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.