Anti-inflammatory SARS-CoV-2 T cell immunity in asymptomatic seronegative Kenyan adults

Antibodies are used to estimate prevalence of past infection. However, T cell responses against SARS-CoV-2 may more accurately define prevalence because SARS-CoV-2-specific antibodies wane. In November-December 2021, we studied serological and cellular immune responses in residents of rural Kenya who had not experienced any respiratory symptom nor had contact with COVID-19 cases. Among participants we detected anti-spike antibodies in 41.0% and T cell responses against ≥2 SARS-CoV-2 proteins in 82.5%, which implies that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. Distinct from cellular immunity in European and Asian COVID-19 convalescents, strong T cell immunogenicity was observed against viral accessory proteins in these asymptomatic Africans, as well as a higher IL-10/IFN-γ ratio cytokine profile, suggesting that environmental or genetic factors modulate pro-inflammatory responses. Funding U.S. Centers for Disease Control and Prevention, Division of Global Health Protection. Singapore Ministry of Health’s National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060, COVID19RF-001 and COVID19RF-008) and the Singapore Ministry of Health’s National Medical Research Council MOH-000019 (MOH-StaR17Nov-0001). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by U.S. Centers for Disease Control and Prevention Division of Global Health Protection. Singapore Ministry of Health National Medical Research Council COVID-19 Research Fund COVID19RF3-0060. Singapore Ministry of Health National Medical Research Council COVID-19 Research Fund COVID19RF-001. Singapore Ministry of Health National Medical Research Council COVID-19 Research Fund COVID19RF-008. Singapore Ministry of Health National Medical Research Council MOH-000019 (MOH-StaR17Nov-0001) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Kenya Medical Research Institute gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data produced in the present study are available upon reasonable request to the authors