Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults.

BackgroundSARS-CoV-2 infection in Africa has been characterized by a less severe disease profile than what has been observed elsewhere, but the profile of SARS-CoV-2-specific adaptive immunity in these mainly asymptomatic patients has not, to our knowledge, been analyzed.MethodsWe collected blood samples from residents of rural Kenya (n = 80), who had not experienced any respiratory symptoms or had contact with individuals with COVID-19 and had not received COVID-19 vaccines. We analyzed spike-specific antibodies and T cells specific for SARS-CoV-2 structural (membrane, nucleocapsid, and spike) and accessory (ORF3a, ORF7, ORF8) proteins. Pre-pandemic blood samples collected in Nairobi (n = 13) and blood samples from mild-to-moderately symptomatic COVID-19 convalescent patients (n = 36) living in the urban environment of Singapore were also studied.ResultsAmong asymptomatic Africans, we detected anti-spike antibodies in 41.0% of the samples and T cell responses against 2 or more SARS-CoV-2 proteins in 82.5% of samples examined. Such a pattern was absent in the pre-pandemic samples. Furthermore, distinct from cellular immunity in European and Asian COVID-19 convalescents, we observed strong T cell immunogenicity against viral accessory proteins (ORF3a, ORF8) but not structural proteins, as well as a higher IL-10/IFN-γ cytokine ratio profile.ConclusionsThe high incidence of T cell responses against different SARS-CoV-2 proteins in seronegative participants suggests that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. The functional and antigen-specific profile of SARS-CoV-2-specific T cells in African individuals suggests that environmental factors can play a role in the development of protective antiviral immunity.FundingUS Centers for Disease Control and Prevention, Division of Global Health Protection; the Singapore Ministry of Health's National Medical Research Council (COVID19RF3-0060, COVID19RF-001, COVID19RF-008, MOH-StaR17Nov-0001).

Healthcare-seeking behavior for respiratory illnesses in Kenya: implications for burden of disease estimation.

BACKGROUND: Understanding healthcare-seeking patterns for respiratory illness can help improve estimation of disease burden and target public health interventions to control acute respiratory disease in Kenya. METHODS: We conducted a cross-sectional survey to determine healthcare utilization patterns for acute respiratory illness (ARI) and severe pneumonia in four diverse counties representing urban, peri-urban, rural mixed farmers, and rural pastoralist communities in Kenya using a two-stage (sub-locations then households) cluster sampling procedure. Healthcare seeking behavior for ARI episodes in the last 14 days, and severe pneumonia in the last 12 months was evaluated. Severe pneumonia was defined as reported cough and difficulty breathing for > 2 days and report of hospitalization or recommendation for hospitalization, or a danger sign (unable to breastfeed/drink, vomiting everything, convulsions, unconscious) for children < 5 years, or report of inability to perform routine chores. RESULTS: From August through September 2018, we interviewed 28,072 individuals from 5,407 households. Of those surveyed, 9.2% (95% Confidence Interval [CI] 7.9-10.7) reported an episode of ARI, and 4.2% (95% CI 3.8-4.6) reported an episode of severe pneumonia. Of the reported ARI cases, 40.0% (95% CI 36.8-43.3) sought care at a health facility. Of the74.2% (95% CI 70.2-77.9) who reported severe pneumonia and visited a medical health facility, 28.9% (95% CI 25.6-32.6) were hospitalized and 7.0% (95% CI 5.4-9.1) were referred by a clinician to the hospital but not hospitalized. 21% (95% CI 18.2-23.6) of self-reported severe pneumonias were hospitalized. Children aged < 5 years and persons in households with a higher socio-economic status were more likely to seek care for respiratory illness at a health facility. CONCLUSION: Our findings suggest that hospital-based surveillance captures less than one quarter of severe pneumonia in the community. Multipliers from community household surveys can account for underutilization of healthcare resources and under-ascertainment of severe pneumonia at hospitals.

Near-Complete SARS-CoV-2 Seroprevalence among Rural and Urban Kenyans despite Significant Vaccine Hesitancy and Refusal.

Considering the early inequity in global COVID-19 vaccine distribution, we compared the level of population immunity to SARS-CoV-2 with vaccine uptake and refusal between rural and urban Kenya two years after the pandemic onset. A population-based seroprevalence study was conducted in the city of Nairobi (n = 781) and a rural western county (n = 810) between January and February 2022. The overall SARS-CoV-2 seroprevalence was 90.2% (95% CI, 88.6−91.2%), including 96.7% (95% CI, 95.2−97.9%) among urban and 83.6% (95% CI, 80.6−86.0%) among rural populations. A comparison of immunity profiles showed that >50% of the rural population were strongly immunoreactive compared to <20% of the urban population, suggesting more recent infections or vaccinations in the rural population. More than 45% of the vaccine-eligible (≥18 years old) persons had not taken a single dose of the vaccine (hesitancy), including 47.6% and 46.9% of urban and rural participants, respectively. Vaccine refusal was reported in 19.6% of urban and 15.6% of rural participants, attributed to concern about vaccine safety (>75%), inadequate information (26%), and concern about vaccine effectiveness (9%). Less than 2% of vaccine refusers cited religious or cultural beliefs. These findings indicate that despite vaccine inequity, hesitancy, and refusal, herd immunity had been achieved in Kenya and likely other African countries by early 2022, with natural infections likely contributing to most of this immunity. However, vaccine campaigns should be sustained due to the need for repeat boosters associated with waning of SARS-CoV-2 immunity and emergence of immune-evading virus variants.

Characterization of COVID-19 cases in the early phase (March to July 2020) of the pandemic in Kenya.

Background: Kenya detected the first case of COVID-19 on March 13, 2020, and as of July 30, 2020, 17 975 cases with 285 deaths (case fatality rate (CFR) = 1.6%) had been reported. This study described the cases during the early phase of the pandemic to provide information for monitoring and response planning in the local context. Methods: We reviewed COVID-19 case records from isolation centres while considering national representation and the WHO sampling guideline for clinical characterization of the COVID-19 pandemic within a country. Socio-demographic, clinical, and exposure data were summarized using median and mean for continuous variables and proportions for categorical variables. We assigned exposure variables to socio-demographics, exposure, and contact data, while the clinical spectrum was assigned outcome variables and their associations were assessed. Results: A total of 2796 case records were reviewed including 2049 (73.3%) male, 852 (30.5%) aged 30-39 years, 2730 (97.6%) Kenyans, 636 (22.7%) transporters, and 743 (26.6%) residents of Nairobi City County. Up to 609 (21.8%) cases had underlying medical conditions, including hypertension (n = 285 (46.8%)), diabetes (n = 211 (34.6%)), and multiple conditions (n = 129 (21.2%)). Out of 1893 (67.7%) cases with likely sources of exposure, 601 (31.8%) were due to international travel. There were 2340 contacts listed for 577 (20.6%) cases, with 632 contacts (27.0%) being traced. The odds of developing COVID-19 symptoms were higher among case who were aged above 60 years (odds ratio (OR) = 1.99, P = 0.007) or had underlying conditions (OR = 2.73, P < 0.001) and lower among transport sector employees (OR = 0.31, P < 0.001). The odds of developing severe COVID-19 disease were higher among cases who had underlying medical conditions (OR = 1.56, P < 0.001) and lower among cases exposed through community gatherings (OR = 0.27, P < 0.001). The odds of survival of cases from COVID-19 disease were higher among transport sector employees (OR = 3.35, P = 0.004); but lower among cases who were aged ≥60 years (OR = 0.58, P = 0.034) and those with underlying conditions (OR = 0.58, P = 0.025). Conclusion: The early phase of the COVID-19 pandemic demonstrated a need to target the elderly and comorbid cases with prevention and control strategies while closely monitoring asymptomatic cases.

COVID-19 Knowledge, Attitudes and Practices and Vaccine Acceptability in Rural Western Kenya and an Urban Informal Settlement in Nairobi, Kenya: A Cross-Sectional Survey

An important step towards COVID-19 pandemic control is adequate knowledge and adherence to mitigation measures, including vaccination. We assessed the level of COVID-19 knowledge, attitudes, and practices (KAP) among residents from an urban informal settlement in the City of Nairobi (Kibera), and a rural community in western Kenya (Asembo). A cross-sectional survey was implemented from April to May 2021 among randomly selected adult residents from a population-based infectious diseases surveillance (PBIDS) cohort in Nairobi and Siaya Counties. KAP questions were adopted from previous studies. Factors associated with the level of COVID-19 KAP, were assessed using multivariable regression methods. COVID-19 vaccine acceptance was 83.6% for the participants from Asembo and 59.8% in Kibera. The reasons cited for vaccine hesitancy in Kibera were safety concerns (34%), insufficient information available to decide (18%), and a lack of belief in the vaccine (21%), while the reasons in Asembo were safety concerns (55%), insufficient information to decide (26%) and lack of belief in the vaccine (11%). Our study findings suggest the need for continued public education to enhance COVID-19 knowledge, attitudes, and practices to ensure adherence to mitigation measures. Urban informal settlements require targeted messaging to improve vaccine awareness, acceptability, and uptake.

Outbreak of Middle East Respiratory Syndrome Coronavirus in Camels and Probable Spillover Infection to Humans in Kenya.

The majority of Kenya's > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0-24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April-September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.

Imported SARS-CoV-2 Variants of Concern Drove Spread of Infections across Kenya during the Second Year of the Pandemic

Using classical and genomic epidemiology, we tracked the COVID-19 pandemic in Kenya over 23 months to determine the impact of SARS-CoV-2 variants on its progression. SARS-CoV-2 surveillance and testing data were obtained from the Kenya Ministry of Health, collected daily from 306 health facilities. COVID-19-associated fatality data were also obtained from these health facilities and communities. Whole SARS-CoV-2 genome sequencing were carried out on 1241 specimens. Over the pandemic duration (March 2020–January 2022), Kenya experienced five waves characterized by attack rates (AR) of between 65.4 and 137.6 per 100,000 persons, and intra-wave case fatality ratios (CFR) averaging 3.5%, two-fold higher than the national average COVID-19 associated CFR. The first two waves that occurred before emergence of global variants of concerns (VoC) had lower AR (65.4 and 118.2 per 100,000). Waves 3, 4, and 5 that occurred during the second year were each dominated by multiple introductions each, of Alpha (74.9% genomes), Delta (98.7%), and Omicron (87.8%) VoCs, respectively. During this phase, government-imposed restrictions failed to alleviate pandemic progression, resulting in higher attack rates spread across the country. In conclusion, the emergence of Alpha, Delta, and Omicron variants was a turning point that resulted in widespread and higher SARS-CoV-2 infections across the country.

High seroprevalence of SARS-CoV-2 but low infection fatality ratio eight months after introduction in Nairobi, Kenya.

BACKGROUND: The lower than expected COVID-19 morbidity and mortality in Africa has been attributed to multiple factors, including weak surveillance. This study estimated the burden of SARS-CoV-2 infections eight months into the epidemic in Nairobi, Kenya. METHODS: A population-based, cross-sectional survey was conducted using multi-stage random sampling to select households within Nairobi in November 2020. Sera from consenting household members were tested for antibodies to SARS-CoV-2. Seroprevalence was estimated after adjusting for population structure and test performance. Infection fatality ratios (IFRs) were calculated by comparing study estimates with reported cases and deaths. RESULTS: Among 1,164 individuals, the adjusted seroprevalence was 34.7% (95% CI 31.8-37.6). Half of the enrolled households had at least one positive participant. Seropositivity increased in more densely populated areas (spearman's r=0.63; p=0.009). Individuals aged 20-59 years had at least two-fold higher seropositivity than those aged 0-9 years. The IFR was 40 per 100,000 infections, with individuals ≥60 years old having higher IFRs. CONCLUSION: Over one-third of Nairobi residents had been exposed to SARS-CoV-2 by November 2020, indicating extensive transmission. However, the IFR was >10-fold lower than that reported in Europe and the USA, supporting the perceived lower morbidity and mortality in sub-Saharan Africa.

Why is There Low Morbidity and Mortality of COVID-19 in Africa?

Three months since the detection of the first COVID-19 case in Africa, almost all countries of the continent continued to report lower morbidity and mortality than the global trend, including Europe and North America. We reviewed the merits of various hypotheses advanced to explain this phenomenon, including low seeding rate, effective mitigation measures, population that is more youthful, favorable weather, and possible prior exposure to a cross-reactive virus. Having a youthful population and favorable weather appears compelling, particularly their combined effect; however, progression of the pandemic in the region and globally may dispel these in the coming months.