Trends in Covid-19 Admissions and Deaths among People with Hiv in South Africa

Background: South Africa experienced five COVID-19 waves and over 90% of the population have developed immunity. HIV prevalence among adults is 19% and over 2 million people have uncontrolled viral loads, posing a risk for poor COVID-19 outcomes. Using national hospital surveillance data, we aimed to investigate trends in admission and factors associated with in-hospital COVID-19 mortality among people with HIV (PWH) in South Africa. Method(s): Data between March 5, 2020 and May 28, 2022 from the national COVID-19 hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. A wave was defined as the period for which weekly incidence was >=30 cases/100,000 people. Descriptive statistics were employed for admissions and mortality trends. Postimputation random effect multivariable logistic regression models compared (a) characteristics of PWH and HIV-uninfected individuals, and (b) factors associated with mortality among PWH. Result(s): 68.7% (272,287/396,328) of COVID-19 admissions had a documented HIV status. PWH accounted for 8.4% (22,978/272,287) of total admissions, and 9.8%, 8.0%, 6.8%, 12.2% and 6.7% of admissions in the D614G, Beta, Delta, Omicron BA.1 and Omicron BA.4/BA.5 waves respectively. The case fatality ratio (CFR) among PWH and HIV-uninfected was 24.3% (5,584/22,978) vs 21.7% (54,110/249,309) overall, and in the respective waves was 23.7% vs 20.4% (D614G), 27.9% vs 26.6% (Beta), 26.2% vs 24.5% (Delta), 18.2% vs 9.1% (Omicron BA.1) and 16.8% vs 5.5% (Omicron BA.4/BA.5). Chronic renal disease, malignancy and past TB were more likely, and hypertension and diabetes were less likely in PWH compared to HIV-uninfected individuals. Among PWH, along with older age, male sex and presence of a comorbidity, there was a lower odds of mortality among individuals with prior SARS-CoV-2 infection (aOR 0.6;95% CI 0.4-0.8);>=1 dose vaccination (aOR 0.1;95% CI 0.1-0.1);and those admitted in the Delta (aOR 0.9;95% CI 0.8-0.9), Omicron BA.1 (aOR 0.5;95% CI 0.5-0.6) and Omicron BA.4/BA.5 (aOR 0.5;95% CI 0.4-0.7) waves compared to the D614G wave. PWH with CD4< 200 had higher odds of in-hospital mortality (aOR 1.9;95% CI 1.8-2.1). Conclusion(s): In South Africa, mortality among PWH was less likely in the Delta and Omicron waves but PWH had a disproportionate burden of mortality during the two Omicron waves. Prior immunity protected against mortality, emphasizing the importance of COVID-19 vaccination among PWH, particularly PWH with immunosuppression.

Heterologous vaccination of BNT162b2 in Ad26. COV2.S-vaccinated healthcare workers elicits long-term humoral immune response

Background. To date, there are no immunological data for the SARS-CoV-2 heterologous vaccination schedule in the South African (SA) population. Objectives. To assess and compare the immunogenicity and reactogenicity of the Jansen Ad26.COV2.S vaccine with the Pfizer/BioNTechBNT162b2 booster following prime Ad26.COV2.S in 65 SA healthcare workers. Methods. In a prospective, quantitative, cross-sectional trial on individuals >18 years of age vaccinated with a single Ad26.COV2.S dose or single Ad26.COV2.S and a BNT162b2 single-dose/both doses booster, participants filled in a questionnaire on their demographics, type of vaccination, breakthrough infection/s (BTI/s), vaccine reactogenicity, prior SARS-CoV-2 infection and dates of vaccination. Qualitative analysis for presence/absence of anti-S (spike) immunoglobulin G (IgG) was performed using the Euroimmun anti-IgG enzyme-linked immunoassay kit, and anti-S IgG titres were quantitatively assessed using the Abbott IgG Quant II kit. Results. Between 28 October 2021 and 30 November 2021, 65 individuals were enrolled and assigned as either prime Ad26.COV2.S (n=18) or Ad26.COV2.S with a BNT162b2 supplement (n=47) at Charlotte Maxeke Johannesburg Academic Hospital, SA (mean age 45 years (95% confidence interval (CI) 29.5 - 58), 42 women (64.6%) and 23 men (35.4%)). The median IgG titre for the primed Ad26.COV2.S group was 4 272.55 (95% CI 68.40 - 10 351.40) and that for the BNT162b2 supplement group was 7 360.80 (95% CI 4 207.40 - 15 372.60). In the univariate model, the BNT162b2 supplement group showed a significant 1.99 times higher antibody titre factor (95% CI 0.045 - 5.553;p<0.005) than the Ad26.COV2.S group. In both univariate and multivariate models, age, time since prime vaccination, BTI and prior infection failed to show any statistically significant association (p>0.05) with antibody titres in both groups. However, sex (-55.381 (95% CI -76.984 - -13.498;p=0.018) in a multivariate model was found to have a statistically significant association with anti-S IgG titres observed in both groups. Participants who received their first dose of BNT162b2 9 - 10 months after their prime Ad26.COV2.S (n=44) had a higher degree of antibody response than those who received it earlier. Reactogenicity was observed to be manageable, with mild/moderate adverse effects in the study population. Conclusion. A BNT162b2 supplement given in single or two doses as booster in individuals primed with Ad26.COV2.S induced immunological response, with acceptable and manageable reactogenicity. This study provides novel evidence of the highest degree of antibody response in individuals who received a BNT162b2 first dose 9 - 10 months after prime Ad26.COV2.S, implying that a longer time gap between the two vaccines stimulates higher antibody response than a shorter gap, and that this antibody response can persist for as long as 6 months after the last BNT162b2 dose. Copyright © 2022 South African Medical Association. All rights reserved.

Recovery and transforming the South African health system

The COVID-19 pandemic has devastated lives and livelihoods globally and in South Africa (SA). The SA government has been lauded for its swift response to the pandemic, in March 2020 and subsequently. Many routinely provided health services were severely disrupted and there is an urgent need to recover to 2019 levels at least. In this paper, the lessons from the COVID-19 response are discussed and proposals for transformation of the SA health system are considered.

SAFETY and EFFECTIVENESS of the Ad26.COV2.S VACCINE in SOUTH AFRICA

Background: The Sisonke Phase IIIB open-label implementation study vaccinated health care workers (HCWs) with the single dose Ad26.COV2.S vaccine during two phases of the South African Covid-19 epidemic, dominated first by the Beta followed by the Delta variant of concern. Methods: HCWs were vaccinated over 3 months (17 February-17 May 2021). Safety was monitored by self-reporting, facility reporting and linkage to national databases. Vaccine effectiveness (VE) against Covid-19 related hospitalisation, hospitalisation requiring critical or intensive care and death, ascertained 28 days or more post vaccination was assessed up until 17 July 2021. Nested sub-cohorts (A and B) from two national medical schemes were evaluated to assess VE using a matched retrospective cohort design. Results: Over the 3-month period, 477234 HCWs were vaccinated in 122 vaccination sites across South Africa. VE derived from the sub-cohorts comprising 215 813 HCWs was 83% (95% CI 75-89) to prevent Covid-19 deaths, 75% (95% CI 69-82) to prevent hospital admissions requiring critical or intensive care and 67% (95% CI 62-71) to prevent Covid-19 related hospitalisations. The VE was maintained in older HCWs and those with comorbidities including HIV infection. VE remained consistent throughout the Beta and Delta dominant phases of the study. 10279 adverse events were reported and 139 (1.4%) were serious, including two cases of thrombosis with thrombocytopenia syndrome and four cases of Guillain-Barré syndrome who recovered. Conclusion: The single dose Ad26.COV2.S was safe and effective against severe Covid-19 disease and death post-vaccination, and against both Beta and Delta variants providing real-world evidence for its use globally.

Guiding equitable prioritisation of COVID-19 vaccine distribution and strategic deployment in South Africa to enhance effectiveness and access to vulnerable communities and prevent waste

Background. In South Africa (SA), >2.4 million cases of COVID-19 and >72 000 deaths were recorded between March 2020 and 1 August 2021, affecting the country's 52 districts to various extents. SA has committed to a COVID-19 vaccine roll-out in three phases, prioritising frontline workers, the elderly, people with comorbidities and essential workers. However, additional actions will be necessary to support efficient allocation and equitable access for vulnerable, access-constrained communities. Objectives. To explore various determinants of disease severity, resurgence risk and accessibility in order to aid an equitable, effective vaccine roll-out for SA that would maximise COVID-19 epidemic control by reducing the number of COVID-19 transmissions and resultant deaths, while at the same time reducing the risk of vaccine wastage. Methods. For the 52 districts of SA, 26 COVID-19 indicators such as hospital admissions, deaths in hospital and mobility were ranked and hierarchically clustered with cases to identify which indicators can be used as indicators for severity or resurgence risk. Districts were then ranked using the estimated COVID-19 severity and resurgence risk to assist with prioritisation of vaccine roll-out. Urban and rural accessibility were also explored as factors that could limit vaccine roll-out in hard-to-reach communities. Results. Highly populated urban districts showed the most cases. Districts such as Buffalo City, City of Cape Town and Nelson Mandela Bay experienced very severe first and second waves of the pandemic. Districts with high mobility, population size and density were found to be at highest risk of resurgence. In terms of accessibility, we found that 47.2% of the population are within 5 km of a hospital with 50 beds, and this percentage ranged from 87.0% in City of Cape Town to 0% in Namakwa district. Conclusions. The end goal is to provide equal distribution of vaccines proportional to district populations, which will provide fair protection. Districts with a high risk of resurgence and severity should be prioritised for vaccine roll-out, particularly the major metropolitan areas. We provide recommendations for allocations of different vaccine types for each district that consider levels of access, numbers of doses and cold-chain storage capability.

Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID-19, including hospitalisations and deaths. The Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies: (i) consistently advocate for vaccination to reduce public hesitancy;(ii) an electronic vaccination data system (EVDS) is critical;(iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres;(iv) let digitally literate people help elderly and marginalised people to register for vaccination;(v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators;(vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres;(vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks;(viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system;(ix) develop efficient systems to monitor and investigate COVID-19 breakthrough infections;and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics.

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID­19, including hospitalisations and deaths. The  Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID­19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Guiding equitable prioritisation of COVID-19 vaccine distribution and strategic deployment in South Africa to enhance effectiveness and access to vulnerable communities and prevent waste.

BACKGROUND: In South Africa (SA), >2.4 million cases of COVID­19 and >72 000 deaths were recorded between March 2020 and 1 August 2021, affecting the country's 52 districts to various extents. SA has committed to a COVID­19 vaccine roll-out in three phases, prioritising frontline workers, the elderly, people with comorbidities and essential workers. However, additional actions will be necessary to support efficient allocation and equitable access for vulnerable, access-constrained communities. OBJECTIVES: To explore various determinants of disease severity, resurgence risk and accessibility in order to aid an equitable, effective vaccine roll-out for SA that would maximise COVID­19 epidemic control by reducing the number of COVID­19 transmissions and resultant deaths, while at the same time reducing the risk of vaccine wastage. METHODS: For the 52 districts of SA, 26 COVID­19 indicators such as hospital admissions, deaths in hospital and mobility were ranked and hierarchically clustered with cases to identify which indicators can be used as indicators for severity or resurgence risk. Districts were then ranked using the estimated COVID­19 severity and resurgence risk to assist with prioritisation of vaccine roll-out. Urban and rural accessibility were also explored as factors that could limit vaccine roll-out in hard-to-reach communities. RESULTS: Highly populated urban districts showed the most cases. Districts such as Buffalo City, City of Cape Town and Nelson Mandela Bay experienced very severe first and second waves of the pandemic. Districts with high mobility, population size and density were found to be at highest risk of resurgence. In terms of accessibility, we found that 47.2% of the population are within 5 km of a hospital with ≥50 beds, and this percentage ranged from 87.0% in City of Cape Town to 0% in Namakwa district. CONCLUSIONS: The end goal is to provide equal distribution of vaccines proportional to district populations, which will provide fair protection. Districts with a high risk of resurgence and severity should be prioritised for vaccine roll-out, particularly the major metropolitan areas. We provide recommendations for allocations of different vaccine types for each district that consider levels of access, numbers of doses and cold-chain storage capability.

Validation of roche immunoassay for severe acute respiratory coronavirus 2 in South Africa

Background: Serology testing is an important ancillary diagnostic to the reverse transcriptase polymerase chain reaction (RT-PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the performance of the Roche Elecsys™ chemiluminescent immunoassay (Rotkreuz, Switzerland), that detects antibodies against the SARS-CoV-2 nucleocapsid antigen, at an academic laboratory in South Africa. Methods: Serum samples were collected from 312 donors with confirmed positive SARS-CoV-2 RT-PCR tests, with approval from a large university’s human research ethics committee. Negative controls included samples stored prior to December 2019 and from patients who tested negative for SARS-CoV-2 on RT-PCR and were confirmed negative using multiple serology methods (n = 124). Samples were stored at –80 °C and analysed on a Roche cobas™ 602 autoanalyser. Results: Compared with RT-PCR, our evaluation revealed a specificity of 100% and overall sensitivity of 65.1%. The sensitivity in individuals > 14 days’ post-diagnosis was 72.6%, with the highest sensitivity 31–50 days’ post-diagnosis at 88.6%. Results were also compared with in-house serology tests that showed high agreement in majority of categories. Conclusions: The sensitivity at all-time points post-diagnosis was lower than reported in other studies, but sensitivity in appropriate cohorts approached 90% with a high specificity. The lower sensitivity at earlier time points or in individuals without symptomatology may indicate failure to produce antibodies, which was further supported by the comparison against in-house serology tests.

The role of serological testing in the SARS-CoV-2 outbreak.

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies.