HIGHER CORONAVIRUS ANTIBODY RESPONSES PREPANDEMIC in AFRICA THAN in THAILAND

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.