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

Abstract

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 > 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. Saimbarashe Takuva, Azwi Takalani, and colleagues investigate the frequency and incidence of adverse events reported after receipt of a single dose of the Ad26.COV2.S COVID-19 vaccine among health care workers in South Africa. Author summary Why was this study done? While the safety of the Ad26.COV2.S vaccine was established in phase 3 clinical trials, continuous evaluation of safety in expanded populations is crucial. The Sisonke phase 3b implementation study enrolled almost half a million healthcare workers, providing an opportunity to further evaluate the safety of the single-dose Ad26.COV2.S vaccine. What did the researchers do and find? A total of 477,234 healthcare workers across all South African provinces received the Ad26.COV2.S vaccine between 17 February 2021 and 17 May 2021. Through self-reports and active case finding, adverse events, serious adverse events, and adverse events of special interest were identified. Overall occurrence of adverse events was low. The majority of adverse events reported were common reactogenicity signs and symptoms. Most serious adverse events and adverse events of special interest, including vascular events, immune system disorders, and deaths, occurred at lower than the expected population rates. What do these findings mean? The single-dose Ad26.COV2.S vaccine had an acceptable safety profile. This supports continued use of this vaccine in large rollout programmes.