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

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.

COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa: An observational cohort study during 2020-2022

“…Our adjustment for prior SARS-CoV-2 infections was also extremely limited – there was substantial under-ascertainment of infections in the WC throughout the pandemic, which likely increased with the emergence of the Omicron lineage. 6 Second, low booster uptake limited our ability to assess the effectiveness of boosters themselves or distinguish between homologous/heterologous boosting. 14 Third, there may be misclassification of outcomes.…”

“…An admission or death was deemed COVID-19 related if sufficiently close to the SARS-CoV-2 diagnosis date, with no record of non-natural causes – see definitions in Appendix A2 . SARS-CoV-2 testing was extremely limited in SA: seroprevalence studies suggest approximately 1 in 10 infections were diagnosed, 6 and there was negligible use of self-tests during the study period. Therefore, ‘any SARS-CoV-2 diagnosis’ was not studied as an outcome.…”

COVID-19 Vaccine Uptake and Effectiveness by Time since Vaccination in the Western Cape Province, South Africa: An Observational Cohort Study during 2020–2022

“…For example, from a healthy vaccinee bias (inflating VE measures) [ 30 ] or greater health-seeking behaviour for COVID-19 disease among the vaccinated (deflating VE measures). Our adjustment for prior SARS-CoV-2 infections was also extremely limited—there was substantial under-ascertainment of infections in the WC throughout the pandemic, which likely increased with the emergence of the Omicron lineage [ 14 ]. Second, low booster uptake limited our ability to assess the effectiveness of boosters themselves or distinguish between homologous/heterologous boosting.…”

“…An admission or death was deemed COVID-19-related if sufficiently close to the SARS-CoV-2 diagnosis date with no record of non-natural causes—see definitions in Section S1.2 of Supplementary Material File S1 . SARS-CoV-2 testing was extremely limited in SA: seroprevalence studies suggest approximately 1 in 10 infections were diagnosed [ 14 , 15 ], and there was negligible use of self-tests during the study period. Therefore, ‘any SARS-CoV-2 diagnosis’ was not studied as an outcome.…”

“…However, the value of continued provision of vaccination opportunities is unclear in Africa and low- and middle-income countries (LMICs) where there were high levels of infection before vaccination became available [ 8 ]; achieving primary vaccine and especially booster uptake has been challenging [ 9 ], and there are competing health service priorities such as HIV and tuberculosis, many of which were adversely affected during the COVID-19 pandemic [ 10 , 11 , 12 , 13 ]. While most of those vaccinated in LMICs are likely to have hybrid immunity (prior infection and vaccination) [ 8 , 14 , 15 ], which has been shown to provide the most durable protection against severe disease in high-income country studies, there are few studies of long-term vaccine effectiveness in the context of very high levels of infection before vaccine availability, as experienced in countries such as South Africa (SA) [ 2 ]. While a health insurance scheme in SA showed rapid waning of protection of BNT162b2 vaccination against severe disease, with restoration by booster vaccination, applicability to the uninsured, poorer population is unclear [ 16 ].…”