Epidemiology and outcomes of SARS-CoV-2 infection associated with anti-nucleocapsid seropositivity in Cape Town, South Africa

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Abstract Background In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods We conducted repeated cross-sectional serosurveys (July 2020 – November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Findings Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). Interpretation The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19. Funding Wellcome Trust, National Health Laboratory Service, the Division of Intramural Research, NIAID, NIH (ADR) and Western Cape Government Health. Research in context Evidence before this study In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe the true extent of the pandemic. Infection from Omicron was associated with less severe disease in South Africa, but it is unclear whether this was due to a decrease in virulence of the variant or if prior infection provided protection. Added value of this study The seroprevalence data nested within a population cohort enabled us to assess differential case ascertainment rates, as well as to examine the contribution of both natural and vaccine-induced immunity in protecting communities against infections and severe disease with different SARS-CoV-2 variants. Implications of the available evidence Inequality and differential access to resources resulted in poorer communities having higher seroprevalence and COVID-19 death rates, with lower case ascertainment rates. Antibody positivity provided strong protection against an immune escape variant like Omicron but came at a high mortality cost.

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