SARS-CoV-2 seroprevalence and implications for population immunity: Evidence from two Health and Demographic Surveillance System sites in Kenya, February-June 2022 (preprint)

Background Up-to-date SARS-CoV-2 antibody seroprevalence estimates are important for informing public health planning, including priorities for Coronavirus disease 2019 (COVID-19) vaccination programs. We sought to estimate infection- and vaccination-induced SARS-CoV-2 antibody seroprevalence within representative samples of the Kenyan population approximately two years into the COVID-19 pandemic and approximately one year after rollout of the national COVID-19 vaccination program. Methods We conducted cross-sectional serosurveys within random, age-stratified samples of Kilifi Health and Demographic Surveillance System (HDSS) and Nairobi Urban HDSS residents. Anti-spike (anti-S) immunoglobulin G (IgG) and anti-nucleoprotein (anti-N) IgG were measured using validated in-house ELISAs. Target-specific Bayesian population-weighted seroprevalence was calculated overall, by sex and by age, with adjustment for test performance as appropriate. Anti-S IgG concentrations were estimated with reference to the WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin and their reverse cumulative distributions plotted. Results Between February and June 2022, 852 and 851 individuals within the Kilifi HDSS and the Nairobi Urban HDSS, respectively, were sampled. Only 11.0% (95% confidence interval [CI] 9.0-13.3) of all Kilifi HDSS participants and 33.4% (95%CI 30.2-36.6) of all Nairobi Urban HDSS participants had received any doses of COVID-19 vaccine. Population-weighted anti-S IgG seroprevalence was 69.1% (95% credible interval [CrI] 65.8-72.3) within the Kilifi HDSS and 88.5% (95%CrI 86.1-90.6) within the Nairobi Urban HDSS. Among COVID-unvaccinated residents of the Kilifi HDSS and Nairobi Urban HDSS, it was 66.7% (95%CrI 63.3-70.0) and 85.3% (95%CrI 82.1-88.2), respectively. Population-weighted, test-adjusted anti-N IgG seroprevalence within the Kilifi HDSS was 53.5% (95%CrI 46.5-61.1) and 65.5% (95%CrI 56.0-75.6) within the Nairobi Urban HDSS. The prevalence of anti-N antibodies was similar in vaccinated and unvaccinated subgroups in both HDSS populations. Anti-S IgG concentrations were significantly lower among Kilifi HDSS residents than among Nairobi Urban HDSS residents (p< 0.001). Conclusions Approximately, 7 in 10 Kilifi residents and 9 in 10 Nairobi residents were seropositive for anti-S IgG by May 2022 and June 2022, respectively. Given COVID-19 vaccination coverage, anti-S IgG seropositivity among COVID-unvaccinated individuals, and anti-N IgG seroprevalence, population-level anti-S IgG seroprevalence was predominantly derived from infection. Interventions to improve COVID-19 vaccination uptake should be targeted to individuals in rural Kenya who are at high risk of severe COVID-19.

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.

Revealing the extent of the COVID-19 pandemic in Kenya based on serological and PCR-test data (preprint)

Policy makers in Africa need robust estimates of the current and future spread of SARS-CoV-2. Data suitable for this purpose are scant. We used national surveillance PCR test, serological survey and mobility data to develop and fit a county-specific transmission model for Kenya. We estimate that the SARS-CoV-2 pandemic peaked before the end of July 2020 in the major urban counties, with 34 - 41% of residents infected, and will peak elsewhere in the country within 2-3 months. Despite this penetration, reported severe cases and deaths are low. Our analysis suggests the COVID-19 disease burden in Kenya may be far less than initially feared. A similar scenario across sub-Saharan Africa would have implications for balancing the consequences of restrictions with those of COVID-19.

The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya (preprint)

BackgroundThe COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region. MethodsCombining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020. FindingsIn February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 22% (0-46). As the COVID-19 restrictions to physical contact are lifted, from December 2020, the probability of a large measles outbreak increased to 31% (8-51), 35% (16-52) and 43% (31-56) assuming a 15%, 50% and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 37% (17-54), 44% (29-57) and 57% (48-65) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of restrictions on contact can be overcome by conducting an SIA with [≥] 95% coverage in under-fives. InterpretationWhile contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once physical distancing is relaxed. Implementing delayed SIAs will be critical for prevention of measles outbreaks once contact restrictions are fully lifted in Kenya. FundingThe United Kingdoms Medical Research Council and the Department for International Development

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.