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.

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.

Reassessment of hepatitis B virus window periods for two transcription-mediated amplification assays using screening data of South African blood donors.

BACKGROUND: Transcription-mediated amplification assays for HBV DNA detection have transitioned from the Ultrio to the Ultrio Plus assay, which features increased analytic sensitivity due to inclusion of a target enhancer reagent. The impact on HBV detection for different categories of HBV infection has not been fully evaluated. STUDY DESIGN AND METHODS: Hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) detection rates as well as viral load (VL) distributions in HBV nucleic acid test (NAT)-yield samples were compared during 1 year of screening of South African blood donors with the Ultrio assay and the subsequent year by the Ultrio Plus version. HBV-DNA concentration at the HBsAg seroconversion point was established by regression analysis using a set of antibody to hepatitis B core antigen-negative acute viremic samples. RESULTS: Ultrio Plus detected twofold more window-period (WP) NAT yield donations and 1.7-fold more occult HBV infections than Ultrio. The VL distribution data indicated that Ultrio not only missed samples of less than 100 copies/mL, but also a substantial number higher than this level. The VL at the HBsAg seroconversion point was estimated at 916 copies/mL, whereas the VL at the NAT-conversion points was calculated at 63 and 4.1 copies/mL for Ultrio and Ultrio Plus. This reduced the infectious WP (compared to HBsAg testing) by 10.3 and 20.4 days, respectively. CONCLUSION: The higher-than-expected increase in HBV-NAT yields after introduction of the Ultrio Plus assay is likely attributable to variable sensitivity of the former Ultrio assay for different HBV samples. Therefore, previously published HBV WP reduction and residual risk estimates based on analytical sensitivity of the Ultrio assay need to be revised.

Health economic implications of testing blood donors in South Africa for HTLV 1 & 2 infection.

BACKGROUND AND OBJECTIVES: Currently, HTLV screening is not performed in South Africa (SA). This report describes an economic assessment (budget impact and cost-effectiveness) of implementing different HTLV screening strategies. METHODS: A modified version of the Alliance of Blood Operators risk-based decision-making framework was used to assess the risk and consequences of HTLV in the blood supply in SA. We developed a deterministic model of the cost and consequences of four screening strategies: none, universal, all donors once and first time donors only assuming a transfusion-transmission (TT) efficiency of 10% and a manifestation of clinical disease of 6%. RESULTS: Unscreened blood results in 3·55 symptomatic TT-HTLV cases and a total healthcare cost of Rand (R)3 446 950 (US Dollars (USD)229 800) annually. Universal screening would cost R24 000 000 (USD1 600 000) per annum and prevent 3·54 (99·8%) symptomatic TT-HTLV cases in the first year and 0·55 (98·4%) symptomatic TT-HTLV cases in the second year at a cost per TT-HTLV prevented of R6 780 000 (USD450 000) in year one and R43 254 000 (USD2 890 000) in year two. Screening all donors once would cost R16,200,000 (USD1 080 000) or R4 600 000 (USD306 000) per symptomatic TT-HTLV infection prevented in year one. Total costs decrease to R5 100 000 (USD340 000) in year 2 but the cost per TT-HTLV prevented increases to R10 700 000 (USD713 333). CONCLUSION: This analysis contributed to the decision not to implement HTLV screening as the healthcare budget and particularly the budget for blood transfusion in SA is insufficient to provide appropriate treatment. Arguably, available resources can be more efficiently utilized in other healthcare programs.

The prevalence of human T-lymphotropic virus type 1 & 2 (HTLV-1/2) in South African blood donors.

BACKGROUND AND OBJECTIVES: Donated blood is not currently screened for human T-cell lymphotropic virus (HTLV) in South Africa. Several small studies have detected HTLV-1 in South Africa, but prevalence by geographic region or population group is unavailable. MATERIALS AND METHODS: We performed a large seroprevalence study of South African blood donors during 3 months in 2013. All geographic regions except the Western Cape were included, and Black and Coloured (local term for mixed race) donors were oversampled. Identity-unlinked plasma samples were screened with the Abbott Prism HTLV-1/2 assay, and repeatedly reactive samples were tested by the Inno-LIA HTLV-1/2 Score confirmatory assay. Odds ratios were calculated with multivariable logistic regression. RESULTS: Of 46 752 donors tested, 133 (0·28%) were initially reactive, 111 (0·24%) repeatedly reactive and 57 (0·12%) confirmed positive for HTLV-1; none were HTLV-2 positive. Prevalence was 0·062% weighted to annual blood donations but highly concentrated in the Black population group (OR = 20·24 CI: 2·77-147·88); higher in females than males (OR = 1·81 CI: 1·06-3·08); and in donors aged >50 years compared to ages 16-19 (OR = 6·4 CI: 2·95-13·86). After controlling for age, sex and population group, there was no difference in prevalence between new and repeat blood donors or among geographic regions within South Africa. CONCLUSIONS: We conclude that HTLV-1 infection is widespread among the Black population of South Africa and its epidemiology is similar to other endemic areas. Because South Africa is increasing its recruitment of Black blood donors, the implications for blood screening require further consideration.

Discovery of False Elite Controllers: HIV Antibody-Positive RNA-Negative Blood Donors Found To Be on Antiretroviral Therapy.

BACKGROUND: An increase in potential HIV elite controllers (EC) and anecdotal reports of antiretroviral therapy (ART) use among South African blood donors led us to verify EC status. METHODS: Stored plasma samples from potential EC were tested for ART drugs. Demographic and temporal associations were examined using multivariable logistic regression. RESULTS: Of 226 potential EC, 150 (66.4%) had detectable ART with increasing prevalence by year (OR = 7.57 for 2016 vs 2010, 95% confidence interval, 1.96-32.17). DISCUSSION: False presumptive EC status due to undisclosed ART represents a growing proportion of potential EC donors in South Africa coincident with the country's ART rollout.

Assessment of HIV transfusion transmission risk in South Africa: a 10-year analysis following implementation of individual donation nucleic acid amplification technology testing and donor demographics eligibility changes.

BACKGROUND: In 1998 we estimated that 34/million infectious window period donations were entering the blood supply at the South African National Blood Service. Selective use of donations based on donor race-ethnicity reduced this risk to 26/million donations but was deemed unethical. Consequently, in 2005 South African National Blood Service eliminated race-ethnicity-based collection policies and implemented individual-donation nucleic acid testing (ID-NAT). We describe the change in donor base demographics, human immunodeficiency virus (HIV) detection rates, and transfusion-transmissible HIV risk. STUDY DESIGN AND METHODS: In ten years 7.7 million donations were tested for anti-HIV and HIV RNA. Number of donations, HIV prevalence, ID-NAT yield rate, serology yield rate and residual transfusion-transmissible HIV risk were analyzed by donor type, race-ethnicity, age, and sex. Multiple regression analysis was performed to investigate the determinants of HIV-positive and nucleic acid testing yield donations. RESULTS: The combined strategy of increasing donations from black donors and implementing ID-NAT increased the proportion of donations from black donors from 6% in 2005 to 30% in 2015 (p < 0.00001), and reduced the transfusion-transmissible risk from 24 to 13 per million transfusions. ID-NAT interdicted 481 (1:16,100) seronegative window period donations, while one transfusion-transmissible case (0.13 per million) was documented. Race-ethnicity and donor type were highly significant predictors of HIV positivity, with adjusted odds ratio for first-time donors of 12.5 (95% confidence interval, 11.9-13.1) and for black race-ethnicity of 31.1 (95% confidence interval, 28.9-33.4). The proportion of serology yields among HIV-infected donors increased from 0.27% to 2.4%. CONCLUSION: ID-NAT enabled the South African National Blood Service to increase the number of donations from black donors fivefold while enhancing the safety of the blood supply.

Impact of individual-donation nucleic acid testing on risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission by blood transfusion in South Africa.

BACKGROUND: In 2005, the South African National Blood Service introduced individual-donation (ID) nucleic acid test (NAT) screening for human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, and hepatitis B virus (HBV) DNA. At the same time the use of ethnic origin to prioritize the transfusion of blood according to a hierarchy of residual risk was discontinued. STUDY DESIGN AND METHODS: ID-NAT (Ultrio on Procleix Tigris, Chiron) and serology (PRISM, Abbott) repeat test and confirmation testing algorithms were designed to enable differentiation between false-positive and true-NAT and -serology yields. After 1 year, the NAT and serology yield rates in first-time, lapsed, and repeat donors were analyzed and used to estimate the residual risk of HIV, HBV, and HCV infections by blood transfusion. RESULTS: The HIV, HBV, and HCV ID-NAT window phase yield rates in 732,250 blood donations were 1:45,765, 1:11,810, and 1:732,200, respectively. Seven of 16 HIV window phase donations with viral loads above 16,000 copies/mL were HIV p24 antigen enzyme-linked immunosorbent assay positive. PRISM detected anti-HIV and hepatitis B surface antigen (HBsAg) in 89.4 and 73.9% of early infections in repeat donors. The Procleix assay detected viremia in 99.7 and 95.5% of anti-HIV- and HBsAg-positive first-time donors. In these donors, the occult HBV DNA carrier rate was 1:5200. The residual transmission risk of ID-NAT HIV, HBV, and HCV window phase donations was estimated at 1:479,000, 1:61,500, and 1:21,000,000 respectively. CONCLUSION: One-year ID-NAT screening of 732,250 donations interdicted 16 HIV, 20 HBV, and 1 HCV window phase donations and 42 anti-hepatitis B core antigen-reactive infections during an early recovery or a later stage of occult HBV infection.