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

BackgroundUp-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. MethodsWe 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. ResultsBetween 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). ConclusionsApproximately, 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.

Epidemiological impact and cost-effectiveness analysis of COVID-19 vaccination in Kenya

BackgroundFew studies have assessed the benefits of COVID-19 vaccines in settings where most of the population had been exposed to SARS-CoV-2 infection. MethodsWe conducted a cost-effectiveness analysis of COVID-19 vaccine in Kenya from a societal perspective over a 1.5-year time frame. An age-structured transmission model assumed at least 80% of the population to have prior natural immunity when an immune escape variant was introduced. We examine the effect of slow (18 months) or rapid (6 months) vaccine roll-out with vaccine coverage of 30%, 50% or 70% of the adult (> 18 years) population prioritizing roll-out in over 50-year olds (80% uptake in all scenarios). Cost data were obtained from primary analyses. We assumed vaccine procurement at $7 per dose and vaccine delivery costs of $3.90-$6.11 per dose. The cost-effectiveness threshold was USD 919. FindingsSlow roll-out at 30% coverage largely targets over 50-year-olds and resulted in 54% fewer deaths (8,132(7,914 to 8,373)) than no vaccination and was cost-saving (ICER=US$-1,343 (-1,345 to - 1,341) per DALY averted). Increasing coverage to 50% and 70%, further reduced deaths by 12% (810 (757 to 872) and 5% (282 (251 to 317) but was not cost-effective, using Kenyas cost-effectiveness threshold ($ 919.11). Rapid roll-out with 30% coverage averted 63% more deaths and was more cost-saving (ICER=$-1,607 (-1,609 to -1,604) per DALY averted) compared to slow roll-out at the same coverage level, but 50% and 70% coverage scenarios were not cost-effective. InterpretationWith prior exposure partially protecting much of the Kenyan population, vaccination of young adults may no longer be cost-effective. KEY QUESTIONSO_ST_ABSWhat is already known?C_ST_ABSO_LIThe COVID-19 pandemic has led to a substantial number of cases and deaths in low-and middle-income countries. C_LIO_LICOVID-19 vaccines are considered the main strategy of curtailing the pandemic. However, many African nations are still at the early phase of vaccination. C_LIO_LIEvidence on the cost-effectiveness of COVID-19 vaccines are useful in estimating value for money and illustrate opportunity costs. However, there is a need to balance these economic outcomes against the potential impact of vaccination. C_LI What are the new findings?O_LIIn Kenya, a targeted vaccination strategy that prioritizes those of an older age and is deployed at a rapid rollout speed achieves greater marginal health impacts and is better value for money. C_LIO_LIGiven the existing high-level population protection to COVID-19 due to prior exposure, vaccination of younger adults is less cost-effective in Kenya. C_LI What do the new findings imply?O_LIRapid deployment of vaccines during a pandemic averts more cases, hospitalisations, and deaths and is more cost-effective. C_LIO_LIAgainst a context of constrained fiscal space for health, it is likely more prudent for Kenya to target those at severe risk of disease and possibly other vulnerable populations rather than to the whole population. C_LI

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

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 specificity 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. Kenyas 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 (61.8%), the capital city, and lower in two rural regions. Almost half of Kenyas 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.

COVID-19 Transmission Dynamics Underlying Epidemic Waves in Kenya

Policy decisions on COVID-19 interventions should be informed by a local, regional and national understanding of SARS-CoV-2 transmission. Epidemic waves may result when restrictions are lifted or poorly adhered to, variants with new phenotypic properties successfully invade, or when infection spreads to susceptible sub-populations. Three COVID-19 epidemic waves have been observed in Kenya. Using a mechanistic mathematical model we explain the first two distinct waves by differences in contact rates in high and low social-economic groups, and the third wave by the introduction of a new higher-transmissibility variant. Reopening schools led to a minor increase in transmission between the second and third waves. Our predictions of current population exposure in Kenya ([~]75% June 1st) have implications for a fourth wave and future control strategies. One Sentence SummaryCOVID-19 spread in Kenya is explained by mixing heterogeneity and a variant less constrained by high population exposure

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

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. One-Sentence SummaryMixture models reduce biases inherent in the standard threshold-based analysis of SARS-CoV-2 serological data.

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

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.

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

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

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

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.