Spike protein is a key target for stronger and more persistent T-cell responses-a study of mild and asymptomatic SARS-CoV-2 infection.

OBJECTIVES: Understanding the immune response in very mild and asymptomatic COVID-19 is crucial for developing effective vaccines and immunotherapies, yet remains poorly characterized. This longitudinal study examined the evolution of interferon (IFN)-γ responses to SARS-CoV-2 peptides in 109 asymptomatic or mildly symptomatic Ugandan COVID-19 patients across 365 days and explored their association with antibody generation. METHODS: T-cell responses to spike-containing clusters of differentiation (CD4)-S and CD8 nCoV-A (CD8-A) megapools, and the non-spike CD4-R and CD8 nCoV-B (CD8-B) megapools, were assessed and correlated with demographic and temporal variables. RESULTS: SARS-CoV-2-specific IFN-γ responses were consistently detected in all peptide pools and time points, with the spike-targeted response exhibiting higher potency and durability than the non-spike responses. Throughout the entire 365-day infection timeline, a robust positive correlation was observed between CD4 T-cell responses to the spike-derived peptides and anti-spike immunoglobulin G antibody levels, underscoring their interdependent dynamics in the immune response against SARS-CoV-2; in contrast, CD8 T-cell responses exhibited no such correlation, highlighting their distinctive, autonomous role in defense. No meaningful variations in complete blood count parameters were observed between individuals with COVID-19 infection and those without, indicating clinical insignificance. CONCLUSIONS: This study highlights the dominant role of spike-directed T-cell responses in mild and asymptomatic disease and provides crucial longitudinal data from Sub-Saharan African settings. The findings provide valuable insights into the dynamics of T-cell responses and their potential significance in developing effective strategies for combating COVID-19.

Seroprevalence and durability of antibody responses to AstraZeneca vaccination in Ugandans with prior mild or asymptomatic COVID-19: implications for vaccine policy.

Introduction: The duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan Africa are crucial for guiding pandemic policy interventions, but systematic data for this region is scarce. This study investigated the antibody response after AstraZeneca vaccination in COVID-19 convalescent Ugandans. Methods: We recruited 86 participants with a previous rt-PCR-confirmed mild or asymptomatic COVID-19 infection and measured the prevalence and levels of spike-directed IgG, IgM, and IgA antibodies at baseline, 14 and 28 days after the first dose (priming), 14 days after the second dose (boosting), and at six- and nine-months post-priming. We also measured the prevalence and levels of nucleoprotein-directed antibodies to assess breakthrough infections. Results: Within two weeks of priming, vaccination substantially increased the prevalence and concentrations of spike-directed antibodies (p < 0.0001, Wilcoxon signed rank test), with 97.0% and 66% of vaccinated individuals possessing S-IgG and S-IgA antibodies before administering the booster dose. S-IgM prevalence changed marginally after the initial vaccination and barely after the booster, consistent with an already primed immune system. However, we also observed a rise in nucleoprotein seroprevalence, indicative of breakthroughs six months after the initial vaccination. Discussion: Our results suggest that vaccination of COVID-19 convalescent individuals with the AstraZeneca vaccine induces a robust and differential spike-directed antibody response. The data highlights the value of vaccination as an effective method for inducing immunity in previously infected individuals and the importance of administering two doses to maintain protective immunity. Monitoring anti-spike IgG and IgA when assessing vaccine-induced antibody responses is suggested for this population; assessing S-IgM will underestimate the response. The AstraZeneca vaccine is a valuable tool in the fight against COVID-19. Further research is needed to determine the durability of vaccine-induced immunity and the potential need for booster doses.

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months.

Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines. Methods: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months. Results: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout. Discussion: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.