The evolution and interpretation of seroprevalence of SARS-CoV-2 antibodies among South African blood donors from the Beta to Omicron variant-driven waves.

BACKGROUND AND OBJECTIVES: Confirmed COVID-19 diagnoses underestimate the total number of infections. Blood donors can provide representative seroprevalence estimates, which can be leveraged into reasonable estimates of total infection counts and infection fatality rate (IFR). MATERIALS AND METHODS: Blood donors who donated after each of three epidemic waves (Beta, Delta and first Omicron waves) were tested for anti-SARS-CoV-2 nucleocapsid antibodies using the Roche Elecsys anti-SARS-CoV-2 total immunoglobulin assay. Roche Elecsys anti-spike antibody testing was done for the post-Omicron sampling. Prevalence of antibodies was estimated by age, sex, race and province and compared to official case reporting. Province and age group-specific IFRs were estimated using external excess mortality estimates. RESULTS: The nationally weighted anti-nucleocapsid seroprevalence estimates after the Beta, Delta and Omicron waves were 47% (46.2%-48.6%), 71% (68.8%-73.5%) and 87% (85.5%-88.4%), respectively. There was no variation by age and sex, but there were statistically and epidemiologically significant differences by province (except at the latest time point) and race. There was a 13-fold higher seroprevalence than confirmed case counts at the first time point. Age-dependent IFR roughly doubled for every 10 years of age increase over 6 decades from 0.014% in children to 6.793% in octogenarians. CONCLUSION: Discrepancies were found between seroprevalence and confirmed case counts. High seroprevalence rates found among Black African donors can be ascribed to historical inequities. Our IFR estimates were useful in refining previous large disagreements about the severity of the epidemic in South Africa. Blood donor-based serosurveys provided a valuable and efficient way to provide near real-time monitoring of the ongoing SARS-CoV-2 outbreak.

Evidence of HIV incidence reduction in young women, but not in adolescent girls, in KwaZulu-Natal, South Africa.

Objectives: We estimated changes in the HIV incidence from 2013-2018 in Eshowe/Mbongolwane, KwaZulu-Natal, South Africa where Médecins Sans Frontières is engaged in providing HIV testing and care since 2011. Methods: Using data from two cross-sectional household-based surveys conducted in 2013 and 2018, with consenting participants aged 15-59 years, we applied the incidence estimation frameworks of Mahiane et al and Kassanjee et al. Results: In total, 5599 (62.4% women) and 3276 (65.9% women) individuals were included in 2013 and 2018, respectively. We found a mean incidence in women aged 20-29 years of 2.71 cases per 100 person-years (95% confidence interval [CI]: 1.23;4.19) in 2013 and 0.4 cases per 100 person-years (95% CI: 0.0;1.5) in 2018. The incidence in men aged 20-29 years was 1.91 cases per 100 person-years (95% CI: 0.87; 2.93) in 2013 and 0.53 cases per 100 person-years (95% CI: 0.0; 1.4) in 2018. The incidence decline among women aged 15-19 was -0.34 cases per 100 person-years (95% CI: -1.31;0.64). Conclusions: The lack of evidence of incidence decline among adolescent girls is noteworthy and disconcerting. Our findings suggest that large-scale surveys should seriously consider focusing their resources on the core group of women aged 15-19 years.

The role of wastewater-based epidemiology for SARS-CoV-2 in developing countries: Cumulative evidence from South Africa supports sentinel site surveillance to guide public health decision-making.

The uptake of wastewater-based epidemiology (WBE) for SARS-CoV-2 as a complementary tool for monitoring population-level epidemiological features of the COVID-19 pandemic in low-and-middle-income countries (LMICs) is low. We report on the findings from the South African SARS-CoV-2 WBE surveillance network and make recommendations regarding the implementation of WBE in LMICs. Eight laboratories quantified influent wastewater collected from 87 wastewater treatment plants in all nine South African provinces from 01 June 2021 to 31 May 2022 inclusive, during the 3rd and 4th waves of COVID-19. Correlation and regression analyses between wastewater levels of SARS-CoV-2 and district laboratory-confirmed caseloads were conducted. The sensitivity and specificity of novel 'rules' based on WBE data to predict an epidemic wave were determined. Amongst 2158 wastewater samples, 543/648 (85 %) samples taken during a wave tested positive for SARS-CoV-2 compared with 842 positive tests from 1512 (55 %) samples taken during the interwave period. Overall, the regression-co-efficient was 0,66 (95 % confidence interval = 0,6-0,72, R2 = 0.59), ranging from 0.14 to 0.87 by testing laboratory. Early warning of the 4th wave of SARS-CoV-2 in Gauteng Province in November-December 2021 was demonstrated. A 50 % increase in log copies of SARS-CoV-2 compared with a rolling mean over the previous five weeks was the most sensitive predictive rule (58 %) to predict a new wave. Our findings support investment in WBE for SARS-CoV-2 surveillance in LMICs as an early warning tool. Standardising test methodology is necessary due to varying correlation strengths across laboratories and redundancy across testing plants. A sentinel site model can be used for surveillance networks without affecting WBE finding for decision-making. Further research is needed to identify optimal test frequency and the need for normalisation to population size to identify predictive and interpretive rules to support early warning and public health action.

Estimates of prevalence of anti-SARS-CoV-2 antibodies among blood donors in South Africa in March 2022.

In line with previous instalments of analysis from this ongoing study to monitor 'Covid Seroprevalence' among blood donors in South Africa, we report on an analysis of 3395 samples obtained in mid-March 2022 from all provinces of South Africa - a timepoint just after the fourth (primarily omicron) wave of infections. As in our previous analyses, we see no evidence of age and sex dependence of prevalence, but significant variation by race. Differences between provinces have largely disappeared, as prevalence appears to have saturated. In contrast to previous estimates from this study, which reported only prevalence of anti-nucleocapsid antibodies, this present work also reports results from testing for anti-spike antibodies. This addition allows us to categorise those donors whose only antibodies are from vaccination. Our race-weighted national extrapolation is that 98% of South Africans have some antibodies, noting that 10% have anti-spike antibodies but not anti-nucleocapsid antibodies - a reasonable proxy for having both 1) been vaccinated and 2) avoided infection.

Estimates of prevalence of anti-SARS-CoV-2 antibodies among blood donors in eight provinces of South Africa in November 2021.

In line with previous instalments of analysis from this ongoing study to monitor 'Covid Seroprevalence' among blood donors in South Africa, we report on analysis of 3395 samples obtained from 8 to 12 November 2021 in all provinces of South Africa except the Western Cape. As in our previous analyses, we see no evidence of age and sex dependence of prevalence, but substantial variation by province, and by race within each province, from which we generated provincial total point estimates (EC-74%; FS-75%; GP-68%; ZN-73%; LP-66; MP-73%; NC-63%; NW-81% ) and a 'South Africa minus Western Cape' national prevalence estimate of 71% (95%CI 69-74%). We note that sample collection occurred just before the omicron variant driven wave in South Africa, but otherwise present these results without significant interpretation.

Prevalence of anti-SARS-CoV-2 antibodies among blood donors in Northern Cape, KwaZulu-Natal, Eastern Cape, and Free State provinces of South Africa in January 2021.

Background: Population-level estimates of prevalence of anti-SARS-CoV-2 antibody positivity (seroprevalence) is a crucial epidemiological indicator for tracking the Covid-19 epidemic. Such data are in short supply, both internationally and in South Africa. The South African blood services (the South African National Blood Service, SANBS and the Western Cape Blood Service, WCBS) are coordinating a nationally representative survey of blood donors, which it is hoped can become a cost-effective surveillance method with validity for community-level seroprevalence estimation. Methods: Leveraging existing arrangements, SANBS human research ethics committee permission was obtained to test blood donations collected on predefined days (7th, 10th, 12th, 15th, 20th, 23th and 25th January) for anti-SARS-CoV-2 antibodies, using the Roche Elecsys Anti-SARS-CoV-2 assay on the cobas e411 platform currently available in the blood services' donation testing laboratories. Using standard methods, prevalence analysis was done by province, age and race, allowing age to be regarded as either a continuous or categorical variable. Testing was performed in the Eastern Cape (EC), Free State (FS), KwaZulu Natal (ZN) and Northern Cape (NC) provinces. Results: We report on data from 4858 donors - 1457 in EC; 463 in NC; 831 in FS and 2107 in ZN. Prevalence varied substantially across race groups and between provinces, with seroprevalence among Black donors consistently several times higher than among White donors, and the other main population groups (Coloured and Asian) not consistently represented in all provinces. There is no clear evidence that seroprevalence among donors varies by age. Weighted net estimates of prevalence (in the core age range 15-69) by province (compared with official clinically-confirmed COVID-19 case rates in mid-January 2021) are: EC-63%(2.8%), NC-32%(2.2%), FS-46%(2.4%), and ZN-52%(2.4%). Conclusions: Our study demonstrates substantial differences in dissemination of SARS-CoV-2 infection between different race groups, most likely explained by historically based differences in socio-economic status and housing conditions. As has been seen in other areas, even such high seroprevalence does not guarantee population-level immunity against new outbreaks - probably due to viral evolution and waning of antibody neutralization. Despite its limitations, notably a 'healthy donor' effect, it seems plausible that these estimates are reasonably generalisable to actual population level anti-SARS-CoV-2 seroprevalence, but should be further verified.