Structure-function investigation of a new VUI-202012/01 SARS-CoV-2 variant (preprint)

The SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus) has accumulated multiple mutations during its global circulation. Recently, a new strain of SARS-CoV-2 (VUI 202012/01) had been identified leading to sudden spike in COVID-19 cases in South-East England. The strain has accumulated 23 mutations which have been linked to its immune evasion and higher transmission capabilities. Here, we have highlighted structural-function impact of crucial mutations occurring in spike (S), ORF8 and nucleocapsid (N) protein of SARS-CoV-2. Some of these mutations might confer higher fitness to SARS-CoV-2. SummarySince initial outbreak of COVID-19 in Wuhan city of central China, its causative agent; SARS-CoV-2 virus has claimed more than 1.7 million lives out of 77 million populations and still counting. As a result of global research efforts involving public-private-partnerships, more than 0.2 million complete genome sequences have been made available through Global Initiative on Sharing All Influenza Data (GISAID). Similar to previously characterized coronaviruses (CoVs), the positive-sense single-stranded RNA SARS-CoV-2 genome codes for ORF1ab non-structural proteins (nsp(s)) followed by ten or more structural/nsps [1, 2]. The structural proteins include crucial spike (S), nucleocapsid (N), membrane (M), and envelope (E) proteins. The S protein mediates initial contacts with human hosts while the E and M proteins function in viral assembly and budding. In recent reports on evolution of SARS-CoV-2, three lineage defining non-synonymous mutations; namely D614G in S protein (Clade G), G251V in ORF3a (Clade V) and L84S in ORF 8 (Clade S) were observed [2-4]. The latest pioneering works by Plante et al and Hou et al have shown that compared to ancestral strain, the ubiquitous D614G variant (clade G) of SARS-CoV-2 exhibits efficient replication in upper respiratory tract epithelial cells and transmission, thereby conferring higher fitness [5, 6]. As per latest WHO reports on COVID-19, a new strain referred as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) had been identified as a part of virological and epidemiological analysis, due to sudden rise in COVID-19 detected cases in South-East England [7]. Preliminary reports from UK suggested higher transmissibility (increase by 40-70%) of this strain, escalating Ro (basic reproduction number) of virus to 1.5-1.7 [7, 8]. This apparent fast spreading variant inculcates 23 mutations; 13 non-synonymous, 6 synonymous and 4 amino acid deletions [7]. In the current scenario, where immunization programs have already commenced in nations highly affected by COVID-19, advent of this new strain variant has raised concerns worldwide on its possible role in disease severity and antibody responses. The mutations also could also have significant impact on diagnostic assays owing to S gene target failures.

Determinants of Developing Symptomatic Disease in Ethiopian COVID-19 Patients: A Case-Control Study (preprint)

Background: Studies show that having some symptoms seems to be associated with more severe disease and poor prognosis. Therefore, knowing who is more susceptible to symptomatic COVID-19 disease is important to provide targeted preventive and management practice. The aim of the study was to assess the determinants of having symptomatic disease among COVID-19 patients admitted to Millennium COVID-19 Care Center in Ethiopia.Methods: A case-control study was conducted from August to September 2020 among a randomly selected 765 COVID-19 patients (372 Asymptomatic and 393 Symptomatic patients). Chi-square test and independent t-test were used to detect the presence of a statistically significant difference in the characteristics of the cases (symptomatic) and controls (asymptomatic), where p-value of <0.05 considered as having a statistically significant difference. Multivariable binary logistic regression was used to assess a statistically significant association between the independent variables and developing symptomatic COVID-19 where Adjusted Odds ratio (AOR), 95% CIs for AOR, and P-values were used for testing significance and interpretation of results. Results: The result of the multivariable binary logistic regression shows that age group (AOR= 1.818, 95% CI= 1.210, 2.731, p-value=0.004 for 30-39 years; AOR= 1.611, 95% CI= 1.016, 2.554, p-value=0.043 for 40-49 years and AOR= 4.076, 95% CI= 2.582, 6.435, p-value=0.0001 for years and above), sex (AOR= 1.672, 95% CI= 1.216, 2.299, p-value=0.002) and history of diabetes mellitus (AOR= 2.406, 95% CI= 1.384, 4.181, p-value=0.002) were found to be significant factors that determine the development of symptomatic disease in COVID-19 patients.Conclusions: Developing a symptomatic COVID-19 disease was found to be determined by exposures of old age, male sex, and being diabetic. Therefore, patients with the above factors should be given enough attention in the prevention and management process, including inpatient management, to pick symptoms earlier and to manage accordingly so that these patients can have a favorable treatment outcome. 

COVID-19 in Hospitalized Ethiopian Children: Characteristics and Outcome Profile (preprint)

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.

Characteristics and outcome profile of Hospitalized African COVID-19 patients: The Ethiopian Context (preprint)

Background: The COVID-19 pandemic seems to have a different picture in Africa; the first case was identified in the continent after it has already caused a significant loss to the rest of the world and the reported number of cases and mortality rate has been low. Understanding the characteristics and outcome of the pandemicin the African setup is therefore crucial. Aim: To assess the characteristics and outcome of COVID-19 patients and to identify determinants of the disease outcome among patients admitted to Millennium COVID-19 Care Center in Ethiopia. Methods: A prospective cohort study was conducted among 1345 consecutively admitted RT-PCR confirmed COVID-19 patients from July to 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. Cox proportional hazard survival model was used to identify determinants of time to clinical improvement and the independent variables, where adjusted hazard ratio, P-value and 95% CI for adjusted hazard ratio were used for testing significance and interpretation of results. Binary logistic regression model was used to assess the presence of a statistically significant association between disease outcome and the independent variables, where adjusted odds ratio, P-value and 95% CI for adjusted odds ratio were used for testing significance and interpretation of results Results: Among the study population, 71 (5.3%) died, 72 (5.4%) were transferred and the rest 1202 (89.4%) were clinically improved. The median time to clinical improvement was 14 days. On the multivariable Cox proportional hazard model; temperature (AHR= 1.135, 95% CI= 1.011, 1.274, p-value=0.032), COVID-19 severity (AHR= 0.660, 95% CI= 0.501, 0.869, p-value=0.003), and cough (AHR= 0.705, 95% CI= 0.519, 0.959, p-value=0.026) were found to be significant determinants of time to clinical improvement. On the binary logistic regression, the following factors were found to be significantly associated with disease outcome; SPO2 (AOR= 0.302, 95% CI= 0.193, 0.474, p-value=0.0001), shortness of breath (AOR= 0.354, 95% CI= 0.213, 0.590, p-value=0.0001) and diabetes mellitus (AOR= 0.549, 95% CI= 0.337, 0.894, p-value=0.016). Conclusions: The average duration of time to clinical improvement was 14 days and 89.4 % of the patients achieved clinical improvement. The mortality rate of the studied population is lower than reports from other countries including those in Africa. Having severe COVID-19 disease severity and presenting with cough were found to be associated with delayed clinical improvement ofthe disease. On the other hand, being hyperthermic is associated with shorter disease duration (faster time to clinical improvement). In addition, lower oxygen saturation and subjective complaint of shortness of breath and being diabetic were associated with unfavorable disease outcome. Therefore, patients with these factors should be followed cautiously for a better outcome.

Duration of Oxygen Requirement and Predictors in Severe COVID-19 Patients in Ethiopia: A Survival Analysis (preprint)

Aim: To estimate time to getting off supplemental oxygen therapy and identify predictors among COVID-19 patients admitted to Millennium COVID-19 Care Center in Addis Ababa, Ethiopia. Methods: A prospective observational study was conducted among 244 consecutively admitted COVID-19 patients from July to 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. Cox proportional hazard survival model was used to assess the presence of a statistically significant association between time to getting off supplemental oxygen therapy and the independent variables, where hazard ratio, P-value and 95% CI for hazard ratio were used for testing significance and interpretation of results. Results: Median time to getting off supplemental oxygen therapy among the studied population was 6 days. Factors that affect time to getting off supplemental oxygen therapy were age group (HR= 0.522, 95% CI= 0.323, 0.844, p-value=0.008 for [≥] 70 years) and shortness of breath (HR= 0.705, 95% CI= 0.519, 0.959, p-value=0.026). Conclusions: Average duration of supplemental oxygen therapy requirement among COVID-19 patients was 6 days and being 70 years and older and having shortness of breath were found to be associated with prolonged duration of supplemental oxygen therapy requirement. This result can be used as a guide in planning institutional resource allocation and patient management to provide a well equipped care to prevent complications and death from the disease.

Determinants of Developing Symptomatic Disease in Ethiopian COVID-19 Patients (preprint)

Background: Studies show that having some symptoms seems to be associated with more severe disease and poor prognosis. Therefore, knowing who is more susceptible to symptomatic COVID-19 disease is important to provide targeted preventive and management practice. The aim of the study was to assess the determinants of having symptomatic disease among COVID-19 patients admitted to Millennium COVID-19 Care Center in Ethiopia. Methods: A case-control study was conducted from August to September 2020 among a randomly selected 765 COVID-19 patients (372 Asymptomatic and 393 Symptomatic patients). Chi-square test and independent t-test were used to detect the presence of a statistically significant difference in the characteristics of the cases (symptomatic) and controls (asymptomatic), where p-value of <0.05 considered as having a statistically significant difference. Multivariable binary logistic regression was used to assess a statistically significant association between the independent variables and developing symptomatic COVID-19 where Adjusted Odds ratio (AOR), 95% CIs for AOR, and P-values were used for testing significance and interpretation of results. Results: The result of the multivariable binary logistic regression shows that age group (AOR= 1.818, 95% CI= 1.210, 2.731, p-value=0.004 for 30-39 years; AOR= 1.611, 95% CI= 1.016, 2.554, p-value=0.043 for 40-49 years and AOR= 4.076, 95% CI= 2.582, 6.435, p-value=0.0001 for years and above), sex (AOR= 1.672, 95% CI= 1.216, 2.299, p-value=0.002) and history of diabetes mellitus (AOR= 2.406, 95% CI= 1.384, 4.181, p-value=0.002) were found to be significant factors that determine the development of symptomatic disease in COVID-19 patients. Conclusions: Developing a symptomatic COVID-19 disease was found to be determined by exposures of old age, male sex, and being diabetic. Therefore, patients with the above factors should be given enough attention in the prevention and management process, including inpatient management, to pick symptoms earlier and to manage accordingly so that these patients can have a favorable treatment outcome.