Genomic epidemiology of SARS-CoV-2 within households in coastal Kenya: a case ascertained cohort study (preprint)

Background Analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequence data from household infections should aid its detailed epidemiological understanding. Using viral genomic sequence data, we investigated household SARS-CoV-2 transmission and evolution in coastal Kenya households. Methods We conducted a case-ascertained cohort study between December 2020 and February 2022 whereby 573 members of 158 households were prospectively monitored for SARS-CoV-2 infection. Households were invited to participate if a member tested SARS-CoV-2 positive or was a contact of a confirmed case. Follow-up visits collected a nasopharyngeal/oropharyngeal (NP/OP) swab on days 1, 4 and 7 for RT-PCR diagnosis. If any of these were positive, further swabs were collected on days 10, 14, 21 and 28. Positive samples with an RT-PCR cycle threshold of <33.0 were subjected to whole genome sequencing followed by phylogenetic analysis. Ancestral state reconstruction was used to determine if multiple viruses had entered households. Results Of 2,091 NP/OP swabs that were collected, 375 (17.9%) tested SARS-CoV-2 positive. Viral genome sequences (>80% coverage) were obtained from 208 (55%) positive samples obtained from 61 study households. These genomes fell within 11 Pango lineages and four variants of concern (Alpha, Beta, Delta and Omicron). We estimated 163 putative transmission events involving members of the sequenced households, 40 (25%) of which were intra-household transmission events while 123 (75%) were infections that likely occurred outside the households. Multiple virus introductions (up-to-5) were observed in 28 (47%) households with the 1-month follow-up period. Conclusions We show that a considerable proportion of SARS-CoV-2 infections in coastal Kenya occurred outside the household setting. Multiple virus introductions frequently occurred into households within the same infection wave in contrast to observations from high income settings, where single introduction appears to be the norm. Our findings suggests that control of SARS-CoV-2 transmission by household member isolation may be impractical in this setting.

SARS-CoV-2 Seroprevalence in three Kenyan Health and Demographic Surveillance Sites, December 2020-May 2021 (preprint)

Importance Most of the studies that have informed the public health response to the COVID-19 pandemic in Kenya have relied on samples that are not representative of the general population. Objective To determine the cumulative incidence of infection with SARS-CoV-2, from a randomly selected sample of individuals normally resident at three Health and Demographic Surveillance Systems (HDSSs) in Kenya. Design This was a cross-sectional population-based serosurvey conducted at Kilifi HDSS, Nairobi Urban HDSS, and Manyatta HDSS in Kenya. We selected age-stratified samples at HDSSs in Kilifi, Kisumu and Nairobi, in Kenya. Blood samples were collected from participants between 01 Dec 2020 and 27 May 2021. Setting Kilifi HDSS comprises a predominantly rural population, Manyatta HDSS comprises a predominantly semi-urban population, while Nairobi Urban HDSS comprises an urban population. The total population under regular surveillance at the three sites is ~470,000. Exposure We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Locally validated assay sensitivity and specificity were 93% (95% CI 88-96%) and 99% (95% CI 98-99.5%), respectively. Main Outcome and Measures The primary outcome measure was cumulative incidence of infection with SARS-COV-2 virus as evidenced by seropositivity to SARS-CoV-2 whole spike protein. We adjusted our estimates using classical methods and Bayesian modelling to account for assay performance. We performed multivariable logistic regression to test associations between seropositivity and age category, time period and sex. Results We recruited 2,559 individuals from the three HDSS sites, median age (IQR) 27years (10-78) and 52% were female. Seroprevalence at all three sites rose steadily during the study period. In Kilifi, Kisumu and Nairobi, seroprevalences at the beginning of the study were 14.5 % (9.1-21), 36.0 (28.2-44.4) and 32.4 % (23.1-42.4) respectively; at the end they were 27.6 % (21.4-33.9), 42.0 % (34.7-50.0) and 50.2 % (39.7-61.1), respectively. In multivariable logistic regression models that adjusted for sex and period of sample collections, age category was strongly associated with seroprevalence (p<0.001), with the highest seroprevalences being observed in the 35-44 and [≥]65 year age categories. Conclusion There has been substantial unobserved transmission of SARS-CoV-2 in the general population in Kenya. There is wide variation in cumulative incidence by location and age category.

Social mixing patterns relevant to infectious diseases spread by close contact in urban Blantyre, Malawi. (preprint)

Introduction: Understanding human mixing patterns relevant to infectious diseases spread through close contact is vital for modelling transmission dynamics and optimisation of disease control strategies. Mixing patterns in low-income countries like Malawi are not well understood. Methodology: We conducted a social mixing survey in urban Blantyre, Malawi between April and July 2021 (between the 2nd and 3rd wave of COVID-19 infections). Participants living in densely-populated neighbourhoods were randomly sampled and, if they consented, reported their physical and non-physical contacts within and outside homes lasting at least 5 minutes during the previous day. Age-specific mixing rates were calculated, and a negative binomial mixed effects model was used to estimate determinants of contact behaviour. Results: Of 1,201 individuals enrolled, 702 (58.5%) were female, the median age was 15 years (interquartile range [IQR] 5-32) and 127 (10.6%) were HIV-positive. On average, participants reported 10.3 contacts per day (range: 1-25). Mixing patterns were highly age-assortative, particularly those within the community and with skin-to-skin contact. Adults aged 20-49y reported the most contacts (median:11, IQR: 8-15) of all age groups; 38% (95%CI: 16-63) more than infants (median: 8, IQR: 5-10), who had the least contacts. Household contact frequency increased by 3% (95%CI 2-5) per additional household member. Unemployed participants had 15% (95%CI: 9-21) fewer contacts than other adults. Among long range (>30 meters away from home) contacts, secondary school children had the largest median contact distance from home (257m, IQR 78-761). HIV-positive status in adults >18 years-old was not associated with increased contact patterns (1%, 95%CI -9-12). During this period of relatively low COVID-19 incidence in Malawi, 301 (25.1%) individuals stated that they had limited their contact with others due to COVID-19 precautions; however, their reported contacts were not fewer (8%, 95%CI 1-13). Conclusion: In urban Malawi, contact rates, are high and age-assortative, with little behavioural change due to either HIV-status or COVID-19 circulation. This highlights the limits of contact-restriction-based mitigation strategies in such settings and the need for pandemic preparedness to better understand how contact reductions can be enabled and motivated. Keywords: Social contacts, Transmission, Mixing data, Infectious disease, Malawi, Africa

COVID-19 and Technology Enhanced Teaching in Higher Education in Sub-Saharan Africa: A Case of the University of Dar es Salaam, Tanzania

This article aims to share an experience on the process taken by the University of Dar es Salaam to adopt and deliver technology-enhanced teaching and learning during the COVID-19 crisis. The university started by forming a team which conducted an audit to identify existing ICT infrastructure, skills gaps amongst instructors, and information systems that could be quickly adopted to deliver various courses during the COVID-19 crisis. The Moodle system, Zoom video conferencing system, and Postgraduate Information Management System were identified and recommended. After the audit, 340 instructors were trained on identified systems and 369 new courses were developed. Although face-to-face classes resumed a few months after the training and preparations, postgraduate courses continued to be offered via the blended mode with the Zoom and Moodle systems being used. The experience gathered from this study contributes towards knowledge of ICT integration in teaching and learning and can be integrated into teaching during the COVID-19 crisis in resource-constrained universities in sub-Saharan Africa and beyond.

Prevalence of SARS-CoV-2 Antibodies from a one-year National Serosurveillance of Kenyan Blood Transfusion Donors (preprint)

In tropical Africa, SARS-CoV-2 epidemiology is poorly described because of lack of access to testing and weak surveillance systems. Since April 2020, we followed SARS-CoV-2 seroprevalence in plasma samples across the Kenya National Blood Transfusion Service. We developed an IgG ELISA against full length spike protein. Validated in locally-observed, PCR-positive COVID-19 cases and in pre-pandemic sera, sensitivity was 92.7% and sensitivity was 99.0%. Using sera from 9,922 donors, we estimated national seroprevalence of SARS-CoV-2 antibodies at 4.3% in April-June 2020 and 9.1% in August-September 2020. The second COVID-19 wave peaked in November 2020. Here we estimate national seroprevalence in early 2021. Between January 3 and March 15, 2021, we collected 3,062 samples from donors aged 16-64 years. Among 3,018 samples that met our study criteria 1,333 were seropositive (crude seroprevalence 44.2%, 95% CI 42.4-46.0%). After Bayesian test-performance adjustment and population weighting to represent the national population distribution, the national estimate of seroprevalence was 48.5% (95% CI 45.2-52.1%). Seroprevalence varied little by age or sex but was higher in Nairobi, the capital city, and lower in two rural regions. Almost half of Kenyan adult donors had evidence of past SARS-CoV-2 infection by March 2021. Although high, the estimate is corroborated by other population-specific estimates in country. Between March and June, 2% of the population were vaccinated against COVID-19 and the country experienced a third epidemic wave. Natural infection is outpacing vaccine delivery substantially in Africa, and this reality needs to be considered as objectives of the vaccine programme are set.

Improving SARS-CoV-2 cumulative incidence estimation through mixture modelling of antibody levels (preprint)

As countries decide on vaccination strategies and how to ease movement restrictions, estimates of cumulative incidence of SARS-CoV-2 infection are essential in quantifying the extent to which populations remain susceptible to COVID-19. Cumulative incidence is usually estimated from seroprevalence data, where seropositives are defined by an arbitrary threshold antibody level, and adjusted for sensitivity and specificity at that threshold. This does not account for antibody waning nor for lower antibody levels in asymptomatic or mildly symptomatic cases. Mixture modelling can estimate cumulative incidence from antibody-level distributions without requiring adjustment for sensitivity and specificity. To illustrate the bias in standard threshold-based seroprevalence estimates, we compared both approaches using data from several Kenyan serosurveys. Compared to the mixture model estimate, threshold analysis underestimated cumulative incidence by 31% (IQR: 11 to 41) on average. Until more discriminating assays are available, mixture modelling offers an approach to reduce bias in estimates of cumulative incidence.

Seroprevalence of Antibodies to SARS-CoV-2 among Health Care Workers in Kenya (preprint)

BackgroundFew studies have assessed the seroprevalence of antibodies against SARS-CoV-2 among Health Care Workers (HCWs) in Africa. We report findings from a survey among HCWs in three counties in Kenya. MethodsWe recruited 684 HCWs from Kilifi (rural), Busia (rural) and Nairobi (urban) counties. The serosurvey was conducted between 30th July 2020 and 4th December 2020. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Assay sensitivity and specificity were 93% (95% CI 88-96%) and 99% (95% CI 98-99.5%), respectively. We adjusted prevalence estimates using Bayesian modeling to account for assay performance. ResultsCrude overall seroprevalence was 19.7% (135/684). After adjustment for assay performance seroprevalence was 20.8% (95% CI 17.5-24.4%). Seroprevalence varied significantly (p<0.001) by site: 43.8% (CI 35.8-52.2%) in Nairobi, 12.6% (CI 8.8-17.1%) in Busia and 11.5% (CI 7.2-17.6%) in Kilifi. In a multivariable model controlling for age, sex and site, professional cadre was not associated with differences in seroprevalence. ConclusionThese initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies among truck drivers and assistants in Kenya (preprint)

In October 2020, anti-SARS-CoV-2 IgG seroprevalence among truck drivers and their assistants (TDA) in Kenya was 42.3%, higher than among other key populations. TDA transport essential supplies during the COVID-19 pandemic, placing them at increased risk of being infected and of transmitting SARS-CoV-2 infection over a wide geographical area.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Kenyan blood donors (preprint)

BackgroundThere are no data on SARS-CoV-2 seroprevalence in Africa though the COVID-19 epidemic curve and reported mortality differ from patterns seen elsewhere. We estimated the anti-SARS-CoV-2 antibody prevalence among blood donors in Kenya. MethodsWe measured anti-SARS-CoV-2 spike IgG prevalence by ELISA on residual blood donor samples obtained between April 30 and June 16, 2020. Assay sensitivity and specificity were 83% (95% CI 59-96%) and 99.0% (95% CI 98.1-99.5%), respectively. National seroprevalence was estimated using Bayesian multilevel regression and post-stratification to account for non-random sampling with respect to age, sex and region, adjusted for assay performance. ResultsComplete data were available for 3098 of 3174 donors, aged 15-64 years. By comparison with the Kenyan population, the sample over- represented males (82% versus 49%), adults aged 25-34 years (40% versus 27%) and residents of coastal Counties (49% versus 9%). Crude overall seroprevalence was 5.6% (174/3098). Population-weighted, test- adjusted national seroprevalence was 5.2% (95% CI 3.7- 7.1%). Seroprevalence was highest in the 3 largest urban Counties - Mombasa (9.3% [95% CI 6.4-13.2%)], Nairobi (8.5% [95% CI 4.9-13.5%]) and Kisumu (6.5% [95% CI 3.3-11.2%]). ConclusionsWe estimate that 1 in 20 adults in Kenya had SARS-CoV-2 antibodies during the study period. By the median date of our survey, only 2093 COVID-19 cases and 71 deaths had been reported through the national screening system. This contrasts, by several orders of magnitude, with the numbers of cases and deaths reported in parts of Europe and America when seroprevalence was similar.