 20, 2020 and February 4, 2020 were retrospectively analyzed in this study. All patients were diagnosed as COVID-19 according to the diagnostic criteria of the guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China (fourth version) (available at: http://www.nhc.gov.cn/). As suggested in the guideline, the suspected case was defined as a patient with any 1 of the following epidemiological histories and any 2 of the following clinical manifestations:

(1) epidemiological histories: (a) a living or travel history to Wuhan or other districts where the virus was continued to spread by local cases, within 14 days before illness onset; (b) direct contacting with patients who had fever or respiratory symptoms from Wuhan or other districts where virus was continued to spread by local cases, within 14 days before illness onset; (c) there was clustering incidence of COVID-19; (d) there was epidemiological association with COVID-19 patients; (2) clinical manifestations: (a) fever; (b) there was imageology character of febrile pneumonia; (c) the total number of white blood cells in the early stage of the illness onset was normal or decreased, or the lymphocyte count was reduced. A suspected case was confirmed as COVID-19 patient if 1 of following conditions occurred: (a) a positive result of real-time reverse transcriptase-polymerase chain reaction assay of throatswab or blood sample; (b) gene sequencing for throat-swab or blood sample indicated that the viral sequences were highly homologous to the novel coronavirus. The study was approved by the Ethics Committee of our hospital, and patients or their families provided informed consents.

According to the fourth version of the guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China, COVID-19 severity was classified as follows:

(1) Moderate type: fever and respiratory symptoms are presented with pneumonia on chest computed tomography. (2) Severe type: one of the following conditions had to be met: (a) respiratory distress, respiratory rate ≥30 per minute; (b) oxygen saturation on quiescent condition 93%; (c) partial pressure of oxygen in arterial blood/fraction of inspired oxygen 300 mm Hg. (3) Critical type: one of the following conditions had to be met:

(a) respiratory failure occurred and mechanical ventilation was required; (b) shock occurred; (c) patients with other organ dysfunction needing intensive care unit monitoring and treatment.

Based on the above clinical classification criteria, 20 patients were classified as moderate type; 6 patients were classified as severe type; 3 patients were classified as critical type.

Medical records of COVID-19 patients were reviewed. The following characteristics at the time of hospital admission were collected, including (1) demographics: age, and gender;

(2) comorbidities: hypertension, diabetes, hyperlipidemia, chronic pneumopathy, cardiovascular disease, renal dysfunction, and fatty liver; (3) medical histories: tumor history, and surgical history; (4) clinical symptoms: fever, cough, expectoration, tiredness/ anorexia, diarrhea, nausea/vomiting, shortness of breath, dyspnea, aching pain, and shivering; (5) laboratory findings: white blood cell, red blood cell (RBC), hemoglobin, platelet, neutrophil count, lymphocyte count, monocytes count, eosinophil, basophil, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular-hemoglobin concentration, red cell volume distribution width-standard deviation, red cell volume distribution width standard deviation-coefficient of variation (RDW-CV), platelet distribution width, mean platelet volume, platelet large cell ratio, plateletcrit, C-reactive protein (CRP), calcitonin, alpha-hydroxybutyric dehydrogenase (a-HBDH), lactate dehydrogenase (LDH), Creatine Kinase (CK), alanine transaminase, aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), urea, creatinine, and D-dimer.

Besides, treatments after admission and outcomes up to March 23, 2020 were also extracted from the medical records. For treatment after admission, all patients were administered with broad-spectrum coronavirus antiviral therapy, anti-infection therapy, and supportive care. Outcomes included duration of hospital stay, discharge from hospital, remained in hospitalization, transferred to other hospital for further treatment, and death.

SPSS software (Version 22.0, IBM) was used for statistical analysis. Continuous variables described as median with interquartile range, and categorical variables were displayed as count and percentages (%). In order to ensure statistical power, severe type patients, and critical type patients were merged into 1 group in analysis. Comparison between moderate patients and Ren et al. Medicine (2020) 

In total patients, the median age was 50.0 (34.5-61.0) years, and there were 45 (34.9%), 66 (51.2%) and 18 (14.0%) patients with age <40 years, 40-64 years and ≥65 years, respectively. There were 62 (48.1%) males and 67 (51.9%) females ( Table 1) . As to comorbidities, 31 (24.0%), 16 (12.4%), 2 (1.6%), 6 (4.7%), 3 (2.3%), 3 (2.3%), and 3 (2.3%) patients were with hypertension, diabetes, hyperlipidemia, chronic pneumopathy, cardiovascular disease, renal dysfunction, and fatty liver, respectively. As for medical history, 12 (9.3%) patients had tumor history and 25 (19.4%) patients had surgical history. According to COVID-19 severity (from the fourth version of the guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China), patients were classified into moderate type and severe/critical type. Compared to moderate patients (44.0 (32.5--55.5) years), the median age was increased in severe/critical patients (59.5 (48.8-64.0) years) (P < .001). Meanwhile, the number of cases with comorbidity of hypertension (P = .007) and renal dysfunction (P = .028) was higher in severe/ critical patients compared to moderate patients. Furthermore, there was no difference in other demographics, comorbidities, and medical histories between moderate patients and severe/critical patients. The detailed information was shown in Table 1 .

In total patients, the most common clinical symptoms were fever . The frequency of tiredness/ anorexia was more common in severe/critical patients compared to moderate patients (P = .003). However, no difference was found in other clinical symptoms between moderate patients and severe/critical patients. The detailed information was shown in Table 2 .

In total patients, the median value of white blood cell, neutrophil count, lymphocyte count, neutrophils lymphocyte was 4.56 Compared to moderate patients, neutrophil count (P = .024), neutrophils (P = .006), CRP (P = .010) calcitonin (P = .028), a-HBDH (P < .001), LDH (P < .001), AST (P < .001), GGT (P = .004), creatinine (P = .028), and D-dimer (P = .004) were elevated, while lymphocyte count (P = .015) and lymphocyte (P = .005) were decreased in severe/critical patients. However, laboratory characteristics were similar between moderate Table 1 Demographics, comorbidities, and medical histories of COVID-19 patients.

Total Table 3 .

In total patients, 7 (5.4%) cases died, meanwhile 95 (73.6%) cases discharged from hospital, 19 (14.7%) cases remained in hospital and 8 (6.2%) cases were transferred to other hospital. The median value of hospital stay was 16.0 (11.0-23.0) days. Compared to moderate patients, more cases died (P = .001) and were transferred to other hospital (P = .005), while less cases discharged from hospital (P < .001) in severe/critical patients. Whereas no difference in hospital stays (P = .1000) or number of cases remained in hospital (P = .095) was observed between moderate patients and severe/critical patients. The detailed information was shown in Table 4 .

Fever occurred more frequently in older patients (P = .065). Whereas no correlation of age with other clinical symptoms was found (all P > .05). The detailed information was shown in Table 5 .

Age positively correlated with RBC (P = .015), neutrophil count (P = .002), lymphocyte count (P < .001), neutrophils (P = .044), RDW-CV (P = .045), calcitonin (P = .011), a-HBDH (P < .001), LDH (P < .001), CK (P = .014), AST (P = .008), GGT (P = .028), and D-dimer (P = .004) levels, while negatively correlated with lymphocyte (P = .042). However, there was no correlation of age with other laboratory findings (all P > .05). The detailed information was shown in Table 6 .

Age was correlated with increased death rate (P < .001), prolonged hospital stay (P = .028), and decreased hospital discharge (P < .001). However, no correlation of age with other clinical outcomes was displayed (all P > .05). The detailed information was shown in Table 7 .

SARS-CoV-2 belongs to a unique clade of the sarbecovirus subgenus of the Orthocoronavirinae subfamily, which has been identified as the pathogen of COVID-19. [8] Its genetic features are obviously different from SARS-CoV and MERS-CoV, while the homology of SARS-CoV-2 with bat-SL-CoVZC45 is more than 85%. [9] Recent evidence displays that SARS-CoV and MERS-CoV originated in bats, and SARS-CoV-2 likely originated in bats as well. [9] Although the pathogenesis of highly pathogenic COVID-19 is still not completely understood, it has been reported to be similar with MERS-CoV and SARS coronavirus infection, with a rapid progression to respiratory failure. [10] [11] [12] It is now clear that COVID-19 spreads via human-to-human transmission, and this epidemic has been gradually growing in recent weeks. Thus, it is urgent to facilitate efforts to prevent and control COVID-19 pneumonia. Here, we provided an initial assessment of epidemiologic characteristics and prognosis in COVID-19 patients. In this study, we reported that the common clinical symptoms were fever and cough, whose incidences were over 50% in COVID-19 patients, among these symptoms, fever was the most common symptom in COVID-19 patients. Our findings were similar in previous studies reported in COVID-19 patients. [5] Also, these symptoms are also similar with these in patients with MERS-CoV and SARS coronavirus infection. [11, 12] In addition, we found that the median value of hospital stay was 16.0 (11.0-23.0) days, and 5.4% patients died. The results were in line with previous studies that mortality rate ranges from 2.0% to 4.4%. [13] To further analyzed and detailed the clinical data in COVID-19 patients, we divided patients into moderate type, severe type, and critical type according to their disease severity. We found that there was no difference in clinical symptoms between moderate patients and severe/critical patient. Whereas it is notable that severe/critical patients showed an increased trend to occur with tiredness/anorexia compared to moderate patients, which might be explained by that as disease severity manifested, the damage in respiratory and digestive system function was exacerbated in COVID patients. In addition, we discovered that systemic organ indexes (such as neutrophil count, neutrophils, lymphocyte count, lymphocyte calcitonin, a-HBDH, LDH, AST, GGT, creatinine, creatinine, and D-dimer) were related to disease severity in COVID-19 patients, which suggested that COVID-19 patients had impaired cardiac, liver, hematological and cellular immune system function. Based on one previous study, levels of T lymphocytes, D-dimer, C-reactive protein, aspartate aminotransferase, myohemoglobin, CD3+, CD4+, and CD8+ correlated with COVID-19 severity. [7] Although the findings regarding systemic organ indexes are different between our study and previous study, our findings also suggest the damage in cardiac, Table 4 Outcomes of COVID-19 patients. [9] For clinical outcomes, severe/critical patients were more frequently to be transferred to other hospital, and eventually dead, which suggested worse prognosis in severe/critical patients. In order to further explore the correlation of age with clinical characteristics, we divided patients into subgroups based on different age range (<40 years, 40-64 years and ≥65 years), and then we compared the clinical characteristic among them. In this study, fever occurred more frequently in older patients. Of note, patients with age ≥65 years might present with moderate to light fever and even without fever. Regarding laboratory findings, we disclosed the positive correlation of age with RBC, neutrophil count, neutrophils, RDW-CV, CRP, calcitonin, a-HBDH, LDH, CK, AST, GGT, and D-dimer in COVID-19 patients, which suggested that the damage of cardiac, liver, hematological and cellular immune system function deteriorated with age in COVID-19 patients. Furthermore, we also explored the association of age with clinical outcomes in COVID-19 patients, and we discovered that age positively correlated with increased death rate and prolonged hospital stay, which indicated that older age might be a critical index contributing to mortality risk, and the reasons might be that:

(1) older patients are related to a higher frequency of comorbidities (including hypertension, diabetes, chronic pneumopathy, and cardiovascular disease), which might indirectly affect the progression of COVID-19 and increase the difficulty in the treatment of COVID-19 patients, thus, older patients might be related to worse prognosis. [14] [15] [16] (2) older patients were featured with less robust immune responses that devoted into worse prognosis and even death [17, 18] ; (3) older patients had increased risk of drug resistance to attenuate the drug efficacy, thereby, leading to poor treatment outcomes and higher mortality risk. [19] This finding was in line with previous study that also reveals obviously lower survival rate in COVID-19 patients over 75 years old compared to the younger patients. [7] There were several limitations. One is that this was an observational study with a small sample size, potential bias, and residual confounding might exist. Another one is that all patients were just from our hospital, hence, further study with more patients from multicenter is needed.

In conclusion, fever, cough, tiredness/anorexia are common clinical symptoms and the mortality rate is 5.4% in COVID-19 patients. Besides, further subgroup analyses discover that severe/ critical patients present with multiple organ dysfunction and immune dysfunction, importantly, older age might be a critical index contributing to worse disease severity and higher mortality risk.

XXXX. 

World Health Organization

Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia

Coronavirus disease 2019 (COVID-19) Situation Report -94

The effect of human mobility and control measures on the COVID-19 epidemic in China

Epidemiology and clinical features of COVID-19: a review of current literature

Cardiac involvement in COVID-19 patients: risk factors, predictors, and complications: a review

COVID-19 with different severity: a multi-center study of clinical features

A novel coronavirus from patients with pneumonia in China

The guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China (Fourth Version)

Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: early experience and forecast during an emergency response

Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study

Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study

Prevalence and severity of corona virus disease 2019 (COVID-19): a systematic review and meta-analysis

Prevalence of comorbidities and its effects in coronavirus disease 2019 patients: a systematic review and metaanalysis

Connecting type 1 and type 2 diabetes through innate immunity

Tuberculosis and diabetes mellitus: convergence of two epidemics

Geospatial mapping of orthopaedic surgeons age 60 and over and confirmed cases of COVID-19

Age as a risk factor

Risk factors for antibiotic resistance in Streptococcus pneumoniae