Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity (preprint)

SUMMARY SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children. Key words: SARS-CoV-2, Children, IgG responses, T cell response, Polyfunctional profile, endemic HCoV

Risk factors for severe COVID-19 among HIV-infected and-uninfected individuals in South Africa, April 2020- March 2022:data from sentinel surveillance. (preprint)

Background Data on risk factors for COVID-19-associated hospitalisation and mortality in high HIV prevalence settings are limited. Methods Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalisation and mortality. Results From April 2020 through March 2022, SARS-CoV-2 was detected in 24.0% (660/2746) of outpatient and 32.5% (2282/7025) of inpatient cases. Factors associated with COVID-19-associated hospitalisation included: older age (25-44 [adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.1-2.9], 45-64 [aOR 6.8, 95%CI 4.2-11.0] and [≥]65 years [aOR 26.6, 95%CI 14.4-49.1] vs 15-24 years); black race (aOR 3.3, 95%CI 2.2-5.0); obesity (aOR 2.3, 95%CI 1.4-3.9); asthma (aOR 3.5, 95%CI 1.4-8.9); diabetes mellitus (aOR 5.3, 95%CI 3.1-9.3); HIV with CD4 [≥]200/mm3 (aOR 1.5, 95%CI 1.1-2.2) and CD4<200/mm3 (aOR 10.5, 95%CI 5.1-21.6) or tuberculosis (aOR 12.8, 95%CI 2.8-58.5). Infection with Beta (aOR 0.5, 95%CI 0.3-0.7) vs Delta variant and being fully vaccinated (aOR 0.1, 95%CI 0.1-0.3) were less associated with COVID-19 hospitalisation. In-hospital mortality was increased in older age (45-64 years [aOR 2.2, 95%CI 1.6-3.2] and [≥]65 years [aOR 4.0, 95%CI 2.8-5.8] vs 25-44 years) and male sex (aOR1.3, 95%CI 1.0-1.6) and was lower in Omicron -infected (aOR 0.3, 95%CI 0.2-0.6) vs Delta-infected individuals. Conclusion Active syndromic surveillance encompassing clinical, laboratory and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly, people with tuberculosis or people living with HIV, especially severely immunosuppressed should be prioritised for vaccination.

Natural and hybrid immunity following four COVID-19 waves in a South African cohort (preprint)

Background: More than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity. Methods: A prospective cohort study in a South African community through the ancestral/beta/delta/omicron SARS-CoV-2 waves. Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG). To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults. Findings: Despite little disease, 176/339 (51.9%) participants were seropositive following wave 1, rising to 74%, 89.8% and 97.3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and the least for omicron. Vaccination induced higher CoV2-SIgG in seropositive compared to naive vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI:7, 14) in unvaccinated during the omicron wave. Interpretation: Naturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naive vaccinee and thus may provide adequate protection.