Efficacy of the AZD1222 (ChAdOx1 nCoV-19) COVID-19 Vaccine Against SARS-CoV-2 Variants of Concern (preprint)

In this South African phase 1/2b study, we demonstrated vaccine efficacy (VE) of two doses of AZD1222 for asymptomatic and symptomatic SARS-CoV-2 infection: 90.6% against wild-type and 77.1% against the Delta variant [≥]9 months after vaccination. VE against infection with the Beta variant, which preceded circulation of Delta, was 6.7%. Clinical trial identifierCT.gov NCT04444674

ChAdOx1 nCoV-19 (AZD1222) Vaccine in People Living With and Without HIV (preprint)

Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern1. People living with HIV (PLWH) are at increased risk for adverse COVID-19 outcomes compared with HIV-negative individuals2-5, and are a high-risk group for COVID-19 prevention4. The ChAdOx1 nCoV-19 (AZD1222) vaccine has demonstrated safety and efficacy against COVID-19 in clinical trials6-8. To date, there are no reports on the safety and immunogenicity of this, or any COVID-19 vaccine, in PLWH, and reports on the immunogenicity of COVID-19 vaccines in Africa are limited9. Here, we show comparable safety and immunogenicity of two doses of ChAdOx1 nCoV-19 between PLWH and HIV-negative individuals in South Africa. Furthermore, in PLWH previously exposed to SARS-CoV-2, antibody responses increased substantially from baseline following a priming dose, with modest increases after a booster dose. Full-length spike and receptor-binding domain IgG geometric mean concentrations after a single dose of ChAdOx1 nCoV-19 in PLWH previously exposed to SARS-CoV-2 were 6.49–6.84-fold higher than after two doses in those who were SARS-CoV-2 naïve at enrollment. Neutralizing antibody responses were consistent with the antibody-binding responses. This is the first report of a COVID-19 vaccine specific to PLWH, and specific to Africa, and demonstrates favorable safety and immunogenicity of ChAdOx1 nCoV-19 in PLWH.

Preliminary Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant (preprint)

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use. Methods In this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 micrograms recombinant spike protein with 50 micrograms Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy greater than or equal to 7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants. Results A total of 4387 participants were randomized and dosed at least once, 2199 with NVX CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV negative; 6% PLWH), there were 15 and 29 predominantly mild to moderate Covid-19 cases in NVX CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV negative participants was 60.1% (95% CI: 19.9 to 80.1), and did not differ by baseline serostatus. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: -0.6 to 76.2) in HIV-negative participants. Among placebo recipients, the incidence of symptomatic Covid-19 was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX CoV2373; serious adverse events were rare in both groups. Conclusions The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant, while evidence of prior infection with the presumptive original SARS CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)

SARS-CoV-2 Infection Among Healthcare Workers in South Africa: A Longitudinal Cohort Study (preprint)

Background: Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection. We investigated the burden of SARS-CoV-2 infection in a longitudinal cohort of frontline HCWs in South Africa from April to September 2020.Methods: HCWs working in five departments at Chris Hani Baragwanath Academic Hospital were followed-up weekly, independent of clinical symptomatology, during the first wave of the COVID-19 pandemic and tested for SARS-CoV-2 infection by polymerase chain reaction (PCR). Furthermore, paired sera collected at enrolment and end of surveillance were tested for IgG to receptor binding domain of the spike protein to evaluate for sero-response.Findings: Overall 137 (34·6%) of 396 enrolled HCWs had PCR-confirmed SARS-CoV-2 infection (132·1 [95%CI: 111·8, 156·2] per 1,000 person-months), and an additional 27 only showed sero-response at the end of follow-up. HCWs in the Internal Medicine department had the highest rate of SARS-CoV-2 infection (61·7%; 103/167), with HCWs from other departments (27·5%; 63/229) experiencing 70% lower odds of infection (adjust odds ratio 0·29 [95%CI: 0·17, 0·49]) in multivariable analysis. Among SARS-CoV-2 PCR-confirmed cases, 14 (10·4%) HCWs remained asymptomatic, 41 (30·4%) were pre-symptomatic and 80 (59·3%) were symptomatic. Symptomatic cases compared to asymptomatic had lower PCR cycle threshold values at diagnosis (24·2 vs. 28·9) and longer duration of PCR-positivity (18·9 vs. 13·0 days).Interpretation: The high rates of SARS-CoV-2 infection among HCWs in a relatively well-resourced middle-income setting attest to the threat that the COVID-19 pandemic poses to health care systems.Funding: This study was supported by the European & Developing Countries Clinical Trials Partnership (grant number RIA2020EF-3020) and The Bill & Melinda Gates Foundation (grant number INV018148_2020). There was also partial support from the Department of Science and Technology and National Research Foundation: South African Research Chair Initiative in Vaccine Preventable Diseases; and the South African Medical Research Council.Conflict of Interest: MCN has received grant support from the Bill & Melinda Gates Foundation, MedImmune and Pfizer outside the submitted work; has received honoraria from Pfizer and Sanofi Pasteur outside the submitted work. CLC has received grant support from the Bill & Melinda Gates Foundation, Pfizer and IMPRINT outside the submitted work; has received honoraria from Pfizer outside the submitted work. SAM has received grant support from the Bill & Melinda Gates Foundation, Pfizer, GlaxoSmithKline, Minervax and Novavx outside the submitted work; personal fees from Bill & Melinda Gates Foundation outside the submitted work. All other authors have nothing to disclose.Ethical Approval: The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (reference number 200405) and conducted in accordance with Good Clinical Practice guidelines. All study participants provided written informed consent.