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.

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.

Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial).

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

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.

Rapid and Successful Implementation of a COVID-19 Convalescent Plasma Programme-The South African Experience.

BACKGROUND: COVID-19 convalescent plasma (CCP) has been considered internationally as a treatment option for COVID-19. CCP refers to plasma collected from donors who have recovered from and made antibodies to SARS-CoV-2. To date, convalescent plasma has not been collected in South Africa. As other investigational therapies and vaccination were not widely accessible, there was an urgent need to implement a CCP manufacture programme to service South Africans. METHODS: The South African National Blood Service and the Western Cape Blood Service implemented a CCP programme that included CCP collection, processing, testing and storage. CCP units were tested for SARS-CoV-2 Spike ELISA and neutralising antibodies and routine blood transfusion parameters. CCP units from previously pregnant females were tested for anti-HLA and anti-HNA antibodies. RESULTS: A total of 987 CCP units were collected from 243 donors, with a median of three donations per donor. Half of the CCP units had neutralising antibody titres of >1:160. One CCP unit was positive on the TPHA serology. All CCP units tested for anti-HLA antibodies were positive. CONCLUSION: Within three months of the first COVID-19 diagnosis in South Africa, a fully operational CCP programme was set up across South Africa. The infrastructure and skills implemented will likely benefit South Africans in this and future pandemics.