Safety evaluation of the single-dose Ad26. COV2.S vaccine among healthcare workers in the Sisonke study in South Africa : a phase 3b implementation trial

Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data.Funding for the Sisonke Study was provided by: The National Department of Health through baseline funding to the South African Medical Research Council; the Solidarity Response Fund NPC; The Michael & Susan Dell Foundation; the ELMA Vaccines and Immunization Foundation; the ELMA Vaccines and Immunization Foundation; and the Bill & Melinda Gates Foundation.https://journals.plos.org/plosmedicinedm2022Paediatrics and Child HealthSchool of Health Systems and Public Health (SHSPH

Safety evaluation of the single-dose Ad26.COV2.S vaccine among healthcare workers in the Sisonke study in South Africa: A phase 3b implementation trial

Background Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data. Methods and findings In this open-label phase 3b implementation study among all eligible HCWs in South Africa registered in the national Electronic Vaccination Data System (EVDS), we monitored adverse events (AEs) at vaccination sites through self-reporting triggered by text messages after vaccination, healthcare provider reports, and active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from the day of first vaccination (17 February 2021) until 28 days after the final vaccination in the study (15 June 2021). COVID-19 breakthrough infections, hospitalisations, and deaths were ascertained via linkage of the electronic vaccination register with existing national databases. Among 477,234 participants, 10,279 AEs were reported, of which 138 (1.3%) were serious AEs (SAEs) or AEs of special interest. Women reported more AEs than men (2.3% versus 1.6%). AE reports decreased with increasing age (3.2% for age 18–30 years, 2.1% for age 31–45 years, 1.8% for age 46–55 years, and 1.5% for age &gt; 55 years). Participants with previous COVID-19 infection reported slightly more AEs (2.6% versus 2.1%). The most common reactogenicity events were headache (n = 4,923) and body aches (n = 4,483), followed by injection site pain (n = 2,767) and fever (n = 2,731), and most occurred within 48 hours of vaccination. Two cases of thrombosis with thrombocytopenia syndrome and 4 cases of Guillain-Barré Syndrome were reported post-vaccination. Most SAEs and AEs of special interest (n = 138) occurred at lower than the expected population rates. Vascular (n = 37; 39.1/100,000 person-years) and nervous system disorders (n = 31; 31.7/100,000 person-years), immune system disorders (n = 24; 24.3/100,000 person-years), and infections and infestations (n = 19; 20.1/100,000 person-years) were the most common reported SAE categories. A limitation of the study was the single-arm design, with limited routinely collected morbidity comparator data in the study setting. Conclusions We observed similar patterns of AEs as in phase 3 trials. AEs were mostly expected reactogenicity signs and symptoms. Furthermore, most SAEs occurred below expected rates. The single-dose Ad26.COV2.S vaccine demonstrated an acceptable safety profile, supporting the continued use of this vaccine in this setting. Trial registration ClinicalTrials.gov NCT04838795; Pan African Clinical Trials Registry PACTR202102855526180. </jats:sec

Safety of the single-dose Ad26.CoV2.S vaccine among healthcare workers in the phase 3b Sisonke study in South Africa

ABSTRACTBackgroundThe Sisonke open-label phase 3b implementation study aimed to assess the safety and effectiveness of the Janssen Ad26.CoV2.S vaccine among health care workers (HCWs) in South Africa. Here, we present the safety data.MethodsWe monitored adverse events (AEs) at vaccination sites, through self-reporting triggered by text messages after vaccination, health care provider reports and by active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from day of first vaccination (17 February 2021) until 28 days after the final vaccination (15 June 2021). COVID-19 breakthrough infections, hospitalisations and deaths were ascertained via linkage of the electronic vaccination register with existing national databases.FindingsOf 477,234 participants, 10,279 (2.2%) reported AEs, of which 139 (1.4%) were serious. Women reported more AEs than men (2.3% vs. 1.6%). AE reports decreased with increasing age (3.2% for 18–30, 2.1% for 31-45, 1.8% for 46-55 and 1.5% in &gt;55-year-olds). Participants with previous COVID-19 infection reported slightly more AEs (2.6% vs. 2.1%). The commonest reactogenicity events were headache and body aches, followed by injection site pain and fever, and most occurred within 48 hours of vaccination. Two cases of Thrombosis with Thrombocytopenia Syndrome and four cases of Guillain-Barre Syndrome were reported post-vaccination. Serious AEs and AEs of special interest including vascular and nervous system events, immune system disorders and deaths occurred at lower than the expected population rates.InterpretationThe single-dose Ad26.CoV2.S vaccine had an acceptable safety profile supporting the continued use of this vaccine in our setting.FundingFunding was provided by the National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael &amp; Susan Dell Foundation, The Elma Vaccines and Immunization Foundation - Grant number 21-V0001, and the Bill &amp; Melinda Gates Foundation – grant number INV-030342.</jats:sec

Sisonke study statistical analysis plan.

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CONSORT checklist.

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Observed versus expected (O/E) analysis of selected serious adverse events.

Observed versus expected (O/E) analysis of selected serious adverse events.</p

Sisonke study protocol.

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Observed versus expected analysis of selected serious adverse events within 28 days of vaccination.

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High Asymptomatic Carriage With the Omicron Variant in South Africa

We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with human immunodeficiency virus (HIV) strongly correlated with increased odds of being SARS-CoV-2 polymerase chain reaction (PCR) positive