This study assesses the durability of severe acute respiratory coronavirus-2 (SARS-CoV-2) anti-nucleocapsid (anti-N) immunoglobulin G (IgG) after infection and examines its association with established risk factors among South African healthcare workers (HCWs). Blood samples were obtained from 390 HCWs with diagnosis of coronavirus disease 2019 (COVID-19) for assay of the SARS-CoV-2 anti-N IgG at two time points (Phase 1 and 2) between November 2020 and February 2021. Out of 390 HCWs with a COVID-19 diagnosis, 267 (68.5%) had detectable SARS-CoV-2 anti-N IgG antibodies at the end of Phase I. These antibodies persisted for 4–5 and 6–7 months in 76.4% and 16.1%, respectively. In the multivariate logistic regression model analysis, Black participants were more likely to sustain SARS-CoV-2 anti-N IgG for 4–5 months. However, participants who were HIV positive were less likely to sustain SARS-CoV-2 anti-N IgG antibodies for 4–5 months. In addition, individuals who were <45 years of age were more likely to sustain SARS-CoV-2 anti-N IgG for 6–7 months. Of the 202 HCWs selected for Phase 2, 116 participants (57.4%) had persistent SARS-CoV-2 anti-N IgG for an extended mean period of 223 days (7.5 months). Findings support the longevity of vaccine responses against SARS-CoV-2 in Black Africans.