key: cord-1056052-nbbg511n
authors: Xu, Zihui; Wang, Zhongjing; Wang, Shuo; Ye, Yingchun; Luo, Deng; Wan, Li; Yu, Ailin; Sun, Lifang; Tesfaye, Solomon; Meng, Qingtao; Gao, Ling
title: The impact of type 2 diabetes and its management on the prognosis of patients with severe COVID‐19
date: 2020-07-08
journal: J Diabetes
DOI: 10.1111/1753-0407.13084
sha: bcdca2737912aced382c3d4ca219e6341142ac71
doc_id: 1056052
cord_uid: nbbg511n

BACKGROUND: Although T2DM patients with COVID‐19 develop a more severe condition compared to those without diabetes, the mechanisms for this are unknown. Moreover, the impact of treatment with anti‐hyperglycemic drugs and glucocorticoids is unclear. METHODS: From 1584 COVID‐19 patients, 364 severe/critical COVID‐19 patients with clinical outcome were enrolled for the final analysis and patients without pre‐existing T2DM but elevated glucose levels were excluded. Epidemiological data were obtained and clinical‐status evaluation carried out to assess the impact of T2DM and its management on clinical outcomes. RESULTS: Of 364 enrolled severe COVID‐19 inpatients, 114 (31.3%) cases had a history of T2DM. 27(23.7%) cases died in T2DM patients, who had more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury, compared with non‐DM patients. In severe COVID‐19 patients with T2DM, we demonstrate a higher risk of all‐cause fatality with glucocorticoid treatment (Adjusted HR, 3.61; 95%CI, 1.14‐11.46; P = 0.029), and severe hyperglycemia (FPG ≥11.1 mmol/L) (Adjusted HR, 11.86; 95%CI, 1.21‐116.44; P = 0.034). CONCLUSIONS: T2DM status aggravated the clinical condition of COVID‐19 patients and increased their critical illness risk. Poor fasting blood glucose (≥ 11.1 mmol/L) and glucocorticoid treatment are associated with poor prognosis for T2DM patients with severe COVID‐19. This article is protected by copyright. All rights reserved.

The pandemic of COVID-19 has now infected over 9 million people worldwide. 1 It has had a catastrophic impact on human lives, particularly the elderly and those with comorbidities. 2, 3 People with type 2 diabetes (T2DM) appear to have a higher risk for SARS-CoV-2 infection with a prevalence of 5-20%, 2-7 because they are generally older and often have other comorbidities. Previous studies have also shown that diabetes is a risk factor for severe cases of viral infections, including SARS, MERS, and H1N1. [8] [9] [10] [11] Moreover, most diabetes patients with COVID-19 end up with a severe form of the disease. 3 In a series of 174 inpatients with COVID-19, 24 of whom had diabetes, there was a rapid progression of the chest infection necessitating a chest CT scan test within 24-48h, 12 a worse prognosis and higher risk/percentage to develop composite endpoints, 3 in the diabetes patients. More importantly, diabetes patients appear to have a higher fatality rate. 3, 13 Patients with diabetes may be susceptible to more severe SARS-CoV-2 infection due to immune system dysfunction. 14 Viral infections could also induce a diabetes state, or worsen hyperglycemia in people with diabetes, which may adversely influence prognosis. [15] [16] [17] [18] Moreover, glucocorticoid use may further aggravate the situation. Antihyperglycaemic treatments may be limited because some oral drugs (i.e. metformin) are potentially harmful to COVID-19 patients with hypoxia. In this observational study, we characterized risk factors for severe COVID-19 with and without T2DM, and described the effects of commonly prescribed anti-hyperglycaemic drugs, and glucocorticoid therapy on clinical outcomes in hospitalized T2DM patients with severe COVID-19, which still remain unanswered. [19] [20] [21] [22] Methods

The diagnosis and clinical classification (mild, moderate, severe, and critical) of COVID-19 patients were carried out by two independent doctors based on the Guideline of Novel Coronavirus Pneumonia (7th Edition) issued by the Chinese National Health Commission. 23 Real-time reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 was performed based on the recommendation by the National Institute for Viral Disease Control and Prevention (China) . 24 All enrolled patients were confirmed COVID-19 cases with RT-PCR and admitted to Renmin Hospital of Wuhan University from January 30, 2020, when the first COVID-19 patient was admitted, to April 26, 2020 , when the last COVID-19 patient was discharged. The clinical outcomes (cured or died) and laboratory parameters on admission and endpoint were recorded. This case series study was approved by the institutional ethics board of Renmin Hospital of Wuhan University (NO. WDRY2020-K081). Written, informed consent was waived in light of the urgent need to collect the data for this study.

The Chinese guideline classified the patients into five categories: asymptomatic (positive virology test without symptoms), mild (symptoms), moderate (CT scan test for viral pneumonia), severe (oxygen saturation ≤93% or oxygenation index < 300), critical (require ICU admission or invasive oxygen treatment). 23 We encountered many difficulties in justifying to request some tests during the outbreak of COVID-19. Oral glucose tolerance test (OGTT) to diagnose T2DM and HbA1c were not routinely requested since they were considered low priorities for COVID-19 patients, making the diagnosis of new onset T2DM screening impossible.

We have therefore included patients with known T2DM history for the Diabetes group excluding patients with elevated glucose (Fasting Blood Glucose ≥ 6.1mmol/L or random glucose ≥ 11.1mmol/L) from non-diabetic group to make the analysis more coherent.

Epidemiological, clinical characteristics, laboratory parameters, clinical status and outcomes were obtained from the electronic medical records of Renmin Hospital of Wuhan University. The data were entered and cross-reviewed by at least two independent team members. Information recorded included demographic data, medical history, underlying comorbidities, symptoms, signs, laboratory findings (e.g., random blood glucose on admission, cellular immunity, metabolic enzymes and other biochemical parameters), treatment measures (e.g., oxygen therapy, ventilator use), and drugs (e.g., insulin, anti-hyperglycaemic agents and glucocorticoids use). Fasting plasma glucose (FPG) was measured for all patients during hospitalization.

Comorbidities, including diabetes, cerebral diseases, cardiovascular diseases, chronic renal diseases, digestive diseases, pulmonary diseases and surgical history, were defined as documented history in the admission notes. Cerebral diseases refer to cerebral infarction, epilepsy, Alzheimer's disease, and Parkinson's disease.

Cardiovascular diseases refer to hypertension, coronary heart disease, arrhythmia, cardiomyopathy and heart failure. Chronic renal diseases refer to chronic renal insufficiency, chronic renal failure, chronic nephritis and nephrotic syndrome. Digestive diseases refer to gastritis, gastric and duodenal ulcer, enteritis, cholecystitis and pancreatitis. Pulmonary diseases refer to asthma, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, tuberculosis, pulmonary embolism, and interstitial pneumonia. Surgical history refers to major abdominal, brain surgery and 

Categorical variables were described as frequency and percentages (%), and continuous variables were described with median and interquartile range (IQR) values.

Means for continuous variables were compared using independent group t tests when the data were normally distributed; otherwise, the Mann-Whitney test was used.

Proportions for categorical variables were compared using Fisher's exact test or the χ 2 test. Logistic regression analysis was used to analyze independent risk factors for mortality of COVID-19 patients. The risk for composite endpoints and corresponding hazard ratio (HR) were analyzed using Cox proportional hazard model. The cumulative rates of death were plotted by applying Kaplan-Meier method. All statistical analyses were performed using SPSS 22.0 (IBM Software) and Graphpad Prism 8 (Graphpad), and p <0.05 was considered statistically significant. 

Of the 364 confirmed severe/critical COVID-19 patients, 305 (83.8%) cases were discharged, and 59 (16.2%) died. 66.5% (242) had one or more coexisting co-morbid medical conditions. The five most common coexisting conditions were: cardiovascular diseases (42.3% (n=154)), DM (31.3% (n=114)), surgical history (12.4% (n=45)), pulmonary disease (10.7% (n=39)), and digestive disease (10.2% (n=37)). The patients aged 60-69 years had the highest percentage (31.0%(n=113)) of COVID-19 compared to other age groups. Fatality rate increased with increasing age ( (Table 1) . Days from symptom onset to admission or gender did not differ between T2DM and non-DM patients (Table 1 ).

In multiple logistic regression analysis for fatality cohorts including age, gender, and co-morbidities (diabetes, cerebral diseases, cardiovascular diseases, chronic renal diseases, digestive disease, pulmonary disease, and surgical history), age (OR, 1.04; 95% CI, 1.02 -1.07; P < 0.001), T2DM (OR, 1.81; 95% CI, 1.06 -3.07; P = 0.029), and surgical history (OR, 2.37; 95% CI, 1.20 -4.71; P = 0.014) were found to be risk factors for fatality of severe/critical inpatients with COVID-19.

There were several differences in laboratory findings between T2DM and non-DM patients, including lower levels of serum albumin and estimated glomerular filtration rate (eGFR), as well as higher levels of white blood cells (WBC), C-reactive protein (CRP), IL-6, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), NT-proBNP, creatine kinase isoenzyme-MB (CK-MB), myoglobin, cardiac troponin I (cTnI), and D-dimer in T2DM (P < 0.05 or P < 0.001). The levels of lymphocyte (LYM), alanine aminotransferase (ALT), creatinine (Cr), creatine kinase (CK), lactic acid (LA), and cellular immune (CD3+, CD4+, CD8+, CD19+, and CD16+56 + cell counts, and CD4+/CD8+) did not differ between T2DM and non-DM (Table 1) . Taken together, our results suggest that T2DM patients with COVID-19 had more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury.

On admission, NEWS2 score of T2DM patients was higher than non-DM patients (Median (IQR), 5(4-8) vs. 5(3-6); P = 0.018) ( Figure 2C ). It indicated that T2DM patients were more severely ill than non-DM patients on admission. During hospitalization, their ventilation therapy was defined as five-category ordinal scale of clinical status, the score in T2DM was higher than non-DM (Median (IQR): 3(2-3) vs.

2(2-3); P < 0.001) ( Figure 2D ). More T2DM patients required IMV/ECMO therapy than non-DM patients (15(13.2%) vs. 8(3.2%); P < 0.001). After adjusting for age, gender, comorbidities, and NEWS2 on admission, the survival rate of T2DM (Adjusted HR, 1.77; 95%CI, 1.02 -3.05; P = 0.041) was lower than non-DM patients with COVID-19 ( Figure 2B ).

In this study, 74(64.9%) of T2DM patients and 134(53.6%) of non-DM patients had glucocorticoid (GC) therapy (dose from 20mg/day to 160 mg/day, duration range of 1-28 days). Admission NEWS2 scores didn't differ significantly between GC and no GC treatment in both T2DM and non-DM patients (P > 0.05; Figure 3D ). After adjusting for age, gender, comorbidities, and NEWS2 on admission, the results significantly demonstrated a lower overall survival rate in the patients treated with GC compared with no GC treatment (Adjusted HR, 3.61; 95%CI, 1.14 -11.46; P = 0.029) ( Figure 3A ).

This contrasted with non-DM patients in whom GC treatment was not risk factor for fatality (Adjusted HR, 1.41; 95%CI, 0.67 -2.96; P = 0.362) ( Figure 3B ). The fatality for DM patients treated with GC was 31.1%, which was about 3 times than that with no GC treatment in both T2DM (10.0%, P=0.012) and non-DM patients (10.3%, P<0.001), and about twice than that with GC treatment in non-DM patients (14.9%, P=0.007) ( Figure 3C ). During hospitalization, more patients treated with GC required invasive ventilation than patients without GC treatment both in T2DM and non-DM patients (P < 0.001; Figure 3E ). The level of IL-6, a marker of inflammation, increased significantly after GC treatment in T2DM patients (P = 0.049), but not in non-DM patients (P = 0.36) ( Figure 3F ).

Among the 114 T2DM patients, 83.3% (n=95) with treated with one or more antihyperglycaemic drugs including: basal insulin (24.6%(n=28)), premixed insulin(14.0%(n=16)), Aspart/Lispro/Human insulin (42.1%(n=48)), acarbose (46.5%(n=53)), metformin (26.3%(n=30)), sulfonylureas (14.9%(n=17)), dipeptidyl peptidase-4 inhibitors (DDP4i) (6.1%(n=7)), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) (0.9%(n=1)). All these drugs were prescribed the conventional dosages according to their instructions. 16 .7% (n=19) of T2DM patients didn't use any anti-hyperglycaemic drugs and were on diet treatment alone. The fatality rates of patients treated with basal insulin (14.3%, P = 0.045), premix insulin (6.3%, P = 0.022), metformin (6.7%, P = 0.008), acarbose (7.5%, P = 0.002), sulfonylureas (5.9%, P = 0.02), insulin (including basal insulin, premixed insulin, and Aspart/Lispro/Human insulin) and oral anti-hyperglycemic drugs (OAHs, including acarbose, metformin, sulfonylureas, DDP4i, and SGLT2i, 7.3%, P = 0.003), and OAHs alone (7.4%, P = 0.009) were lower than that of diet alone treated T2DM patients (42.1%)( Table 2) . NEWS2 scores on admission didn't differ among these patients (P > 0.05). Patients treated with DDP4i or OAHs alone had lower ventilation score than that with diet treatment alone (P < 0.05). Premix insulin, acarbose, metformin, DDP4i, insulin and OAHs, and OAHs alone improved fasting blood glucose metabolism (P < 0.05 or P < 0.001) ( Table 2 ).

The average fasting plasma glucose (FPG) was analyzed, and divided into three P=0.225) showed no difference ( Figure 4 ).

Diabetes has been suggested that confers worse prognosis on COVID-19. 3, 13 However, the impact of T2DM and its management, especially fast glucose control on the prognosis of patients with COVID-19 have not been fully evaluated. Until now, no specific treatment has been validated for its effectiveness, and no antiviral agent has been found to provide benefit in reducing mortality of COVID-19 patients, except for oxygen therapy or early hospitalization. 25 In this observational study, we described that SARS-CoV-2 infection in T2DM was associated with more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury. T2DM aggravated the clinical status of COVID-19, increased their critical illness rate and mortality. GC treatment and fasting blood glucose ≥11.1 mmol/L were found risk factors of fatality in these patients.

The prevalence of diabetes or the comorbidities of diabetes in COVID-19 is from 5-20%. [2] [3] [4] [5] [6] [7] During the early outbreak, hospitalized patients consisted of severe cases older patients amongst whom diabetes patients were well represented. However, later on, more mild cases were hospitalized due to expansion of medical services for COVID-19 patients, and the proportion of diabetes patients started to reflect that of the general population. The most recent survey showed that the overall prevalence of diabetes in China is 12.8% with only half (6%) having a history of diabetes (selfreported diabetes). 27 The overall prevalence of diabetes in those aged ≥40 years was 15.6%. 5 Our data shows that the prevalence history of diabetes in patients with severe COVID-19 is 31.3%, strongly suggesting that diabetes is a risk factor for more severe COVID-19.

Our study also shows that a history of T2DM is a risk factor for the progression and prognosis of COVID-19, 12 with a higher risk of severe pneumonia and higher chest CT scores. It also showed that T2DM patients had more severe organ impairments and worse inflammation. Moreover, diabetes patients have worse glycaemic control which requires more anti-hyperglycaemic treatment following COVID-19 or hospitalization.

Wu et al. 28 reported that diabetes was a risk factor of developing ARDS in COVID-19.

All of these indicate that diabetes status is a major risk factor for worse clinical outcomes/fatality in COVID-19 patients. Indeed, based on our analysis of patients' clinical status, the survival curve showed that the prognosis for T2DM patients was worse. NEWS2 analysis on admission demonstrated that patients with a history of T2DM were generally sicker on admission and older which might be the explanation for the lower survival rate. The time of symptom onset to admission showed no difference between T2DM vs. non-DM patients. However, it has been reported that the SARS-CoV-2 infection was more likely to affect older men with diabetes. 6 As is widely reported, age is a strong indicator for COVID-19 prognosis. Further logistic regression analysis showed that T2DM is an independent risk factor for severe status and fatality of COVID-19 patients. Our data also shows that SARS-CoV-2 infection affects men and women equally, and also indicates that gender may not be a risk factor for a poor outcome, in keeping with recent reports from China. 4, 13 Huang et al. 2 reported that SARS-CoV-2 infection in Wuhan caused multiple organ dysfunction and death in severe COVID-19 patients. In our study, laboratory parameters associated with multiple organ function were tested on admission. The results showed abnormal or worse albumin, eGFR, WBC, CRP, IL-6, AST, LDH, NT-proBNP, CK-MB, myoglobin, cTnI, and D-dimer in COVID-19 patients with T2DM.

These data indicate that SARS-CoV-2 infection in T2DM is associated with more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury. Therefore, diabetes patients are more likely to develop multiple organ failures and die as a result. 4 ACE2, the SARS-CoV-2 receptor, is present in endothelial and smooth muscle cells in multiple organs, 29 suggesting that SARS-CoV-2 infection may induce multiple organ injury, possibly via ACE2. It is well recognized that viral infections can worsen blood glucose control. It has also been found that ACE2 protein shows strong immunostaining in islets, suggesting that SARS-CoV-2 may contribute to the development of diabetes or exacerbation of hyperglycaemia by damaging pancreatic islets via ACE2. 30 Moreover, high levels of inflammatory cytokines such as IL-6 and TNF-a in diabetes patients and animal models suggests that diabetes may significantly promote the production of TLR4-induced IL-6 increase. 12,31 IL-6-dominated cytokine storms have been identified as one of the leading causes of death from pneumonia caused by SARS-CoV-2 infection. 32, 33 During the current pandemic of COVID-19, systemic GC was used for their potent antiinflammatory properties. 34 The use of GC requires a knowledge of the related side effects (e.g. avascular necrosis, psychosis, diabetes), their adequate prevention and a prompt treatment if necessary. A randomized, controlled clinical trial in a preprint posted to medRxiv has found that dexamethasone with mechanic ventilation was shown to reduce deaths from severe COVID-19. 35 However, whether GC should be used for the treatment of lung injury related to SARS-CoV-2 infection is still debatable. 36 In the past, steroid administration did not clearly improve the mortality rate of patients affected by SARS-CoV and MERS-CoV. 36 Our study found that a higher risk of all-cause fatality with GC treatment in severe COVID-19 patients with T2DM.

Although GC was more likely to be used in critical cases, our data indicated that GC treatment may be potentially harmful to T2DM patients with critical COVID-19 if not properly used. Firstly, the fatality in DM patients treated with GC was about twice than that in non-DM patients with GC treatment. Secondly, GC treatment was associated with an increased IL-6 levels in T2DM, but not in non-DM patients. It suggested that we need to further define the indications for GC treatment and use it on the right patients.

The anti-hyperglycaemic treatment approach for T2DM patients with COVID-19 is uncertain because some oral drugs have not been recommended. [19] [20] [21] [22] It seems that insulin may be the safest choice during this uncertainty. We analyzed the influences of anti-hyperglycemic drugs on the prognosis of COVID-19 with T2DM. There were three types of insulin with Aspart/Lispro/Human insulin the most widely used, and four types of oral anti-hyperglycemic drugs with acarbose the most commonly used. Of these anti-hyperglycemic drugs, basal insulin, premix insulin, metformin, acarbose, sulfonylureas, insulin and OAHs, and OAHs alone showed lower fatality than diet treatment alone, despite their similar NEWS2 or clinical status on admission/at baseline. It seems to be consistent with their effects on improving fasting blood glucose metabolism. A recent study reported that a "good blood glucose control (3.9-10moml/L)" was associated with less fatality. 37 Our study indicated similarly but more precisely, we recommended to aim fast blood glucose at (3.9-11.0 mmol/L) for better survival.

We have excluded patients with elevated glucose (FPG ≥ 6.1mmol/L or random glucose ≥ 11.1mmol/L) from non-diabetic group in our analysis. However, they showed same results as pre-existing diabetes patients for those with GC treatment or FPG Table) . Moreover, elevated glucose was found in 182 patients (59 without GC treatment), indicating there is undiagnosed diabetes in these patients.

In summary, a history of T2DM aggravated the clinical status of COVID-19 patients, increased their critical illness and mortality rates. SARS-CoV-2 infection in diabetes led to more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury. GC treatment and fasting plasma glucose ≥11.1 mmol/L were found to be risk factors for fatality in diabetes patients with COVID-19. There are some limitations of this study that took place within the context of an emergency outbreak including: lack of a control group-either as a matched control to compare patient groups or randomized control for the assessment of treatments. Besides, our study is based on small numbers of diabetic patients. However, our study provided evidence for informing clinical decisions. p<0.05 is considered as significant and its value is as indicated in the graph. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. Fig. 4 The overall survival rates of average fasting plasma glucose (FPG) p<0.05 is considered as significant and its value is as indicated in the graph.

This article is protected by copyright. All rights reserved.

Accepted Article

World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report-157

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical Characteristics of Coronavirus Disease 2019 in China

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area

Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS

Diabetes and the severity of pandemic influenza A (H1N1) infection

Pathogenesis of Middle East respiratory syndrome coronavirus

Diabetes is a risk factor for the progression and prognosis of COVID-19

Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan

Reduced IL-4 associated antibody responses to vaccine in early pre-diabetes

Diabetes patients with COVID-19 need better blood glucose management in Wuhan

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Activation of ACE2/angiotensin (1-7) attenuates pancreatic beta cell dedifferentiation in a high-fat-diet mouse model

Loss of ACE2 exaggerates high-calorie dietinduced insulin resistance by reduction of GLUT4 in mice

Coronavirus Infections and Type 2 Diabetes-Shared Pathways with Therapeutic Implications

Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19

COVID-19 and diabetes: Knowledge in progress

Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China

National Health Commission of the People's Republic of China. Diagnosis and treatment protocols of pneumonia caused by a novel coronavirus

National Institute for Viral Disease Control and Prevention (China) . Specific primers and probes for detection 2019 novel coronavirus

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19

The National Early Warning Score 2 (NEWS2) in patients with hypercapnic respiratory failure

Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study

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

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

A new coronavirus associated with human respiratory disease in China

Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics

Insights from immuno-oncology: the Society for Immunotherapy of Cancer Statement on access to IL-6-targeting therapies for COVID-19

Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies

On the use of corticosteroids for 2019-nCoV pneumonia

Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report

Clinical management of severe acute respiratory infection when COVID-19 is suspected

Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes

The authors thank all study participants. This article is protected by copyright. All rights reserved.