Statin Use Is Associated with More Severe COVID-19 Disease in Hospitalized Patients (preprint)

Background: Given the relatively modest benefit of currently available treatments in improving COVID-19 clinical outcomes, there is an urgent need for novel therapeutic strategies, especially in reversing associated lung inflammation. Attention has focused on repurposing existing agents with immune modulatory properties to accelerate their incorporation into clinical practice. Recent evidence has demonstrated that the cholesterol-lowering agents, statins, are associated with reduced mortality in patients with influenza, sepsis, community-acquired pneumonia, and chronic obstructive pulmonary diseases (COPD). We sought to investigate the relationship between statin use and COVID-19 disease severity in hospitalized patients.Methods: A retrospective analysis of COVID-19 patients admitted to the Johns Hopkins Medical Institutions between March 1, 2020 and June 30, 2020 was performed. The outcomes of interest were mortality and severe COVID-19 infection, as defined by prolonged hospital stay (≥ 7 days) and/ or invasive mechanical ventilation. Logistic regression, Cox proportional hazards regression and propensity score matching were used to obtain both univariable and multivariable associations between covariates and outcomes in addition to the average treatment effect of statin use.Results: Of the 4,447 patients who met our inclusion criteria, 594 (13.4%) patients were exposed to statins on admission, of which 340 (57.2%) were male. The mean age was higher in statin users compared to non-users [64.9 ± 13.4 vs. 45.5 ± 16.6 years, p <0.001]. The average treatment effect of statin use on COVID-19-related mortality was RR=1.00 (95% CI: 0.99 – 1.01, p= 0.928), while its effect on severe COVID-19 infection was RR=1.18 (95% CI: 1.11 – 1.27, p <0.001).Conclusion: Statin use was not associated with altered mortality, but with an 18% increased risk of severe COVID-19 infection.Funding Statement: The retrospective cohort study was supported by the National Institute of Allergy and Infectious Diseases (NIAID)/ National Institutes of Health (NIH) grants UH3AI122309 and K24AI143447 to P.C.KDeclaration of Interests: We declare no competing interests. The Johns Hopkins Core for Clinical Research Data Acquisition provided the data for this analysis.Ethics Approval Statement: All procedures were in accordance with the ethical standards of the Johns Hopkins Medical Institutions and the Johns Hopkins COVID-19 and Data Research Evaluation (CADRE) Committee. The Johns Hopkins University School of Medicine IRB reviewed the study protocol and determined that it qualifies as exempt research under the DHHS regulations.

Factors Associated with Disease Severity and Mortality among Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis (preprint)

Background: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Results: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45; 95%CI 1.23,1.71), dyspnea (RR 2.55; 95%CI 1.88,2.46), diabetes (RR 1.59; 95%CI 1.41,1.78), hypertension (RR 1.90; 95%CI 1.69,2.15). Congestive heart failure (OR 4.76; 95%CI 1.34,16.97), hilar lymphadenopathy (OR 8.34; 95%CI 2.57,27.08), bilateral lung involvement (OR 4.86; 95%CI 3.19,7.39) and reticular pattern (OR 5.54; 95%CI 1.24,24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. Conclusion: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

Predictors of Severity and Mortality Among Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis (preprint)

Background: The COVID-19 pandemic has overwhelmed the global health systems, and it is imperative to understand how to effectively triage patients. Deeper understanding of predictors of disease severity and mortality is pivotal to effectively triage patients with COVID-19 to maximize the benefit of scarce intensive care unit resources, while minimizing the potential harm of outpatient management of ill patients. Methods: We performed a systematic review and meta-analysis of observational studies, assessing factors associated with severity and mortality among laboratory confirmed COVID-19 patients. We searched PubMed, Embase and WHO database for articles up to May 8, 2020. Randomized trials were excluded. Odds ratios (with 95% CI) and risk ratios (with 95% CI) were used to determine the association between the various demographic, clinical, laboratory and radiological factors and the development of severe disease or mortality. We performed meta-regression to determine the percentage change in the occurrence of the outcomes. Heterogeneity across studies were assessed using I2 and Tau2 statistics. Findings: Among 15680 articles obtained from the literature search, 109 articles were included in the analysis. Increasing age and male gender were associated with higher mortality rates and severe disease. The risk of mortality was higher in patients presenting with dyspnea (RR 2·55, 95% CI 1·88–2·46) and hemoptysis (RR 1·62, 95%CI 1·25–2·11). Co-morbidities such as diabetes (RR 1·59, 95%CI 1·41–1·78), hypertension (RR 1·90, 95%CI 1·69–2·15), cardiovascular diseases (RR 2·27, 95% CI 1·88–2·79) and chronic obstructive pulmonary disease (RR 2·29, 95% CI 1·90–2·75) were associated with a higher risk of death. In-hospital complications such as acute respiratory distress syndrome (ARDS), sepsis, shock and acute cardiac injury had adverse outcomes, with ARDS having the highest risk ratio (RR 20·19, 95% CI 10·87–37·52). Lung consolidation on computed tomography (CT) had significant association with death (RR 2·07, 95% CI 1·35–3·16). Congestive heart failure (OR 4·76, 95% CI 1·34–16·97) had greater odds of developing severe disease. Among the radiological features, hilar lymphadenopathy (OR 8·34, 95%CI 2·57–27·08), bilateral lung involvement (OR 4·86, 95%CI 3·19–7·39) and reticular pattern (OR 5·54, 95%CI 1·24–24·67) were more frequently seen in patients with severe disease. Patients with leukocytosis, lymphopenia, elevated C-reactive protein and D-dimer levels had higher odds of severe disease and greater risk of mortality. Interpretation: Our study identified several important predictors of disease severity and mortality among patients with COVID-19. Knowledge of these predictors might help in the prioritization and management of these patients. Funding: NoneDeclaration of Interests: The authors declare no competing interests.