Prospective Clinical Surveillance for Severe Acute Respiratory Illness in Kenyan Hospitals during the COVID-19 pandemic (preprint)

There are limited data from sub-Saharan Africa describing the pattern of admissions to public hospitals with severe acute respiratory infections during the COVID-19 pandemic. We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. Demographic and clinical characteristics, COVID-19 infection and vaccination status and outcome data were collected. Of the 52,714 patients included in the study, 18,001 (35%) were admitted with severe acute respiratory illness (SARI). The mean age was 51 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, HIV and diabetes mellitus were the most common comorbidities. COVID-19 test results were positive in 2,370 (28%) of the 8,517 (47%) patients that underwent testing. Overall inpatient case fatality for SARI was 21% (n=3,828). After adjusting for age, sex and presence of a comorbidity, SARI patients had higher inpatient mortality compared to non-SARI patients regardless of their COVID-19 status (aHR 1.31, 95% CI 1.19 - 1.46). COVID-19 positive SARI patients had a higher inpatient mortality rate compared to their negative counterparts (aHR 1.31, 95% CI 1.12 - 1.54, p value < 0.0001). COVID-19 vaccine effectiveness against mortality due to SARI after adjusting for age, sex and presence of a comorbidity was 34% (95% CI 11% - 51%). We have provided a comprehensive description of the pattern of admissions with respiratory illnesses in Kenyan hospitals during the COVID-19 pandemic period. We have demonstrated the utility of routine surveillance activities within public hospitals in low-income settings which if strengthened can enhance the response to emerging health threats.

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.

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 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.