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

Introduction

The recently emerged novel coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus, which spreads in small liquid particles from an infected person’s mouth or nose when they cough, sneeze, speak, sing, or breathe.¹ Currently, the ongoing COVID-19 infection was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020,² following the first case reported in Wuhan City, China, in December 2019.³ Since then, there have been more than 474 million confirmed COVID-19 cases worldwide, with about 6 million deaths as of March 24, 2022.⁴

COVID-19 causes clusters of fatal pneumonia.⁵ Thrombosis and pulmonary embolism have also been reported in severe cases.⁶ Additionally, lung abnormalities, neurological complications, and workout intolerance are commonly noted complications among survivors.⁷ Patients die due to multiple organ failure, shock, acute respiratory distress syndrome, heart failure, anemia, arrhythmias, secondary infection, and renal failure.^5,8 Additionally, male sex, older age, history of obesity, hypertension, diabetes,⁹ and immunosuppression (opportunistic infection)^9,10 were associated with an increased risk of hospitalization/death.

Despite those complications – as mitigating activities –keeping social distance and lockdown,⁶ staying at home and restricting travel,¹¹ wearing a properly fitted face mask, and cleaning hands frequently with sanitizer or soap and water¹² have been implemented to alleviate the further spread of the virus. Besides, early diagnosis, immediate isolation, general and optimized supportive care, and infection prevention and control were identified as significant aspects of COVID-19 management.¹³ Furthermore, getting vaccinated has been stated as an additional action to circumvent the burden of COVID-19. Thus, a total of more than 10.9 billion vaccine doses had been administered as of March 17, 2022.⁴

On the other hand, even though several options are being implemented to combat this pandemic, its global impact is still uncertain.¹⁴ Viral mutation,¹⁵ the emergence of new variants and resistance, and unclear routes of transmission¹⁶ are the major challenges the health system is facing to control the pandemic. The difficulties in accessing oxygen, medication, vaccination, and medical devices pose an additional threat to developing countries ability to control the pandemic.¹⁶

In Ethiopia, the Federal Ministry of Health has confirmed the first COVID-19 case on March 13th.¹⁷ As of March 24, 2022, the country tested more than 4 million suspects, which is below 4% of the country’s population,^18,19 of whom 469,523 (10.16%) cases had been confirmed positive and of these, 7491 (1.6%) died, 429,269 (91.4%) recovered, and 32,784 (7%) currently infected.¹⁹ Besides, the actual number of cases is likely to be much higher than the number of confirmed cases due to limited testing capability and challenges in the attribution of the cause of death.²⁰

The Federal Government of Ethiopia took numerous progressive activities to fight the COVID-19 pandemic. These include; public gatherings suspension, transports restriction, flight suspension, land borders closed, an apology for prisoners, election postponed, state of emergency stated, political parties and religious leaders participated, media informed the public, international alliances allied, and consistent information spreading.²¹ Furthermore, as of March 17, 2022, Ethiopia had administered more than 29 million doses of the COVID-19 vaccine as a prevention strategy.¹⁸

The CFR is one of the most important parameters for understanding the epidemiological features of an outbreak. The CFR of COVID-19 is defined as the number of deaths in COVID-19 cases divided by the total number of people infected by COVID-19.²² This rate is used in describing the mortality process and its overall changes, deciding on health priorities, allocating resources, designing intervention programs, and evaluating and refining problems and programs related to public health and disease epidemics.²³

As the threat of COVID-19 persisted, one of the issues that needed to be addressed is identifying the CFR and the key factors contributing to mortality. In Ethiopia, despite a number of primary studies have been conducted to estimate the CFR of COVID-19, no review study has attempted to summarize this evidence to better understand the nature of an outbreak and the virulence of the disease. Therefore, it is critical to summarize and uncover discrepancies in the primary results. The finding of this study is essential for preventing further COVID-19 mortality by identifying and enabling action on the summarized factors that contribute to mortality.

Methods

Search Strategy

This review was conducted to summarize the CFR of COVID-19 and factors contributing to mortality from primary studies done in Ethiopia. As a result, different electronic databases such as PubMed, Science Direct, CINAHL, SCOPUS, Hinari, and Google Scholar were systematically searched. Additionally, other sources such as GOOGLE, journal homepages, and bibliographies were searched to retrieve eligible studies. The search terms were used as keywords and MeSH terms both individually and in conjunction with the “OR” and “AND” Boolean operators. Thus, (“COVID-19”[Mesh] OR “SARS-CoV-2”[Mesh] OR “Corona virus”[tw] OR “COVID-19 positive”[tw] OR “COVID-19 patient*”[tw]) AND (Mortality[tw] OR “Treatment Outcome”[tw] OR fatality[tw] OR Survival[tw] OR “factors associated”[tw] OR predictor OR “Risk Factors”[Mesh]) AND (Ethiopia*[tw]) were used. The Mendeley software was used to save and remove the duplicated record search results.

Eligibility Criteria

Study design: observational studies that have reported CFR of COVID-19 and/or factors contributing to mortality among

COVID-19 patients.

Language: Articles published in the English language.

Publication date: From 2020 to 2022. [accessible before May 01, 2022].

Types of articles: Only full-text articles were included.

Setting: Studies conducted in Ethiopia.

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 studies²⁴ (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

1. What is the range of COVID-19 CFR in Ethiopia?
2. 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 smoking³⁴ and alcohol drinking history³⁴ 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 fever²⁶ were also identified to increase the likelihood of death from COVID-19 disease. Another important finding was that having a history of surgery/trauma³² 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-Gumuz³⁰ and Harari³⁴ 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 smoking³⁴ and alcohol drinking³⁴ 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 fever²⁶ 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/trauma³² increases the chance of mortality among confirmed COVID-19 patients in the country. This also accords with other earlier studies from Italy⁵⁴ 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.