key: cord-329499-jh4pbqxu
authors: Leulseged, T. W.; Hassen, I. S.; Maru, E. H.; Zewde, W. C.; Chamiso, N. W.; Edo, M. G.; Abebe, D. S.; Aliy, M. A.
title: COVID-19 in Hospitalized Ethiopian Children: Characteristics and Outcome Profile
date: 2020-11-04
journal: nan
DOI: 10.1101/2020.10.30.20223115
sha: 
doc_id: 329499
cord_uid: jh4pbqxu

Background: Considering the number of people affected and the burden to the health care system due to the Coronavirus pandemic, there is still a gap in understanding the disease better leaving a space for new evidence to be filled by researchers. This scarcity of evidence is observed especially among children with the virus. Understanding the disease pattern and its effect among children is vital in providing timely and targeted intervention. Aim: To assess the characteristics and outcome profile of 115 RT-PCR confirmed children with COVID-19, and to determine the presence of significant difference in disease severity and survival distribution between groups among children admitted to Millennium COVID-19 Care Center in Ethiopia. Methods: A prospective cohort study was conducted among 90 consecutively admitted eligible RT-PCR confirmed COVID-19 children from end of June to mid September, 2020. Frequency tables, KM plots, median survival times and Log-rank test were used to describe the data and compare survival distribution between groups. A chi-square test/ Fischer exact test were used to determine the presence of a significant difference between the independent variables and disease severity. A statistically significant difference was detected for variables with a P-value of [≤] 0.05. Survival experience of different groups was compared using KM survival curves. Log-rank test was used to assess the presence of significant difference among survival distributions of groups for equality where a statistically significant difference in survival distribution between groups was detected for variables with a P-value of [≤] 0.05. Results: From the 90 children, 67 (74.4%) achieved clinical improvement and 23 (25.6%) were censored. There was no death. The median time to clinical improvement was 14 days. The median age of the participants was 15 years and 63.3% of the participants were females. The commonest reported route of disease transmission was through close contact with a diagnosed person (45.6%). Only three (3.3%) had a history of pre-existing comorbid illness. More than a quarter (26.7%) had one or more symptoms at admission, the commonest being cough (22.2%). Seventy three (81.1%) of the patients had mild COVID-19 at admission and the rest (18.9%) had moderate disease. On the chi-square and Fischers exact test, children with one or more symptom at presentation (73.3% Vs 36.7%, p-value= 0.0001), fever (40.0 % Vs 60.0%, p-value=0.045), cough (20.0 % Vs 80.0%, p-value=0.0001), sore throat (44.4 % Vs 55.6%, p-value=0.011), and headache (44.4 % Vs 55.6%, p-value=0.011) were more likely to develop moderate COVID-19. On the log rank test, a significant difference in survival between groups was observed only for sex. A significantly longer time was needed for female patients to achieve clinical improvement compared to male patients (15 days Vs 14 days, p-value= 0.042). Conclusions: The average duration of time to clinical improvement was 14 days and 74.4% achieved clinical improvement. There was no death during the observation period. The pediatric patients seemed to have a milder disease presentation and a favorable outcome compared to other countries report and also the adult pattern observed in our country. Having particular symptom groups is associated with the development of moderate COVID-19. Being female seemed to delay the time to clinical improvement. Further multicenter study with a large sample size is recommended to reach at a better conclusion.

The Corona Virus pandemic which affected more than 43, 341, 451 individuals and resulted in 93,707 deaths worldwide, as of October 27 2020, is reported to affect all age groups 1 . Age classified report of the disease in terms of incidence, severity and outcome showed that younger age groups have far less probability of acquiring the disease and with milder disease course and favorable outcome if they do get infected 2 .

Studies conducted till now have focused mainly on adult patients, resulting in less understating of the disease presentation and outcome among children especially in the African set up. To date there is no study conducted in Africa.

According to studies conducted till today, the disease seemed to be common among males just like the report from adults 3, 4 . The commonly affected age groups are in the two extremes, infants and adolescent 3, 5 . The majority of kids are reported to acquire the disease through household contact with adults 6, 7 .

Both symptomatic and asymptomatic cases are reported, with a number of studies showing that a higher proportion of children had one or more symptom at presentation. The commonly reported symptoms are fever and cough, with fever being the predominant symptom in many countries. Non specific symptoms like fatigue and myalgia are also reported [6] [7] [8] [9] . This is unlike the adult reports where respiratory symptoms were recorded to be the commonest [10] [11] [12] [13] [14] [15] [16] .

Mild and moderate diseases are commonly reported with severe and critical cases observed in relatively few cases 6, 8, 9 . Admission to critical care was determined by age and race 3 . Underlying comorbid illness was found in a considerable proportion of hospitalized patients ranging from 42% in one study to 83% in another study 3, 4 .

Laboratory derangements including lymphopenia, leucopenia, increased D-dimer and increased Creatinine are reported as common findings. Chest x-ray reports of children with pneumonia showed that more than half had a ground glass opacity pattern 8,9 . Possible outcomes reported range from a complete uneventful recovery to complications like multiple organ failure and multiple inflammatory syndrome up to death. A more favorable disease outcome is observed among children compared to adults with few reports of complications and mortality rate of 1-4% 3-6 .

Due to lack of study among Children with COVID-19 in Africa, understanding the disease pattern and its outcome is mandatory to guide decision making. Therefore, in this study we aimed to assess the characteristics and outcome profile of 115 RT-PCR confirmed children with COVID-19, and to determine the presence of significant difference in disease severity and survival distribution between groups among children admitted to Millennium COVID-19 Care Center in Ethiopia.

An institution based prospective cohort study design was conducted at Millennium COVID-19 Care Center (MCCC), a makeshift hospital in Addis Ababa, Ethiopia. The follow up was made from end of June to mid September, 2020.

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The source population was all consecutively admitted children with COVID-19 admitted to MCCC with a confirmed diagnosis of COVID-19 using RT-PCR, as reported by a laboratory given mandate to test such patients by the Ethiopian Federal Ministry of Health and who were on follow up from end of June to mid September, 2020 17 .

All consecutively admitted children with COVID-19 during the three months follow up period were included in the study. During this interval a total of 115 COVID-19 patients were admitted to the Center.

All children with COVID-19 who were on treatment and follow up at the center from end of June to mid September, 2020 and with complete follow up data were included o Hypoxia: SPO2 ≤ 93% on atmospheric air or PaO2:FiO2 < 300mmHg (SF ratio < 315) o Tachypnea: in respiratory distress or RR>30 breaths/minutes o More than 50% involvement seen on chest imaging Event: Achieving clinical improvement from COVID-19.

Censoring: Represents patients lost to follow-up, transferred out, died or completed the followup period before achieving clinical improvement. Time to event or censoring: Time between admission to the Center up to clinical improvement/ censoring (in days).

A pre-tested interviewer administered questionnaire was used to collect data from patients and their medical charts. The data was collected by trained data collectors and all the necessary . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020. 10.30.20223115 doi: medRxiv preprint precautions in order to prevent the acquisition and disseminate the virus were taken during the data collection process. Before coding and analysis the data, data consistency and completeness was checked and necessary measures were taken.

The collected data was coded and entered into Epi-Info version 7.2.1.0, cleaned and stored and exported into SPSS version 23 for analysis. Data was summarized using frequency tables, Kaplan Meier (KM) plots and median survival times.

A chi-square test (or Fischer's exact test for those variables which do not meet the chi-square assumptions) were used to determine the presence of a significant difference between the underlying characteristics of the children and COVID-19 disease severity. A statistically significant difference was detected for variables with a P-value of ≤ 0.05.

Survival experience of different groups was compared using KM survival curves. Log-rank test was used to assess the presence of significant difference among survival distributions of groups for equality. A statistically significant difference in survival distribution between groups was detected for variables with a P-value of ≤ 0.05.

From the 115 children admitted during the study period, information was collected from 90 children with complete medical recording. Among the 90 patients, 67 (74.4%) achieved clinical improvement and 23 (25.6%) were censored. All of the censored observations happened because of transfer to another hospital. The median time to clinical improvement was 14 days.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020.10.30.20223115 doi: medRxiv preprint 

The median age of the participants weas 15 years and it ranges from 6 month up to 18 years. The majority (36.7%) of the participants were 15 to 18 years. Almost two third (63.3%) of the participants were females. The majority (88.9%) were from Addis Ababa, the capital city of Ethiopia. The commonest reported route of disease transmission was through close contact with a diagnosed person (45.6%).

Only three (3.3%) had a history of pre-existing comorbid illness, two had bronchial asthma and one had a history of valvular heart disease. More than a quarter (26.7%) of the patients had one or more symptom at admission. The commonest symptom was cough (22.2%), followed by sore throat and headache (each constitutes 10%), fever, runny nose, chest pain and fatigue (each constitutes 5.6%) and then nausea and vomiting (4.4%).

Seventy three (81.1%) of the patients had mild COVID-19 at admission and the rest (18.9%) had moderate disease.

Based on the chi-square/ Fischer's exact test result, a significant difference in COVID-19 disease severity was observed among the groups classified by the presence of symptom, fever, cough, sore throat, chest pain and headache. Accordingly, children with moderate COVID-19 were more . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 4, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020.10.30.20223115 doi: medRxiv preprint

The mean (± standard deviation) vital sign values of the studied population was as follows; heart rate of 94.7 beats/ min (± 15.7), respiratory rate of 19.8 breath/min (± 2.9), systolic blood pressure of 126.0 mmHg (± 14.4), diastolic blood pressure of 74.4 mmHg (± 8.8), temperature of 36.4 o C (± 0.81) and oxygen saturation of 96.1% (± 1.7).

Based on the results of the independent t-test, a significant difference in baseline vital sign values between mid and moderate cases was observed only in the respiratory rate value ( 

The complete blood count result of the 17 moderate COVID-19 patients showed that the mean hemoglobin, hematocrit, white blood cell and platelet counts were 14.96 mg/dl (± 1.82), 41.65 % (± 9.92), 6.87 x10 3 /L (± 2.33) and 282.0 x10 3 /L (± 82.37) respectively.

The renal function test showed that; the mean (± SD) value of urea and creatinine were 27.82 mg/dl (± 9.88) and 0.65 mg/dl (± 0.25).

The liver function laboratory report revealed that the mean (± SD) values of ALT, AST and ALP were 20.67 IU/L (± 0.99), 21.82 IU/L (± 8.61) and 109.69 IU/L (± 68.07) respectively. ( Table 3 ) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 4, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 4, 2020. Similarly, the KM survival function graph showed that males have a favorable survival experience (time to clinical improvement) compared to females. The KM hazard function also showed that the instantaneous chance of achieving recovery increases for both sexes as the duration of illness increases, with a more favorable pattern seen for males. (Figure 2) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020.10.30.20223115 doi: medRxiv preprint 

To date there is no research on COVID-19 infected children in Africa. Therefore, in this study we have assessed the characteristics and outcome profile of 90 RT-PCR confirmed children with COVID-19 who were admitted to Millennium COVID-19 Care Center in Ethiopia from end of June to mid September, 2020. Understanding this will guide the existing practice. Among the study population 74.4% achieved clinical improvement and the median time to clinical improvement was 14 days. Similarly, a study conducted in China among pediatric patients showed that the median time to cure was 16 days 6 . The median time to recovery among adults was also the same in the study area 18 .

In the current study, there was no death among the study population. This is in contrast to a study conducted in United Kingdom and North America where mortality rate of 1% and 4% were reported, respectively 4 . This also shows that the disease might have a different pattern compared to adults as a study conducted at our Center among adults reported a mortality rate of 5.3% 18 . This difference could be attributed to the small sample size in our study.

The median age of the participants was 15 years and it ranges from 6 month up to 18 years. A similar finding was observed in the North American study 4 . Two third of the participants were 11 to 18 years of age. This age group was also reported to have a higher disease incidence than the younger groups in a pattern that is recorded in the United States 5 .

Almost two third (63.3%) of the participants were females unlike the pediatric studies conducted in other countries where the majority of infected children are males 3, 4 . In addition, researches . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020.10.30.20223115 doi: medRxiv preprint conducted among adults in our center also showed a contrasting pattern where the majority of infected are males [18] [19] [20] [21] [22] [23] .

Close contact with a diagnosed person constituted the major (45.6%) route of disease transmission. This was found to be the case in other studies as well where 66% up to 95.6% of admitted children were reported to acquired the disease through household contact with adults 6, 7 . This shows that there is a potential for an increase in the number of new infection among children since both globally and nationally the number of new cases among adults is increasing at an alarming rate from day to day implying the need for taking effective precautions among adults in order to protect the children.

Only three (3.3%) had a history of pre-existing comorbid illness, two had bronchial asthma and one had a history of valvular heart disease. This seems to be in contrast to other studies where 42% up to 83% of admitted children had a history of one or more pre-existing co-morbid illness 3, 4 .

The majority (73.3%) of the participants were asymptomatic at presentation. On the other hand, other studies reported 73% up to 94.1 % of children presenting with one or more symptom 4, 6, 8 . The commonest symptom was cough (22.2%), followed by sore throat and headache (each constitute 10%), fever, runny nose, chest pain and fatigue (each constitute 5.6%) and then nausea and vomiting (4.4%). Cough was also reported to be the major presentation in another study in China 7 but fever was found to be the commonest presenting symptom in a number of studies including systematic review and meta-analysis studies that included more than 120 articles 6,8,9 . Seventy three (81.1%) of the patients had mild COVID-19 at admission and the rest (18.9%) had moderate disease. There was no severe or critical case. On the contrary, studies from other countries revealed that a considerable proportion of children was diagnosed with severe and critical illness with a need of Intensive care unit admission and invasive ventilation [3] [4] [5] [6] 8 .

Based on the chi-square/ Fischer's exact test result, the chance of developing moderate disease increases for those with one or more symptom at presentation, particularly those with fever, cough, sore throat, and headache. This indicates that in addition to the symptom categories listed as diagnostic criteria for moderate disease, the symptoms listed here might have a more predictive value in disease classification towards a more severe category than what is thought till now.

According to the log rank test and KM survival and hazard graphs, a significant difference in survival between groups was observed only for sex. A significantly longer time was needed for female patients to achieve clinical improvement compared to male patients. Otherwise, the time to clinical improvement didn't show significant difference among the groups classified by age group, symptoms and disease severity. This is an opposing pattern compared to adult findings in . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020.10.30.20223115 doi: medRxiv preprint the center where survival distribution showed a significant difference between groups classified by age, symptom and disease severity but didn't show a difference between the two sexes 18 .

The average duration of time to clinical improvement was 14 days and 74.4% achieved clinical improvement. There was no death during the observation period. The pediatric patients seemed to have a milder disease presentation and favorable outcome compared to other countries report and also the adult pattern observed in our country.

Having one or symptom particularly fever, cough, sore throat, and headache are associated with development of moderate COVID-19. A less favorable survival experience (delayed time to clinical improvement) was observed for females compared with males.

Further multicenter study with a large sample size is recommended to reach at a better conclusion.

The study was conducted after obtaining ethical clearance from St. Paul's Hospital Millennium Medical College Institutional Review Board. Written informed consent was obtained from the participants and/or their care givers. The study had no risk/negative consequence on those who participated in the study. Medical record numbers were used for data collection and personal identifiers were not used in the research report. Access to the collected information was limited to the principal investigator and confidentiality was maintained throughout the project.

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The authors would like to thank St. Paul's Hospital Millennium Medical College for facilitating the research work.

The authors declare that they have no known competing interests Funding source: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Authors Contribution: TWL conceived and designed the study, revised data extraction sheet, performed statistical analysis, and drafted the initial manuscript. All authors contributed to the conception of the study and obtained patient data. All authors undertook review and interpretation of the data. All authors revised the manuscript and approved the final version.