Above all, vaccination campaigns, and eventually the development of fresh vaccines could consider this potential original antigenic sin (OAS) in certain populations. neutralizing antibodies to evaluate their potential for pre-pandemic protective acquired immunity against SARS-CoV-2. In conclusion, our results suggest that, in the investigated African sub-regions, the tested populations could have been potentially and partially pre-exposed, before the COVID-19 pandemic, to the antigens of a yet non-identified Coronaviruses. Keywords: SARS-CoV-2, COVID-19, CoviDiag, natural immunity, unique antigenic sin, Africa 1. Intro The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) and, its immediate result, the pandemic Coronavirus disease 2019 (COVID-19) will have been the cause, on a global scale, of disruptions in many industries of health and societies, as well as the economy, and plans of claims [1,2]. Beyond these common impacts of the pandemic in the global level, designated variations have been observed in the above-mentioned industries [3] and medical exposure depending on populations and general public health systems [4]. Indeed, these short- and long-term manifestations are to be considered according to the areas and populations affected since the numerous factors fundamentally linked to the risk of exposure of the populations to the disease and, in the long run, to the response of the claims Citraconic acid to the pandemic. Therefore, these differences are observed in several areas and in the risk of exposure and the immune response. Indeed, more than two years after the emergence of COVID-19, in terms of the incidence of the disease, significant regional variations persist, showing the lowest incidence rates in sub-Saharan Africa, Southeast Asia, and Oceania. Such a tendency was observed in the onset of the epidemic and confirmed during subsequent Citraconic acid epidemic waves [5]. In order to clarify this circumstance, several hypotheses have been proposed, including: the morbidity and mortality counts likely to be Citraconic acid underestimated in some low- and middle-income countries due to limited epidemiological monitoring or general public health testing activity [6]; the population in sub-Saharan Africa becoming younger, with only 2.3% of the population over 65 years of age, whereas in Europe, those over 65 years of age represent 20% of the population with more than 75% of mortality associated with COVID-19 [7]; more rural living conditions potentially increasing sociable distancing and reducing the spread of the disease; climatic and environmental factors unfavorable to the disease persistence and spread [8]; a natural innate non-specific immunity, or, as an original antigenic sin (OAS), an immune response secondary to a earlier contact with a Sarbecovirus related to the SARS-CoV-2 coronavirus posting common antigenic profiles. For a brief reminder, coronavirus genome encodes four major structural proteins including the spike (S), nucleocapsid (N), envelope (E) and, membrane (M) proteins. The transmembrane glycoprotein S takes on an essential part in virus-cell illness. It comprises two practical subunits: the S1 subunit binding protein, and the fusion S2 subunit. The S1 subunit is definitely divided Gimap5 into an N-terminal website (NTD) and a receptor binding website (RBD) responsible for binding the disease to the sponsor cell Angiotensin-Converting Enzyme 2 (ACE2) receptor binding website [9,10]. The N protein is definitely involved in the externalization of viral particles from the infected cell [11]. Indeed, all the human being viral varieties (e.g., SARS-CoV-1, SARS-CoV-2) or animal varieties (e.g., chiropterans especially) of the Sarbecovirus subgenus have the same antigenic structure and a very close genomic material, having a homology of more than 80%. Further, the SARS-CoV-2 genome Citraconic acid is definitely closely related to SARS-CoV-1 (79.6% of homology) and several antibodies covering all structural proteins of SARS-CoV (S, M, N, E) have been.