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Background: Because the regular vaccine campaign started in Guinea one year after the COVID-19 index case, the profile of naturally acquired immunity following primary SARS-CoV-2 infection needs to be deepened. Methods: Blood samples were collected once from 200 patients (90% of African extraction) who were recovered from COVID-19 for at least ~2.4 months (72 days), and their sera were tested for IgG antibodies to SARS-CoV-2 using an in-house ELISA assay against the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike1 protein (RBD/S1-IH kit). Results: Results revealed that 73% of sera (146/200) were positive for IgG to SARS-CoV-2 with an Optical Density (OD) ranging from 0.13 to 1.19 and a median value of 0.56 (IC95: 0.51–0.61). The median OD value at 3 months (1.040) suddenly decreased thereafter and remained stable around OD 0.5 until 15 months post-infection. The OD median value was slightly higher in males compared to females (0.62 vs. 0.49), but the difference was not statistically significant (p-value: 0.073). In contrast, the OD median value was significantly higher among the 60–100 age group (0.87) compared to other groups, with a noteworthy odds ratio compared to the 0–20 age group (OR: 9.69, p-value: 0.044*). Results from the RBD/S1-IH ELISA kit demonstrated superior concordance with the whole spike1 protein ELISA commercial kit compared to a nucleoprotein ELISA commercial kit. Furthermore, anti-spike1 protein ELISAs (whole spike1 and RBD/S1) revealed higher seropositivity rates. Conclusions: These findings underscore the necessity for additional insights into naturally acquired immunity against COVID-19 and emphasize the relevance of specific ELISA kits for accurate seropositivity rates [ABSTRACT FROM AUTHOR]