ABSTRACT
Background: Pre-existing coronavirus-specific antibody responses may affect SARS-CoV-2 responses. We evaluated longitudinal samples obtained before and during the pandemic in participants from Kenya, Nigeria, Tanzania and Uganda;90% were people living with HIV. Method(s): Serum samples were tested using a multiplex bead-based immunoassay to measure antibody binding against 22 antigens including Nucleocapsid (N) and Spike (S) proteins of the 7 human coronaviruses and one malaria antigen. Result(s): We tested 819 longitudinal samples from 80 participants collected between July 2013 and May 2021 (3-16 samples per participant). Using a signal to noise ratio (S/N) >10, 13, 1, and 5 participants showed at least one time point with IgG responses to S of SARS-CoV-2 (ancestral), SARS-CoV-1 and MERS-CoV respectively while 14, 8, and 11 participants showed responses to N before 2020. Across individuals, IgG binding to SARS-CoV-2 S subunit S2 was most frequently detected and it showed the highest within-host fluctuations over time. A few individuals had elevated responses that persisted over years towards multiple antigens, most frequently to different SARS-CoV-2 antigens and rarely to distinct viruses. One individual showed high RBD-specific IgG responses to distinct coronaviruses at a single time point before 2020. Responses against coronaviruses measured post-2020 generally correlated with responses measured before 2020, except for a subset of infected individuals whose responses against SARS-CoV-2 dramatically increased post-pandemic. IgG responses against the ancestral SARS-CoV-2 variant were most correlated with responses against Alpha and Gamma (then to Beta and Delta, rho >0.75) variants. Using an IgM S/N >10, 31 participants were Malaria positive and 22 showed concurrent elevated coronavirus IgM responses. However, about half of the malaria positive participants had no IgG responses against any coronavirus antigen and the rest presented limited and variable patterns of association between responses against coronaviruses and malaria. Conclusion(s): Our study confirmed that a small subset of individuals in Africa had long-lasting IgG coronavirus-specific antibodies before the pandemic. While there was an association between coronavirus IgM responses and responses against malaria, there was no correlation between IgG responses and malaria infection. Further analysis is needed to better understand the interactions between antigens in the development of antibody immunity to coronaviruses. (Table Presented).
ABSTRACT
Background: COVID-19 clinical manifestations range from asymptomatic to severe disease. Prior immune responses to human coronaviruses may affect individual responses to SARS-CoV-2. We surveyed coronavirus responses pre-pandemic in individuals from Kenya, Nigeria, Tanzania, Uganda and Thailand;81% were people living with HIV. Methods: Specimens were screened for SARS-CoV-2 Spike S2 subunit IgG responses. Selected samples were tested using a bead-based immunoassay that profiled the specificity, isotype and subclass of antibody responses to coronavirus, flavivirus and HIV antigens. Wilcoxon rank sum tests were performed to compare responses across antigens and participant group. Results: We screened 1,875 samples (one per individual) collected between 2013 and October 2019: 1,630 samples were from Africa (87%) and 245 from Thailand. 6.99% of participants (n=131, 116 from Africa (89%) and 15 from Thailand) showed responses above the naïve signal threshold and were further tested. Using a signal to noise ratio of >10 as a cut-off value, 44, 27 and 42 samples showed IgG responses to the Spike protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV respectively, while 7, 9 and 4 samples showed responses to Nucleocapsid for these same antigens. Some individuals had higher responses than those seen in SARS-CoV-2 convalescent individuals. We found a strikingly different pattern of reactivity in Africa compared to Thailand (Figure 1). Antibody responses were significantly higher in the African participants compared to Thai participants across antigens corresponding to SARS-CoV-2 (p<0.001), SARS-CoV-1 (p<0.001) and MERS-CoV (p<0.01). Similar patterns were seen for IgG subclasses, IgA and IgM. The difference was less pronounced for the four endemic coronaviruses, nonetheless anti-Spike responses were significantly higher in African participants for HKU1 and OC43 (p≤0.018). In addition, mapping responses to 21 flavivirus antigens showed the highest reactivity in Thailand and in Nigeria. Conclusion: Our serosurvey of pre-pandemic samples showed that there were significantly higher antibody responses against coronaviruses, including SARS-CoV-2, in Africa than in Thailand. Profiling flavivirus responses showed that the difference between the two regions was not due to a higher background reactivity across African samples. Further analysis is needed to explain pre-pandemic SARS-CoV-2-like antibody responses among African participants and explore implications for geographic diversity in disease severity.