Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients

Abstract

Background: Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. The impact of several risk factors on coronavirus mortality has been previously reported in several meta-analyses limited by small sample sizes. In this systematic review, we aimed to summarize available findings on the association between comorbidities, complications, smoking status, obesity, gender, age and D-dimer, and risk of mortality from COVID-19 using a large dataset from a number of studies.

Method: Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till 31 August 2020. We included all human studies regardless of language, publication date or region. Forty-two studies with a total of 423,117 patients met the inclusion criteria. To pool the estimate, a mixed-effect model was used. Moreover, publication bias and sensitivity analysis were evaluated.

Results: The findings of the included studies were consistent in stating the contribution of comorbidities, gender, age, smoking status, obesity, acute kidney injury, and D-dimer as a risk factor to increase the requirement for advanced medical care. The analysis results showed that the pooled prevalence of mortality among hospitalized patients with COVID-19 was 17.62% (95% CI 14.26-21.57%, 42 studies and 423,117 patients). Older age has shown increased risk of mortality due to coronavirus and the pooled odds ratio (pOR) and hazard ratio (pHR) were 2.61 (95% CI 1.75-3.47) and 1.31 (95% CI 1.11-1.51), respectively. A significant association were found between COVID-19 mortality and male (pOR = 1.45; 95% CI 1.41-1.51; pHR = 1.24; 95% CI 1.07-1.41), and current smoker (pOR = 1.42; 95% CI 1.01-1.83). Furthermore, risk of mortality among hospitalized COVID-19 patients is highly influenced by patients with Chronic Obstructive Pulmonary Disease (COPD), Cardiovascular Disease (CVD), diabetes, hypertension, obese, cancer, acute kidney injury and increase D-dimer.

Conclusion: Chronic comorbidities, complications, and demographic variables including acute kidney injury, COPD, diabetes, hypertension, CVD, cancer, increased D-dimer, male gender, older age, current smoker, and obesity are clinical risk factors for a fatal outcome associated with coronavirus. The findings could be used for disease's future research, control and prevention.

Keywords: Comorbidities; Demographic characteristics; Funnel plot; Heterogeneity; Publication bias; Sensitivity analysis.

Fig. 1

Flow chart of the study search and screening process

Fig. 2

Forest plot showing the proportion of COVID-19 mortality

Fig. 3

Forest plot showing the estimate for the effects of age on COVID-19 mortality

Fig. 4

Forest plot showing the estimate for the effects of gender on COVID-19 mortality

Fig. 5

Forest plot showing the estimate for the effects of smoking status and obesity on COVID-19 mortality

Fig. 6

Forest plot showing the estimate for the effects of CVDs and diabetes on COVID-19 mortality

Fig. 7

Forest plot showing the estimate for the effects of hypertension and COPD on COVID-19 mortality

Fig. 8

Forest plot showing the estimate for the effects of cancer and cardiac injury on COVID-19 mortality

Fig. 9

Forest plot showing the estimate for the effects of acute kidney injury, and D-dimer on COVID-19 mortality

Fig. 10

Funnel plot for publication bias of effect of comorbidities, age, smoking status, obesity, acute kidney injury, gender, and D-dimer on fatal outcome of COVID-19