Abdella et al.

BMC Infect Dis (2021) 21:956

https://doi.org/10.1186/s12879-021-06652-0

STUDY PROTOCOL Open Access

Prognostic factors and outcomes

of COVID‑19 cases in Ethiopia: multi‑center
cohort study protocol
Saro Abdella1, Masresha Tessema1* , Geremew Tasew1, Atkure Defar1, Asefa Deressa1, Feyisa Regasa1,
Frehiwot Teka1, Eyasu Tigabu1, Dereje Nigussie1, Tefera Belachew6, Million Molla7, Amare Deribew8,
Workeabeba Abebe9, Tegbar Yigzaw10, Tsinuel Nigatu11, Getnet Mitike4, Tewodros Haile9, Haftom Taame12,
Muhammed Ahmed1, Frehiwot Nigatu4, Tola Tolesa3, Eskinder Wolka4, Wondwossen Amogne3,
Arnaud Laillou13, Misker Amare1, Yaregal Fufa1, Alemayehu Argaw6, Woldesenbet Waganew16, Akilili Azazh16,
Aschalew Worku16, Berhane Redae16, Menbeu Sultan16, Miraf Walelegn16, Muluwork Tefera16, Sisay Yifru16,
Rahel Argaw16, Natinael Brehau2, Sisay Teklu16, Getachew Demoz2, Yakob Seman16, Mihretab Salasibew14,
Eshetu Ejeta1, Susan J. Whiting15, Dawit Wolday5, Getachew Tollera1, Ebba Abate1 and Dereje Duguma16

Abstract
Background: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus
(SARS-CoV-2) and became pandemic after emerging in Wuhan, China, in December 2019. Several studies have been
conducted to understand the key features of COVID-19 and its public health impact. However, the prognostic factors
of COVID-19 are not well studied in the African setting. In this study, we aim to determine the epidemiological and
clinical features of COVID-19 cases, immunological and virological courses, interaction with nutritional status, and
response to treatment for COVID-19 patients in Ethiopia.
Methods: A multi-center cohort study design will be performed. Patients with confirmed COVID-19 infection admit-
ted to selected treatment centers will be enrolled irrespective of their symptoms and followed-up for 12 months.
Baseline epidemiological, clinical, laboratory and imaging data will be collected from treatment records, interviews,
physical measurements, and biological samples. Follow-up data collection involves treatment and prognostic out-
comes to be measured using different biomarkers and clinical parameters. Data collection will be done electronically
using the Open Data Kit (ODK) software package and then exported to STATA/SPSS for analysis. Both descriptive and
multivariable analyses will be performed to assess the independent determinants of the treatment outcome and
prognosis to generate relevant information for informed prevention and case management. The primary outcomes of
this study are death/survival and viral shedding. Secondary outcomes include epidemiological characteristics, clinical
features, genetic frequency shifts (genotypic variations), and nutritional status.
Discussion: This is the first large prospective cohort study of patients in hospitals with COVID-19 in Ethiopia. The
results will enable us to better understand the epidemiology of SARS-CoV-2 in Africa. This study will also provide

*Correspondence: masresha88@gmail.com
1
Ethiopian Public Health Institute, Addis Ababa, Ethiopia
Full list of author information is available at the end of the article

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Abdella et al. BMC Infect Dis (2021) 21:956 Page 2 of 7

useful information for effective public health measures and future pandemic preparedness and in response to out-
breaks. It will also support policymakers in managing the epidemic based on scientific evidence.
Trial Registration: The Protocol prospectively registered in ClinicalTrials.gov (NCT04584424) on 30 October, 2020.
Keywords: COVID-19, Prognostic Factors, Outcomes of COVID, Cohort, Ethiopia

Background [9], and genetic conditions [10]. However, a compre-

On March 11, 2020, the World Health Organization hensive understanding of the underlying immunologi-
(WHO) declared Corona Virus Disease (COVID-19) to cal process, particularly within cellular immunity, is still
be a pandemic [1]. The current new emerging virus is a not well defined. The clinical disease spectrum of the
different strain of virus from SARS and MERS CORONA SARS COV-2 ranges from subclinical or manifesting as
viruses. The difference is not only limited to genetic unremarkable respiratory symptoms to severe respira-
makeup but also in the clinical presentations, case fatal- tory complications such as pneumonia and respiratory
ity, and the rate of spread across the globe (surveillances). distress.
The swift spread of the virus is largely attributed to its There is growing literature highlighting obesity as
stealth transmission, for which infected patients may a significant risk factor for the development of severe
be asymptomatic or exhibit only flu-like symptoms in COVID-19. Body mass index (BMI) is an anthropomet-
the early stage. These undetected transmissions present ric measure used to assess obesity risk and has been
a remarkable challenge for the containment of the virus observed as a risk factor in MERS-CoV [11] and influ-
and pose an appalling threat to public health [2]. COVID- enza [12]. A recent systematic review showed that high
19 has become one of the leading causes of mortality BMI plays a significant role in COVID-19 severity in all
around the world. ages, especially in the elderly population [13]. Obesity is
As of August 03, 2021, there have been 200,508,148 associated with increased severity and mortality in pan-
confirmed cases and 4.26 million deaths reported world- demic H1N1 influenza and other respiratory viruses [14].
wide and nationally 281,300 confirmed cases and 4,395 With the currently available evidence so far, children
deaths reported [3]. To this end, the COVID-19 Global contribute 1–5% of total COVID-19 cases worldwide
Research and Innovation Forum recommended each [15]. Asymptomatic disease in SARS-CoV-2 positive chil-
country and region to conduct research and generate evi- dren ranged from 13% in China to 21% in Italy. Clinical
dence in their respective local context to strike the right features in symptomatic children are generally milder
balance between stopping transmission now and prepare than adults; a very small proportion of those aged under
for the future [4]. 19 years have developed severe (2.5%) or critical disease
COVID-19 has also sparked fears of an impending eco- (0.2%) [16].The USA and Chinese data showed bimodal
nomic crisis and recession [5]. Social distancing, self-iso- age distribution among critically ill children, infants and
lation and quarantine, travel restrictions and border shut adolescents > 15 years were more likely to be hospitalized
downs have led to a reduced workforce across all eco- due to COVID-19, and death was extremely rare with
nomic sectors and caused many jobs to be lost. Schools only a few numbers of reported cases [17].
have been closed down, and the need for commodities Evidence on the effect of COVID-19 on pregnancy and
and manufactured products has decreased [6]. Along its outcomes seems to be controversial. In some stud-
with its high infectivity and fatality rates, there has been ies, pregnant mothers with confirmed COVID-19 infec-
mass fear of COVID-19, termed as “coronaphobia”, that tion were discharged without any major complications
has generated a plethora of psychiatric manifestations after giving birth. However, severe maternal morbid-
across the different strata of the society [7]. The COVID- ity resulting from COVID-19 and perinatal deaths has
19 itself, multiplied by forced quarantine to combat the been documented in other studies [18]. There is also
disease applied by nationwide lockdowns can produce limited evidence about in utero infection and early posi-
acute panic, anxiety, obsessive behaviors, hoarding, par- tive neonatal testing. For example, a prospective cohort
anoia, depression, and post-traumatic stress disorder study conducted among pregnant women admitted to
(PTSD) [7, 8]. the hospital with confirmed SARS-CoV-2 infection in
Several socio-demographic, clinical, immunological the UK revealed that 12 (5%) of 265 infants tested posi-
and nutritional factors are associated with COVID-19 tive for SARS-CoV-2 RNA, six of them within the first
disease progression. Evidence shows that COVID-19 12 h after birth [19]. Contrary to this, infection has not
disease progression is worse in people with suppressed been found in neonates delivered from pregnant women
immunity due to old age, pre-existing health conditions with COVID-19 based on a report from Hubei Province,
Abdella et al. BMC Infect Dis (2021) 21:956 Page 3 of 7

China [20]. Further research, therefore, is required to treatment on COVID-19 outcome among patients admit-
determine the effect of COVID-19 on pregnancy and ted to treatment centers in Ethiopia.
birth outcomes in our situation.
Nutrition is a key determinant of health [21]. More
importantly, it is part of the treatment regimen for acute Methods/design
and chronic diseases and applies particularly to ailments Aim and study setting
for which an etiologic treatment has not yet been dis- In this multi-site cohort study, we aimed to determine
covered and validated. An adequate diet is necessary to the natural history of the disease; clinical features and
provide energy for the body’s functions and nutrients management, epidemiological characteristics, immuno-
to build and repair tissues, prevent sickness, and help logical, virological courses and treatment response of the
the body heal from illness [22]. A balanced diet also disease, effects of diets on the nutritional status on the
has a vital role in bolstering the immune response of an disease progression, effect of the disease on pregnancy
infected person against RNA viral infections [23]. There and birth outcomes, and the effect of traditional/mod-
is sufficient evidence to demonstrate that the immune ern treatment on COVID-19 outcomes among patients
response can be weakened by inadequate nutrition [22, admitted to treatment centers in Ethiopia. Therefore,
23, 25]. The role of some nutrients in immune function the study findings will generate scientific data for a sys-
and infectious diseases is well established, such as vita- tematic understanding of natural history, epidemiologi-
min D [25]. cal characteristics, clinical features, and management
In recent studies, COVID-19 is shown to be commonly of COVID-19 which will, in turn, enable the country’s
complicated with coagulopathy, and the management of health sector to develop strategies to prevent and control
thromboembolism has significant importance in reduc- the pandemic before it poses further health and socioec-
ing mortality and morbidity [26, 27]. This indicates that a onomic crises. The research question of this study is “Do
severe cytokine storm induces SARS-Cov-2 to lead to the different individual host factors and environmental situ-
coagulation cascade, causing thromboembolism, which is ations influence clinical, epidemiological, and viral out-
linked to abnormal parameters such as increases in fibrin, comes of COVID-19 infection?”.
fibrin degradation products, fibrinogen, and D-dimer. The study will be conducted in all Federal treatment
Furthermore, immobility, systemic inflammation, plate- centers, including Ekakotebe, Yekatit-12, St. Peter Spe-
let activation, endothelial dysfunction, and stasis of blood cialized hospitals, SPHMMC, Millennium hall center in
flow have been reported as the predisposing factors of Addis Ababa, and Regional Hospitals including Mekelle,
thromboembolism [27]. The WHO recommended the Semera, Bahir Dar, Adama/Mojo, Hawassa, Jijiga, Harar,
use of low molecular weight heparin (e.g., enoxaparin), DireDawa, Metekel or Benishangul Gumuz, and Gamb-
according to local and international standards, to prevent ela dedicated to COVID 19 treatment.
venous thromboembolism, when not contraindicated
in COVID-19 patients [28]. However, the incidence of
venous thromboembolism in COVID-19 patients hospi- Study design and period
talized and under thromboprophylaxis is unclear. A multi-center prospective open cohort study design
To understand the negative impacts of COVID-19 on on COVID-19 confirmed cases in Ethiopia conducted
public health and key features pertinent to the disease, from December 01, 2020 to December 2021. Like many
various studies are under investigation at the global other disease-specific general open cohorts, such as in
level and they are contributing to delineating the char- Framingham Heart Study and the Ethiopia Netherlands
acteristics of the disease and its lethality. Currently, it is AIDS Research Project (ENARP) studies, the study
recognized that a ‘one size fits all’ approach towards the intends primarily to measure the incidence of several
design and implementation of interventions may not be epidemiological, clinical, virological, and immunological
appropriate. Therefore, global priorities, protocols, and outcomes of COVID-19 cases [29, 30]. The cohort will be
intervention assessments have to be contextualized and an unbiased extensive routine collection of clinical, radi-
adjusted to local needs and realities, including the trans- ographic, laboratory, and clinical management, virologi-
lation of results. Therefore, this study aimed to determine cal, immunological and nutritional data, which helps to
the natural history of the disease; clinical features and detect and address emerging research priorities without
management, epidemiological characteristics, immuno- relying on a priori hypothesis.
logical, virological courses and treatment response of the
disease; effects of diets on the nutritional status on dis- Study population
ease progression; effect of the disease on pregnancy and This study will enroll individuals with confirmed infec-
birth outcomes; and, the effect of traditional/modern tion with COVID-19 at selected Federal and Regional
Abdella et al. BMC Infect Dis (2021) 21:956 Page 4 of 7

Hospitals irrespective of their differences (age, sex, symp- measures; plasma 25-hydroxyvitamin D concentrations;
toms, severity, and any other conditions). The patients’ dietary history; micronutrient status (zinc and vitamin
follow-up will be done strictly within the management A); fasting blood sugar; weight, height, BMI; total choles-
adapted to their infection. terol (TC), triglycerides (TG), HDL-C, LDL-C and body
Individuals/patients in the study hospital or area will composition(waist circumference); genetic frequency
be eligible for inclusion if they meet the following crite- shifts (genotypic variations); obstetric and gynecologic
ria: (1) patient is admitted to selected treatment centers history; pregnancy status/test; clinical status; supplemen-
(Federal and Regional’s Hospitals) with COVID-19 con- tal oxygen; non-invasive ventilation or oxygen delivery
firmed by RT-PCR; and (2) consents to be enrolled in the devices/ respiratory support. We will also collect con-
follow-up study and provide all necessary information/ founding variables include socio-demographic variables
data, blood sample, and nasopharyngeal swab for testing. (age, sex, education status); status cases at the time of
Patients will be excluded if: (1) a subject deprived of free- enrollment; and months after the first positive test.
dom, subject under a legal protective measure; (2) refusal
by a participant, parent or appropriate guardian or repre- Data collection
sentative; (3) not willing to stay 12 months in the cohort Data collection will be done electronically using the
in Ethiopia; (4) is already involved in the COVID-19 clin- REDCap software package and data documentation will
ical trial or other interventional studies; (5) not capable be performed from a retrospective history of the patient
of understanding or complying with the study protocol or and prospectively after treatment is finalized. Contact
provide consent; (6) anticipated transfer to another hos- information such as home address and telephone number
pital that is not a study site within 72 h. will be collected to facilitate follow up and for tracking
defaulters of follow-up. For asymptomatic cases whose
Sample size and sampling procedures follow-up is undertaken at home, their home address,
The estimated sample size for this study is 6,390, based GPS coordinates and geospatial data for all participants
on the assumptions of a 28 percent death rate from a will also be registered by trained data collectors (study
retrospective study, a design effect of 2.5, and a 20 per- nurse or doctor). Data will be gathered from patients and
cent loss to follow-up. A baseline evaluation or assess- follow up cases through interviews by physicians/nurses
ment will be performed immediately after screening. at each treatment center using a questionnaire and stand-
After baseline assessment, all patients will be followed- ardized Case report form (CRF). Biological samples will
up daily until discharge according to WHO and National also be collected at baseline and follow up when sam-
discharging guideline and followed as per schedule after ples are taken in the context of care to meet the research
discharged. Study subjects enrolled will be followed up objectives. Five-milliliter venous blood will be collected
for 12 months after enrollment for the specific objective using a serum separator tube and 4 mL venous blood will
related to virology and immunology, clinical course of the be collected using a test tube containing anticoagulant.
disease, response to treatment, effect of COVID-19 in Viral load measures in a body fluid using Abbot and Rosh
pregnant mothers and birth-related effects of COVID-19. reagents and platforms will be measured. Phylogenetic
Enrolled cases will be followed up at 2 weeks, 3 months, analysis of SARS-CoV-2: genotyping of different types of
6 months, 9 months, and 12 months post-discharge. A SARS-CoV-2 from Ethiopian isolates under different set-
visit window of ± 7 days may be applied to these visits. tings will be done using a next-generation sequencer at
Patients discharged after recovery will be followed up Ethiopian Public Health Institute (EPHI). Imaging: chest
according to the follow-up schedule. x-ray, ultrasound scan, chest computed tomographic
(CT) scans data will be retrieved if available. Labora-
Primary outcome and secondary outcomes tory tests for D-dimers, platelet count, PT, PTT, INR, D-
The primary outcome variables are treatment outcome Dimer, and serum ferritin will be measured.
(active cases, recovered, death or transferred for further The screening will be performed within the period
treatment), recovery time, and duration of viral shedding between one to two days of admission to the hospital to
(the time from the first positive RT-PCR results to the review study inclusion/exclusion criteria; obtain prior
occurrence of the last positive RT-PCR results or nega- medical and concomitant medication histories; perform
tive RT-PCR results). The secondary outcomes include a complete physical examination, including height, body
clinical symptoms and signs (major); co-morbidities; weight, and vital signs (blood pressure, BP, heart rate,
status at last follow-up (survival, severity, virus detec- HR), Oxygen saturation (SpO2) with pulse oximetry; and
tion); laboratory biomarkers; duration of symptomatic collect a blood sample for laboratory testing on screening
phase, inpatient stay, ICU stay; viral loads; anti-SARS- day.
CoV-2 antibody titer; imaging with results; therapeutic
Abdella et al. BMC Infect Dis (2021) 21:956 Page 5 of 7

Baseline assessment (FEV1), forced vital capacity (FVC) and FEV1/FVC

The baseline assessment (day 1) will be scheduled imme- ratio,
diately after screening. At baseline, the following tasks • Collect blood for serum chemistries including creati-
will be performed: nine, electrolytes, total bilirubin, albumin, ALT, AST,
total protein, CK, calculate CrCl, Ab tests,
1. Review and record all prior workup or test results. • Collect mouth/nasal swabs for PCR tests,
2. Record detailed history of prior medication use in • Collect urine for analysis, including pregnancy test
the subject. (in women),
3. The query for signs and symptoms and updated • Collect serum on-site as the back-up storage (3 mL
medications used since the screening visit. Any serum) and
signs or symptoms reported after study drug • Collect dietary history.
administration should be recorded as adverse
events. Any signs or symptoms reported before the
study should be recorded as a pre-existing condi- Data processing and statistical analysis
tion but should be collected and recorded in detail. Data collection will be done electronically using the ODK
4. Perform a complete physical examination. software package and then exported to STATA/SPSS for
5. Obtain vital signs (HR, BP, RR, Oxygen saturation, data cleaning, management, and statistical analysis. The
capillary refill), Oxygen saturation (SpO2) with data will be cleaned and checked for outliers, all assump-
pulse oximetry. tions, and analyzed using appropriate statistical software
6. Obtain body height, weight, and waist circumfer- (STATA, Python, and/or R statistic software).The analysis
ence. will be performed by trained personnel (epidemiologists,
7. Obtain the dietary history of the patients. statisticians, health economists) using the appropri-
8. Collect urine for urinalysis, with the microscopic ate statistical methods. Statistical analyses strategy will
exam and for a pregnancy test (in women). be based on specific study objectives and the nature of
9. Collect blood for CBC and for serum chemis- the outcome variables, the various assumptions to be
tries including creatinine, total bilirubin, albumin, assessed and associated scenarios to be considered, and
ALT, AST, total protein, CK, Creatinine Clearance the criteria to be used for decision-making at each stage
(CrCl), and Ab assays, fasting blood sugar, lipid including management of incomplete data, model build-
profiles (TC, LDL, HDL and triglycerides), plasm ing procedures, and evaluating the validity of models
25-hydroxy vitamin D concentration, laboratory and the robustness of results. Data will be assessed for
test for D-dimers, platelet count, PT PPT, INR, and consistency, missing values, presence of outliers and
serum ferritin. implausible values, and different statistical assumptions
10. Collect serum (recommend 5 mL serum storage at including univariate and multivariate normality of distri-
the investigational site as a back-up specimen). butions, the linearity of hypothesized relationships, the
proportionality of hazard, and the presence of rare events
among others.
Follow‑up visits A descriptive summary of the continuous variables
Data collection at follow-up at 2 weeks, 3 months, will be reported as mean (± SD) and median (IQR), and
6 months, 9 months and 12 months was the same as at categorical variables will be summarized as counts and
baseline and used to ascertain primary and secondary percentages. A correlation or chi-square test will be per-
outcomes. The following tasks will be performed at these formed for appropriate variables.
visits: Predictors that have been identified as risk factors in
the bivariate analysis will be entered into multivariable
• Perform symptom-Directed physical exam, analysis to isolate independent determinants of the out-
• Obtain body weight and vital signs including pulse, come. Multiple linear and generalized linear regression
respiratory rate and blood pleasure, oxygen satura- models will be fitted depending on the type of outcome
tion, variable. Cox-proportional hazard ratio (HR) will be used
• Perform pulmonary function test (PFT), for time-to-event variables including the time to recov-
• Record any symptoms, ery, and other time to event variables. Time to event
• Spirometry to determine pulmonary function tests analysis, semi and parametric survival analysis will be
such as forced expiratory volume in the first second conducted as appropriate.
To take into account the multi-center cohort design,
i.e., clustering of data by treatment centers and repeated
Abdella et al. BMC Infect Dis (2021) 21:956 Page 6 of 7

measurements per subject over time, a multilevel mode- Acknowledgements

The authors would like to thank all study Hospitals and their staff.
ling approach will be employed using mixed-effects mod-
eling or generalized estimating equation. Incomplete data Study status
(missing values and lost-to-follow-up cases) will be han- The study participant recruitment has been started.
dled using model-based approaches, such as full infor- Authors’ contributions
mation maximum likelihood estimation and multiple SA, MT1, AD1, GT1, AD2, FR, FT, ET, GN have made substantial contributions to
imputation modeling after the missing data mechanisms the conception. SA, MT1, SW and EE have drafted the manuscript or substan-
tively revised it. GT2, EA, and DD have made substantial contribution to design
and assumptions are evaluated. Regression models will of work and supervised protocol development.AD3, DN, TB, MM, AD, WA1, TY,
be evaluated for potential problems including collinear- TN, GM, TH, HT, MA1, FN, TT, EW, WA2, AL, MA2, YF, AA1, WW, AA2, AW, BR, MS1,
ity among predictors, omitted variables bias, and model MW, MT2, SY, RA, NB, ST, GD, YS, MS2, DW, and DD were substantially contrib-
uted to design of work. All authors have approved the submitted manuscript;
over-adjustment (endogeneity). The final fitted mod- critically commented on manuscript and agreed both to be personally
els will be assessed for validity and robustness of results accountable for the author’s own contributions and to ensure that questions
on a subsample of data not used in the model-building related to the accuracy or integrity of any part of the work. All authors read
and approved the final manuscript.
procedure. For this purpose, a random subsample from
the original data will be kept before starting the analy- Funding
sis. Statistical significance will be considered at α < 0.05. This project is funded by the Ethiopian Ministry of Health and International
Institute for Primary Heath Care-Ethiopia. The funding bodies do not play a
However, to control for the inflated probability of Type- role in the design of the study and collection, analysis, nor in the interpreta-
I error due to multiple hypotheses testing, P-values will tion of data or in writing the manuscript.
be adjusted for false discovery rate using the Benjamini–
Availability of data and materials
Hochberg method. The results will be described as per- As this study is not started, data are not available at this time. De-identified
centages, tables, figures, and association significance. data will be available after publication of primary analyses, upon communica-
tion with the corresponding authors and according to the requirements of
applicable IRBs and institutional policies.

Discussion
Declarations
SARS-COV-19 pandemic has caused huge detrimental
impact in social interaction and economic aspects glob- Ethics approval and consent to participate
ally to an extent unseen before. Moreover, the health- This study has been approved by Ethiopian Public Health Institute Scientific
and Ethical Review Committee (EPHI-IRB-282-2020). Data of only consenting
care systems have become overloaded even in developed individuals will be analyzed and communicated. Informed oral consent will
countries. This is the first large prospective cohort study be obtained from each study participant. We obtained a waiver of signed
of patients in hospitals with COVID-19 in Ethiopia. The consent that the signature of participants will not be taken. This study poses
minimal risk for respondents (discomfort during interviews and blood collec-
results will enable us to better understand the epidemiol- tion). Moreover, a Participant Information Sheet (PIS) that explains the study
ogy of SARS-CoV-2 in an African setting. This study will objectives, potential benefits and risks, and types of data being collected were
also provide useful information for effective public health prepared to read aloud to all the respondents. Ascent will be sought from
participants whose age is less than 18 years. Each participant will be informed
measures and future pandemic preparedness and in about the objective of the study. Any participant involuntary to participate
response to outbreaks. It will also support policymakers in the study will not be forced to participate. They will also be informed that
in managing the epidemic based on scientific evidence. all data obtained from them will be kept confidential. Data collectors trained
by the principal and/or co-investigators will obtain either consent or ascent
depending on the age of the patient.Permission to conduct this study and
support letter will be obtained from the EPHI and Regional Health Bureaus.
Abbreviations
Participants will be approached through indexing cases and local health
COVID-19: Coronavirus Disease 2019; SARS-CoV: SARS Coronavirus; MERS-CoV:
authorities. Filled questionnaires and laboratory report documents will be kept
Middle Eastern Respiratory Syndrome Coronavirus; H1N1: Influenza A Virus
secured in a locked cupboard and electronically protected device. Participants
Subtype H1N1; RNA: Ribonucleic Acid; SPHMMC: Paul’s Hospital Millennium
will give their consent independently and privately for both interviews and
Medical College; RT-PCR: Reverse Transcription Polymerase Chain Reaction;
sample collection simultaneously. After capturing using a smartphone/tablet,
ICU: Intensive Care Unit; GPS: Global Positioning System; CT: Chest Computed
the signed informed consent/assent will be documented in a secured place
Tomographic; PT: Prothrombin Time; PTT: Thromboplastin Time; INR: Interna-
dedicated to this purpose. The electronic one will be kept in a password pro-
tional Normalized Ratio; HR: Heart Rate; BP: Blood Pressure ; SpO2: Oxygen
tected electronic machine. For children under 15, their parents or caregivers
Saturation; RR: Respiratory Rate; CBC: Complete Blood Count; ALT: Alanine
will be consented and also their contact.
Aminotransferase; CK: Creatine Kinase; AST: Aspartate Aminotransferase; CrCl:
Creatinine Clearance; FEV1: First Second of the Forceful Exhalation; FVC: Forced
Consent for publication
Vital Capacity; IQR: Inter Quartile Range; COVID: Corona Virus Disease; BMI:
Not applicable.
Body Mass Index; EPHI: Ethiopian Public Health Institute; rRT-PCRS: Reverse
Transcription Real Time Polymerase Chain Reaction; FVC: Forced Vital Capacity;
Competing interests
PFT: Perform Pulmonary Function Test; CRF: Standardized Case Report Form;
The authors declare that they have no competing interests.
TC: Total Cholesterol; LDL: Low-density Lipoprotein; PTSD: Post-traumatic
Stress Disorder; ENARP: Ethiopia Netherlands AIDS Research Project; SARS-
Author details
CoV-2: Severe Acute Respiratory Syndrome Coronavirus; ODK: Open Data Kit; 1
Ethiopian Public Health Institute, Addis Ababa, Ethiopia. 2 COVID‑19 Isolation
TG: Triglycerides; HDL-C: High-density Lipoprotein Cholesterol; LDL-C: Low-
and Treatment Center, Eka Kotebe General Hospital, Addis Ababa, Ethio-
density Lipoprotein Cholesterol.
pia. 3 Saint Paul’s Hospital, Addis Ababa, Ethiopia. 4 International Institute
Abdella et al. BMC Infect Dis (2021) 21:956 Page 7 of 7

for Primary Health Care, Addis Ababa, Ethiopia. 5 Mekelle University, Mek’ele, adults and children from influenza and other respiratory viruses. Influenza
Ethiopia. 6 Jimma University, Jimma, Ethiopia. 7 Saint Peter Hospital, Addis Other Respir Viruses. 2019;13(1):3–9.
Ababa, Ethiopia. 8 Nutrition International, Addis Ababa, Ethiopia. 9 Addis Ababa 15. Ludvigsson JF. Systematic review of COVID-19 in children shows
University, Addis Ababa, Ethiopia. 10 Jhpiego-Innovating, Addis Ababa, Ethio- milder cases and a better prognosis than adults. Acta paediatr.
pia. 11 Harvard T.H. Chan School of Public Health, Boston, MA, USA. 12 Africa 2020;109(6):1088–95.
CDC, Addis Ababa, Ethiopia. 13 UNICEF, Addis Ababa, Ethiopia. 14 Children’s 16. World Health Organization. Report of the WHO-China joint mission on
Investment Fund Foundation, London, UK. 15 College of Pharmacy and Nutri- coronavirus disease 2019 (COVID-19). Geneva: World Health Organization;
tion, University of Saskatchewan, Saskatoon, SK, Canada. 16 Ethiopian Ministry 2020.
of Health, Addis Ababa, Ethiopia. 17. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, et al.
SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663–5.
Received: 25 December 2020 Accepted: 1 September 2021 18. Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID-
19: A systematic review of 108 pregnancies. Acta Obstet Gynecol Scand.
2020;99(7):823–9.
19. Knight M, Bunch K, Vousden N, Morris E, Simpson N, Gale C, O’Brien P,
Quigley M, Brocklehurst P, Kurinczuk JJ. Characteristics and outcomes of
References pregnant women admitted to hospital with confirmed SARS-CoV-2 infec-
1. World Health Organization. WHO Director-General’s opening remarks tion in UK: national population based cohort study. BMJ. 2020;369:m2107.
at the media briefing on COVID19. Geneva: World Health Organization; 20. Zhang C, Wang XM, Li SR, Twelkmeyer T, Wang WH, Zhang SY, Wang SF,
2020. Chen JZ, Jin X, Wu YZ, et al. NKG2A is a NK cell exhaustion checkpoint for
2. Tian H, Liu Y, Li Y. An investigation of transmission control measures HCV persistence. Nat Commun. 2019;10(1):1507.
during the first 50 days of the COVID-19 epidemic in China. Science. 21. Covinsky K, Katz M. Supplemental nutrition assistance program-
2020;368(6491):638–42. do not take the food out of patients’ mouths. JAMA Intern Med.
3. Ethiopian Public Health IInstitute. Daily covid 19 updates. Addis Ababa: 2020;180(4):605–6.
Ethiopian Public Health IInstitute; 2020. 22. Chandra RK. Nutrition, immunity and infection: from basic knowledge
4. World Health Organization. A coordinated global research roadmap: 2019 of dietary manipulation of immune responses to practical application of
novel coronavirus. Geneva: World Health Organization; 2020. ameliorating suffering and improving survival. Proc Natl Acad Sci USA.
5. Bălan M, Pelinescu E: Effects of the Covid-19 pandemic on the labour 1996;93(25):14304–7.
market. Int J Latest Res Human Soc Sci 3(7).http://​www.​ijlrh​ss.​com/​paper/​ 23. Gibson RS. Principles of nutritional assessment. Oxford: Oxford University
volume-​3-​issue-7/​13-​HSS-​715.​pdf. Press; 2005.
6. Nicola M, Alsafi Z, Sohrabi C, Kerwan A, Al-Jabir A, Iosifidis C, Agha M, 24. Shetty P. Nutrition, immunity and infection. Wallingford: CABI University of
Agha R. The socio-economic implications of the coronavirus pandemic Southampton; 2010.
(COVID-19): A review. Int J Surg. 2020;78:185–93. 25. Grant WB, Lahore H, McDonnell SL, Baggerly CA. Evidence that vitamin D
7. Dubey S, Biswas P, Ghosh R, Chatterjee S, Dubey MJ, Chatterjee S, Lahiri supplementation could reduce risk of influenza and COVID-19 infections
D, Lavie CJ. Psychosocial impact of COVID-19. Diabetes Metab Syndr. and deaths. Nutrients. 2020;12(4):988.
2020;14(5):779–88. 26. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G,
8. Moreno C, Wykes T, Galderisi S, Nordentoft M, Crossley N, Jones N, Can- Brown TS, Der Nigoghossian C, Zidar DA, Haythe J, et al. Cardiovascular
non M, Correll CU, Byrne L, Carr S, et al. How mental health care should considerations for patients, health care workers, and health systems dur-
change as a consequence of the COVID-19 pandemic. Lancet Psychiatry. ing the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352–71.
2020;7(9):813–24. 27. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is
9. Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, associated with decreased mortality in severe coronavirus disease 2019
Fukuda K. Influenza-associated hospitalizations in the United States. patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094–9.
JAMA. 2004;292(11):1333–40. 28. World Health Organization. Clinical management of severe acute respira-
10. Valkenburg SA, Josephs TM, Clemens EB, Grant EJ, Nguyen TH, Wang GC, tory infection (SARI) when COVID-19 disease is suspected: interim guid-
Price DA, Miller A, Tong SY, Thomas PG, et al. Molecular basis for universal ance. Geneva: World Health Organization; 2020.
HLA-A*0201-restricted CD8+ T-cell immunity against influenza viruses. 29. Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure use-
Proc Natl Acad Sci USA. 2016;113(16):4440–5. ful in predicting risk for coronary heart disease? The Framingham Heart
11. van den Brand JM, Smits SL, Haagmans BL. Pathogenesis of Middle East Study. Circulation. 1999;100(4):354–60.
respiratory syndrome coronavirus. J Pathol. 2015;235(2):175–84. 30. Sanders E, de Wit T, Fontanet A, Goudsmit J, Miedema F, Coutinho R.
12. Louie JK, Acosta M, Samuel MC, Schechter R, Vugia DJ, Harriman K, Matyas Ethiopia-Netherlands AIDS research project. Ned Tijdschr Geneeskd.
BT. A novel risk factor for a novel virus: obesity and 2009 pandemic influ- 2001;145(26):1261.
enza A (H1N1). Clin Infect Dis . 2011;52(3):301–12.
13. Malik VS, Ravindra K. Higher body mass index is an important risk factor in
COVID-19 patients: a systematic review and meta-analysis. SSRN J. 2020.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
https://​doi.​org/​10.​2139/​ssrn.​36050​87.
lished maps and institutional affiliations.
14. Moser JS, Galindo-Fraga A, Ortiz-Hernández AA. Underweight, over-
weight, and obesity as independent risk factors for hospitalization in