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COVID-19 Case Fatality Rate and Factors Contributing to Mortality in Ethiopia: A Systematic Review of Current Evidence

Jul 4, 2022

COVID-19 patients. Publication date: From 2020 to 2022. [accessible before May 01, 2022]. Types of articles: Only full-text articles were included. Study Selection, Extraction, and Quality Assessment Prior to data abstraction, the extraction format was prepared. The data extraction template includes the author’s name, year of publication, study design, study area, source of data, sample size, and outcomes reported relevant to the current review. Full copies of articles identified by the search and meeting the inclusion criteria based on the title, abstract, and text contents are obtained for data synthesis. Two reviewers (DG and LA) – independently assessed studies for potential relevance, applied the eligibility criteria to the results – and did quality assessment independently for the included studies using the Newcastle-Ottawa Quality assessment scale adapted for observational studies 24 ( Table 1 ). Any disagreements in the evaluation of studies were resolved through consensus among the authors. Table 1 The Newcastle Ottawa Scale Quality Assessment Results of the Included Studies The Synthesis The systematic review approach was used to synthesize the evidence from the included studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline was followed to screen the studies. Review Question What are the contributing factors to mortality among COVID-19 patients in Ethiopia? Case Fatality Rate (CFR) Calculation In this review, CFR was defined as the proportion of COVID-19 cases with the outcome of death within a given period and calculated as follows. Contributing Factors In this review, they are explanatory variables that have been reported to heighten the risk of mortality from COVID-19 infection in selected studies with a p-value < 0.05. Results Description of the Searching and Screening Results A total of 793 records were retrieved through electronic databases search and other sources, and 560 records were removed due to duplication. Then, of the 233 original articles identified, 190 were removed because of irrelevant titles, abstracts, and texts. For the full-text review, 43 articles were selected, of which 30 articles were removed due to the inapt study place and pre-specified criteria. Finally, 13 studies were considered in the study ( Figure 1 ). Figure 1 PRISMA flow chart of the included study. Notes: Adapted from: Page MJ, McKenzie JE, Bossuyt PM, Boutron I et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71. 56 Creative Commons Attribution (CC BY 4.0) license ( https://creativecommons.org/licenses/by/4.0/legalcode ). Characteristics of the Included Studies A total of thirteen studies 25–37 were included in the review. All studies had been published between 2020 and 2022 with sample sizes ranging from 33 to 4398. Four studies were done in Addis Ababa, 26 , 28 , 33 , 35 three were in Oromia region, 29 , 36 , 37 two were in Amhara region, 27 , 31 one study was in Benishangul-Gumuz region, 30 one study was in Harari region, 34 one study was in Tigray region, 32 and one study was at national level. 25 Besides, study design included was one case-control, 26 six cohorts, 28–30 , 32–34 and six cross-sectionals. 25 , 27 , 31 , 35–37 Moreover, from the encompassed studies, seven reported on both case fatality rate and factors contributing to COVID-19 mortality, 28 , 30–34 , 37 whereas, five reported only a case fatality rate, 25 , 27 , 29 , 35 , 36 and one reported only on factors contributing to COVID-19 mortality, 26 and ( Table 2 ). Table 2 Characteristics of the Included Studies The Proportion of Case Fatality Rate Of the eligible studies, only one study did not report the proportion of CFR due to the nature of the study design. 26 However, all the other included studies have reported the CFR. 25 , 27–37 Accordingly, the present study confirmed the CFR of COVID-19 in Ethiopia ranges from nearly 1–20% ( Table 3 ). Table 3 Proportion of COVID-19 Case Fatality Rate Factors Contributing to Mortality Among COVID-19 Patients In this review, of the total included studies, eight reported the factors contributing to mortality from COVID-19 in the Ethiopian population. 26 , 28 , 30–34 , 37 As a result, we found that the presence of a high rate of one or more comorbid conditions was significantly associated with COVID-19 mortality and/or poor treatment outcome. 26 , 28 , 30 , 32–34 , 37 Furthermore, non-modifiable risk factors such as sex (being male) 30 and older age group 30–33 , 37 were among the factor contributing to mortality from COVID-19 disease. Additionally, behavioral risk factors such as smoking 34 and alcohol drinking history 34 were found to heighten mortality among confirmed COVID-19 patients in Ethiopia. As well, clinical manifestations and disease severity factors such as oxygen saturation level, 28 , 34 lymphocyte count, 33 , 34 worsening conditions, 37 abnormal sodium level, 33 shortness of breath, 26 , 28 and fever 26 were also identified to increase the likelihood of death from COVID-19 disease. Another important finding was that having a history of surgery/trauma 32 increases the chance of mortality among confirmed COVID-19 patients in the country ( Table 4 ). Table 4 Factors Contributing to COVID-19 Mortality in Ethiopia at p-value <0.05 Discussion This study systematically reviewed the available literature to identify the CFR of COVID-19 and factors contributing to mortality in Ethiopia. Thus, based on 13 studies that fulfilled eligibility criteria, the CFR of COVID-19 in Ethiopia ranges from nearly 1–20% among case-confirmed patients. Subsequently, despite the existence of limited evidence on COVID-19 CFR, some primary studies have reported CFR in different settings with various populations. For instance, a study reported from the Tigray region showed a 0.8% CFR among quarantined patients, 32 while a study from Addis Ababa stated a 5.3% CFR among prospectively admitted patients. 28 Additionally, surveillance data from the Oromia region revealed 1.2% CFR among all case-confirmed individuals. 36 In contrast to earlier findings, a high CFR of 20.2% and 19.0% were reported in Benishangul-Gumuz 30 and Harari 34 regions from retrospective medical record reviews, respectively. These inconsistencies might be due to case/death findings and reporting capacity, 38 , 39 and differences in healthcare practice and preventive strategies. 39 , 40 Furthermore, variation in CFR will be attributed to outcome ascertainment procedures, patient recruitment techniques, eligibility criteria, region location, and access to information. This study suggests that COVID-19 mortality and/or poor treatment outcome were high among patients with one or more comorbid conditions like diabetes, Asthma, COPD, hypertension, malignancy, CKD, and HIV infection. 26 , 28 , 30 , 32–34 , 37 The study from Nigeria also confirmed that hypertension, diabetes, renal disease, cancer, and HIV infection were predicted deaths among COVID-19 patients. 41 Furthermore, the current systematic review indicates that the higher the prevalence of comorbidities like heart disease, hypertension, and diabetes, the more likely the COVID-19 patient will require intensive care or will die. 42 Obesity, COPD, and CVD were also found to be risk factors for mortality among hospitalized COVID-19 patients in another systematic review. 43 Thus, patients with comorbidities should take all precautions to avoid COVID-19 infection, as their prognosis is usually the worst. 44 This review confirmed that non-modifiable risk factors such as sex (being male) 30 and older age group 30–33 , 37 were risk factors for COVID-19 mortality. Similarly, recent studies also reported older age groups are at a higher risk of dying from COVID-19 infection. 43–45 This is because older age groups have a higher rate of occurrence of comorbid conditions than younger age groups, exacerbating fatal outcomes. Besides, the findings from Italy, Nigeria, and the current review revealed males were at higher risk of fatality. 41 , 43 , 45 Aside from men’s greater contribution to comorbidities, the reasons for their higher fatality consist of behavioral, social, and biological variances that favor women. 46 As a result, maintaining high-quality sex-disaggregated data is required to monitor these disparities via ensuring unbiased testing and covering population subgroups from all socioeconomic strata. 47 Other important findings of this study were, behavioral risk factors like smoking 34 and alcohol drinking 34 were found to heighten mortality among COVID-19 patients in Ethiopia. Comparably, cigarette smoking was found to be a risk factor for mortality in a recent systematic review and study from China. 43 , 48 This is because, smoking alters the structure of the respiratory tract and decreases the immune response, both systemically and locally within the lungs, increasing the risk of infections. 49 A study from the UK showed that alcohol consumption has a negative effect on the progression of COVID-19 in white participants with obesity. 50 However, a finding from China reported alcohol has no significant effect on the development of severe illness/death in general COVID-19 patients. 48 In addition, another study from China reported that drinkers/smokers had a higher risk of severe COVID-19 but no higher risk of poor clinical outcomes. 51 Even though alcohol drinking exaggerates organ diseases like liver and heart, increasing the risk of disease severity, 50 the relationship between alcohol drinking and COVID-19 mortality should be further investigated. As well, clinical manifestations and disease severity factors such as oxygen saturation level, 28 , 34 lymphocyte count, 33 , 34 worsening conditions, 37 abnormal sodium level, 33 shortness of breath, 26 , 28 and fever 26 were also identified to increase the likelihood of death from COVID-19 disease. These findings were aligned with studies from Nigeria, 41 China, 48 Peru, 52 and France. 53 This is due to those factors leading to the onset of clinical signs and symptoms shows the advancement of severe and critical progression to poor clinical outcomes/death. Another important finding was, having a history of surgery/trauma 32 increases the chance of mortality among confirmed COVID-19 patients in the country. This also accords with other earlier studies from Italy 54 and Iran. 55 This can be due to challenges in the identification and management of surgical site infection in COVID-19 patients, and hospitalization stays. Moreover, the presence of pulmonary and thrombotic complications increased the risk of mortality in COVID-19 patients who underwent surgery. 54 Strengths and Limitations The strengths of our study include the application of explicit eligibility criteria, conduct of a comprehensive search, and novelty as there is no prior countrywide review exists. We would also like to acknowledge the main limitations of this study. First, our findings are mainly based on studies that recruited patients from health facilities and therefore, may be biased towards out-of-hospital mortality. Second, since the vast majority of the comprised studies were from medical record reviews, there could have been bias in the interpretation of the medical records and from unmeasured potential confounders. Despite these limitations, we believe that this review provides essential evidence on the current practice and future direction for COVID-19 patients in Ethiopia. Conclusion This study shows that the range of CFR of COVID-19 in Ethiopia is almost equivalent to other countries, despite the country’s low testing capacity and case detection rate in reference to its total population. Comorbid diseases, older age group, male sex, cigarette smoking, alcohol drinking, clinical manifestations and disease severity, and history of surgery/trauma were factors contributing to COVID-19 mortality in Ethiopia. Therefore, given the alarming global situation and rapidly evolving large-scale pandemics, urgent interdisciplinary interventions should be implemented in those vulnerable groups to lessen the risk of mortality. Furthermore, the CFR of COVID-19 should be estimated from all treatment and rehabilitation centers in the country, as underestimation could be linked to a lack of preparedness and mitigation. A large set of prospective studies are also compulsory to better understand the CFR of COVID-19 in Ethiopia. Paper Context Considerable numbers of articles on COVID-19 CFR have been published in Ethiopia. However, it is unreasonable to expect clinicians, public health experts, and the general population to read all the existing evidence on this theme. Thus, this study effectively summarizes existing evidence on COVID-19 CFR and factors contributing to mortality in Ethiopia. Consequently, implementing mitigation strategies for the synthesized factors that contribute to mortality should be emphasized urgently in order to combat the ongoing death. Data Sharing Statement Author Contributions All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work. Funding Disclosure References 1. World Health Organization. Coronavirus (COVID-19) [Internet]; 2022 [cited March 24, 2022]. Available from: https://www.who.int/health-topics/coronavirus#tab=tab_1 . Accessed . 5. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi:10.1016/S0140-6736(20)30183-5 6. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: a review. Clin Immunol. 2020;215:108427. doi:10.1016/j.clim.2020.108427 7. Elhiny R, Al-Jumaili AA, Yawuz MJ. An overview of post-COVID-19 complications. Int J Clin Pract. 2021;75(10):1–2. doi:10.1111/ijcp.14614 8. Huang D, Lian X, Song F, et al. Clinical features of severe patients infected with 2019 novel coronavirus: a systematic review and meta-analysis. Ann Transl Med. 2020;8(9):576. doi:10.21037/atm-20-2124 9. Ascencio-Montiel IJ, Tomás-López JC, Álvarez-Medina V, et al. A multimodal strategy to reduce the risk of hospitalization/death in ambulatory patients with COVID-19. Arch Med Res. 2022:1–6. doi:10.1016/j.arcmed.2021.07.002 10. Chavda VP, Apostolopoulos V. Mucormycosis – an opportunistic infection in the aged immunocompromised individual: a reason for concern in COVID-19. Maturitas. 2021;154:58–61. doi:10.1016/j.maturitas.2021.07.009 11. Girum T, Lentiro K, Geremew M, Migora B, Shewamare S, Shimbre MS. Optimal strategies for COVID-19 prevention from global evidence achieved through social distancing, stay at home, travel restriction and lockdown: a systematic review. Arch Public Health. 2021;79(1):1–18. 12. World Health Organization. Advice for the public: coronavirus disease (COVID-19) [Internet]; 2021 [cited March 25, 2022]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public . Accessed . 13. Liu J, Liu S. The management of coronavirus disease 2019 (COVID‐19). J Med Virol. 2020;92:1–7. 14. Singhal T. A review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020;87(4):281–286. doi:10.1007/s12098-020-03263-6 15. Chavda VP, Patel AB, Vaghasiya DD. SARS‐CoV‐2 variants and vulnerability at the global level. J Med Virol. 2022;94(7):2986–3005. doi:10.1002/jmv.27717 16. Islam S, Islam T, Islam MR. New coronavirus variants are creating more challenges to global healthcare system: a brief report on the current knowledge. Clin Pathol. 2022;15:2632010X2210755. doi:10.1177/2632010X221075584 17. WHO Africa. First case of COVID-19 confirmed in Ethiopia | WHO | Regional Office for Africa [Internet]; 2020 [cited April 28, 2021]. Available from: https://www.afro.who.int/news/first-case-covid-19-confirmed-ethiopia . Accessed . 21. Mohammed H, Oljira L, Roba KT, Yimer G, Fekadu A, Manyazewal T. Containment of COVID-19 in Ethiopia and implications for tuberculosis care and research. Infect Dis Poverty. 2020;9(1):1–8. doi:10.1186/s40249-020-00753-9 22. Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and characteristics of patients dying in relation to COVID-19 in Italy. J Am Med Assoc. 2020;323(18):1775–1776. 23. Akbari M, Fayazi N, Kazemzadeh Y, et al. Evaluate the Case Fatality Rate (CFR) and Basic Reproductive Rate (R-naught) of COVID-19. Curr Health Sci J. 2021;47(2):274. 24. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–605. doi:10.1007/s10654-010-9491-z 25. Gebremariam BM, Shienka KL, Kebede BA, Abiche MG. Epidemiological characteristics and treatment outcomes of hospitalized patients with COVID-19 in Ethiopia. Pan Afr Med J. 2020;37(Suppl 1):7. doi:10.11604/pamj.supp.2020.37.1.24436 26. Leulseged TW, Maru EH, Hassen IS, et al. Predictors of death in severe COVID-19 patients at millennium COVID-19 care center in Ethiopia: a case-control study. Pan Afr Med J. 2021;38:351. doi:10.11604/pamj.2021.38.351.28831 27. Abdela SG, Abegaz SH, Demsiss W, Tamirat KS, van Henten S, van Griensven J. Clinical profile and treatment of covid-19 patients: experiences from an Ethiopian treatment center. Am J Trop Med Hyg. 2021;104(2):532–536. doi:10.4269/ajtmh.20-1356 28. Leulseged TW, Hassen IS, Maru EH, et al. 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Clinical features and risk factors associated with morbidity and mortality among patients with COVID-19 in northern Ethiopia. Int J Infect Dis. 2021;105:776–783. doi:10.1016/j.ijid.2021.03.037 33. Leulseged TW, Hassen IS, Ayele BT, et al. Laboratory biomarkers of COVID-19 disease severity and outcome: findings from a developing country. PLoS One. 2021;16(3):e0246087. doi:10.1371/journal.pone.0246087 34. Ayana GM, Merga BT, Birhanu A, Alemu A, Negash B, Dessie Y. Predictors of mortality among hospitalized COVID-19 Patients at a Tertiary Care Hospital in Ethiopia. Infect Drug Resist. 2021;14:5363–5373. doi:10.2147/IDR.S337699 35. Teklu S, Sultan M, Azazh A, et al. Clinical and socio-demographic profile of the first 33 COVID-19 cases treated at dedicated treatment center in Ethiopia. Ethiop J Health Sci. 2020;30(5):645–652. doi:10.4314/ejhs.v30i5.2 36. Gudina EK, Gobena D, Debela T, et al. COVID-19 in Oromia Region of Ethiopia: a review of the first 6 months’ surveillance data. 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