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Pre-pandemic SARS-CoV-2 potential natural immunity among population of the Democratic Republic of Congo

More than a year after the emergence of COVID-19, significant regional differences in terms of morbidity persist, showing lower incidence rates in sub-Saharan Africa, Southeast Asia, and Oceania. Like SARS-CoV-1 and MERS viruses, SARS-CoV-2 is monophyletically positioned with parental species of chiropteran coronavirus. Furthermore, we observe that the spatial distribution of several targeted bat species (i.e., Coronavirus species hosts) overlaps the distribution of countries with low COVID-19 incidence. The work presented here aims to test the presence of natural immunity among population with a low COVD-19 prevalence, potentially due to a previous exposure to coronavirus antigens of a virus close related to SARS-CoV-2. To identify such pre-existing immunity, an ELISA serological test was used to detect IgG antibodies targeting main SARS-CoV-2 proteins including: the N-protein, the Spike 1 (S1) protein, the receptor binding domain (RBD) of the S1 protein, the N-terminal domain (NTD) of the S1 protein, and the S2 protein. A total of 574 sera samples collected before 2019 in the population of the Democratic Republic of Congo (DRC) were tested). 189 control sera from blood donors in France were used as control samples. The results showed a statistically significant difference between the DRC samples and control samples for all antigens (N, S1, S2, NTD) except for RBD. The percentage of positive samples presenting reactive antibodies for S1 antigen was respectively of 19.2% for RDC versus 2.11% for the control, and of 9.3% versus 1.6% for the S2 antigen. In conclusion, our data showed that the study population has been potentially exposed to a SARS-CoV-2-like virus antigen before the pandemic in the Central African sub-region. Therefore, it is quite legitimate to think that this prior immunity may be protective and responsible for the observed low prevalence of COVID-19. Moreover, we can assume that this not yet identified SARS-CoV-2-like could be associated to a chiropteran species in close contact with the studied population. In order to confirm the presence of SARS-CoV-2-like virus antibodies and ultimately identify the neutralizing potential for the detected antibodies, our study is underway in other African and Asian countries, where the COVID-19 prevalence is limited.