key: cord-0703476-pdbj9xfz
authors: Abate, Semagn Mekonnen; Checkol, Yigrem Ali; Mantefardo, Bahiru
title: Global prevalence and determinants of mortality among patients with COVID-19: A systematic review and meta-analysis
date: 2021-03-04
journal: Ann Med Surg (Lond)
DOI: 10.1016/j.amsu.2021.102204
sha: 6380b25ca7aa69f8f3476b96ff0acc116be8045e
doc_id: 703476
cord_uid: pdbj9xfz

BACKGROUND: The challenge of COVID-19 is very high globally due to a lack of proven treatment and the complexity of its transmission. The prevalence of in-hospital mortality among patients with COVID-19 was very high which ranged from 1 to 52% of hospital admission. The prevalence of mortality among intensive care patients with COVID-19 was very high which ranged from 6% to 86% of admitted patients. METHODS: A three-stage search strategy was conducted on PubMed/Medline; Science direct Cochrane Library. The Heterogeneity among the included studies was checked with forest plot, χ2 test, I2 test, and the p-values. Publication bias was checked with a funnel plot and the objective diagnostic test was conducted with Egger's correlation, Begg's regression tests. RESULT: The Meta-Analysis revealed that the pooled prevalence of in-hospital mortality in patients with coronavirus disease was 15% (95% CI: 13 to 17). Prevalence of in-hospital mortality in patients with COVID-19 was strongly related to different factors. Patients with Acute respiratory distress syndrome were eight times more likely to die as compared to those who didn't have, RR = 7.99(95% CI: 4.9 to 13). CONCLUSION: The review revealed that more than fifteen percent of patients admitted to the hospital with coronavirus died. This presages the health care stakeholders to manage morbidity and mortality among patients with coronavirus through the mobilization of adequate resources and skilled health care providers. REGISTRATION: This systematic review and meta-analysis was registered in research registry with UIN of reviewregistry1093.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) that cause Coronavirus disease 2019 (COVID-19) mainly affects the respiratory, gastrointestinal, liver, and central nervous system of humans, livestock, Bats, mice, and other wild animal (1) (2) (3) (4) . The infection mainly affects the respiratory system and present with fever, dry cough, and difficulty of breathing, and lately, the patient may die due to pneumonia and acute respiratory distress syndrome (5) (6) (7) (8) (9) (10) (11) (12) .

The SARS-CoV-2 novel coronavirus was identified in Wuhan, Hubei province of China in December 2019 by the Chinese Center for Disease and Prevention from the throat swab of a patient and the virus is named severe acute respiratory distress CoV-2 by WHO which causes Coronaviruses disease 2019 (COVID-19) (13, 14) . The clinical manifestation of the current coronavirus infection is similar to the one that occurred in China in 2002 by the name severe acute respiratory distress syndrome (15) (16) (17) (18) (19) .

Approximately, 5 million confirmed cases and more than 300 thousand deaths were reported by Though the COVID-19 pandemic has emerged in the Western Pacific region, China, Wuhan city, the number of infected cases, and deaths was the lowest as compared to the American and European regions. The number of laboratory-confirmed cases and deaths in the African region was the lowest for the last couple of months but the rate of spreading in this region is increasing at an alarming rate and is expected to be very high in the next couple of months if it continues as this rate(20-22).

The COVID-19 report in Ethiopia was very small which is 2500 confirmed cases and 27 deaths but there were many cases in short periods which is more than150 cases per day. It is estimated that the number even may be very high because the diagnosis is limited only in the capital (23, 24) .

The challenge of COVID-19 is very high globally due to a lack of proven treatment and the complexity of its transmission (13, (25) (26) (27) (28) (29) (30) (31) . However, it will be more catastrophic for low and J o u r n a l P r e -p r o o f 2. Methods

The systematic review and meta-analysis were conducted based on the Preferred Reporting Items for Systematic and Meta-analysis (PRISMA) protocols (47) . This systematic review and meta-analysis was registered in research registry with UIN of reviewregistry1093 and available at: https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/

Eligibility criteria

All observational (case series, cross-sectional, cohort, and case-control) studies reporting the prevalence of mortality and its determinants among hospitalized patients with coronavirus disease (COVID-19) will be incorporated.

All participants with confirmed Coronaviruses admitted to the hospital for any kind of care will be included.

The primary outcomes of interest were the global prevalence of mortality, morbidity, and complications among patients with Coronaviruses worldwide. Prevalence of ICU mortality Lengths of hospital stay and the number of days on a mechanical ventilator were secondary outcomes.

This systematic review incorporated studies conducted worldwide to assess the prevalence of mortality and associated risk factors among hospitalized patients with COVID-19.

The review included all cross-sectional studies and a single cohort conducted among adult patients hospitalized with COVID-19 to assess mortality in patients with coronavirus infection.

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Studies that didn't report the prevalence of mortality among hospitalized patients with COVID-19, articles that didn't report full information for data extraction, articles with different outcomes of interest, studies with a methodological score less than fifty percent, studies with randomized controlled trials, case reports, and reviews were excluded.

The (coronavirus) or (coronavirus disease 2019)) or (SARS-CoV-2)) or (COVID-19)) and (mortality)) or (fatality)) or (morbidity)) or (comorbidity)) or (complications)) and (risk factors)) or (determinants)) and (prevalence)) and (global). The final search results were shown with the Prisma flow diagram (Fig 1) .

The data from each study were extracted with two independent authors with a customized format excel sheet. The disagreements between the two independent authors were resolved by the other two authors. The extracted data included: Author names, country, date of publication, sample size, events mortality, need of mechanical ventilator, the number of days on a mechanical ventilator, presence of co-morbidities, and complication. Finally, the data were then imported for analysis in R software version 3.6.1 and STATA 14.

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Articles identified for retrieval were assessed by two independent Authors for methodological quality before inclusion in the review using a standardized critical appraisal Tool adapted from the Joanna Briggs Institute(48) (supplemental Table1) and a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions(AMSTAR2) (49) . The disagreements between the Authors appraising the articles were resolved through discussion with the other two Authors. Articles with average scores greater than fifty percent were included for data extraction.

Data analysis was carried out in R statistical software version 3. J o u r n a l P r e -p r o o f 3. Results

A total of 515 articles were identified from different databases and 50 articles were selected for evaluation after the successive screening. Thirty-two Articles with 23082 participants were included and the rest were excluded with reasons (Fig 1) . 

Thirty-two Articles with 23082 participants were included in the review while twenty-nine studies were included in the Meta-Analysis for the prevalence of mortality. Studies with the prevalence of mortality and/or prevalence of comorbidity and prevalence of complications among hospitalized patients with COVID-19 were included and the characteristics of each included studies were described in (Table 1 ) and the rest were excluded with reasons (15, 17, 19, 27, 42, (50) (51) (52) (53) (54) (55) (56) (57) J o u r n a l P r e -p r o o f 

Twenty-nine studies reported prevalence and associated risk factors of mortality among hospitalized patients with coronavirus. The pooled prevalence of mortality was 15% (95% CI: 13 to 17, 29 studies, and 22924 participants) (Fig 2) . The subgroup analysis by country revealed that the mortality of patients with COVID-19 admitted in the hospital was the highest in USA followed by France 25% (95% CI: 19 to 30, 6 studies, 6032 participants) and 15% (95% CI: 9 to 22, one study, 124 participants) respectively (supplemental Fig 1) . 

The prevalence of mortality among hospitalized patients with COVID-19 in the Intensive Care Unit was 29% (95% CI: 20 to 38, 16 studies, 2227 participants) (Fig 3) . 

The Meta-Analysis revealed that the prevalence of comorbidity among hospitalized patients with COVID-19 was 48% (95% confidence interval (CI):35 to 62, 26 studies, 22528 participants) (Fig   4) . The subgroup analysis by the commonest comorbidities showed that diabetes mellitus was 48% (95% confidence interval (CI): 29 to 67, 3 studies, 117 participants) followed by hypertension and cardiovascular diseases 15% (95% confidence interval (CI):11 to 20, 14 studies, 8970 participants and 15% (95% confidence interval (CI): 8 to 21, 6 studies, 2505 participants) respectively (Fig 5) . 

Plenty of complications were mentioned in included studies including Acute Respiratory distress syndrome, acute kidney injury, sepsis, liver dysfunction, arrhythmia was the amongst reported as the common complications. The overall pooled prevalence of complications among hospitalized with COVID-19 was 36% (95% confidence interval (CI): 28 to 43, 16 studies, 8280 participants (Fig 6) . The Meta-Analysis revealed that sepsis was the most prevalent complication, 55% (95% confidence interval (CI):49 to 61, 2 studies, 246 participants) followed by Liver dysfunction and ARDS, 32% (95% confidence interval (CI): 23 to 44, one study, 77 participants and 26% (95% confidence interval (CI): 9 studies, 2524 participants) respectively (Fig 7) . 2) .

Sensitivity analysis was conducted to identify the most influential study on the pooled summary 

The total laboratory confirmed infected cases and the death of patients with SARS-CoV-2 virus is unpredictably high as compared to the previous two outbreaks (15, 17, 18, 27, 29, 54, 56, 84 (15, 17, 18, 27, 29, 54, 56, 84) . The possible explanation for a high number of deaths among hospitalized patients with COVID-19 may be explained in terms of disease severity, presence of co-morbidities, inadequate laboratory investigation, complications, and some others. However, the finding of this review is higher than other systematic reviews conducted among patients with COVID-19 and this discrepancy might be due to the inclusion of plenty of studies (37, (85) (86) (87) .

The subgroup analysis showed that the prevalence of in-hospital mortality among COVID-19

patients was higher in the USA followed by France and China. This higher prevalence of inhospital mortality in the USA compared to China might be due to the inclusion of a small number of studies from America as compared to china.

The Meta-Analysis revealed that the overall prevalence of comorbidities among patients hospitalized with COVID-19 was very high as compared to other systematic reviews and Meta-Analysis conducted to investigate the prevalence of comorbidity among COVID-19 patients (37, (86) (87) (88) . This dissimilarity might be due to the inclusion of plenty of studies in this systematic review. The Meta-analysis also revealed that the prevalence of hypertension, diabetes mellitus, cardiovascular disease, and respiratory disease which is comparable to other Meta-Analysis (37, (86) (87) (88) .

The systematic review showed that the prevalence of mortality among ICU admitted cases with Coronavirus was very high which is in line with systematic reviews conducted among hospitalized patients with COVID-19 (37, (85) (86) (87) .

The overall pooled prevalence of complications among hospitalized with COVID-19 was 36%

(95% confidence interval (CI): 28 to 43, 16 studies. The subgroup analysis showed that sepsis was the highest prevalent followed by liver dysfunction and ARDS, unlike other systematic J o u r n a l P r e -p r o o f reviews where ARDS was the most prevalent complication. This discrepancy might be due to the number of included studies and sample size contribution.

The prevalence of mortality among patients with co-morbidities, history of smoking, gender, advanced age, and others was very high. Acute respiratory distress syndrome was the most likely independent predictor of in-hospital mortality.

The systematic review and meta-analysis included plenty of studies with adequate sample size.

The methodological quality of included studies was moderate to high quality as depicted with

Joanna Briggs Institute assessment tool for meta-analysis of cross-sectional studies. However, substantial heterogeneity associated with dissimilarities of included studies in sample size, study setting, study design may limit generalization of this finding to the global community.

The review incorporated plenty of studies with a large number of participants but some of the included studies in this review didn't report risk factors, comorbidities, and complications for factor analysis. The included studies were conducted in a different setting with different sample sizes, population, and study design which caused substantial heterogeneity. Besides, there were a limited number of studies in some countries and it would be difficult to provide conclusive evidence with results pooled from fewer studies.

The current COVID-19 pandemic is spreading swiftly around the world due to uncertain mode of transmission, lack of proven treatment and vaccination, incompliance of people with preventive measures. Body of evidence revealed that the global prevalence of mortality, morbidity, and complications among hospitalized patients with COVID-19 was very high. The magnitude of this problem will be worse than this particularly in low and middle-income countries with weak health care systems and lack of well-equipped hospitals, ICU, skilled health care providers, quarantine centers, and laboratory centers. Therefore, global unity is highly required than ever to combat this deadly pandemic from the globe.

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The Meta-analysis revealed that the global prevalence of mortality, morbidity, and complications among hospitalized patients with COVID-19 was very high and the major independent predictors were identified. However, the included studies were too heterogeneous, and cross-sectional studies also don't show temporal relationship outcomes and their determinants. Therefore, further observational and randomized controlled trials are in demand for specific comorbidity by stratifying the possible independent predictors.

The systematic review and Meta-Analysis revealed that the prevalence of mortality among 

Ethical clearance and approval were obtained from the ethical review board of the XXXXXXXX

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Data and material can be available where appropriate.

-The review revealed that more than fifteen percent of patients admitted to the hospital with coronavirus died -The rate mortality among COVID-19 patients in the Intensive Care Unit was Twenty-nine percent -The Meta-Analysis revealed that sepsis was the most prevalent complication -Rate of mortality among COVID-19 was eight times more likely in patients with ARDS J o u r n a l P r e -p r o o f

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