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
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Abstract
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 .
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SciScore for 10.1101/2021.12.20.21267967: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All eligible HCWs, who registered on the national Electronic Vaccination Data System (EVDS) and provided electronic consent for the study, were eligible for enrolment.
IRB: The institutional health research ethics committees of participating clinical research sites approved the study, which was overseen by the South African Health Products Regulatory Authority (Ref: 20200465)Sex as a biological variable Pregnant and breastfeeding women were excluded due to a lack of sufficient safety data at that time. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources All statistical analyses were conducted using STATA … SciScore for 10.1101/2021.12.20.21267967: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All eligible HCWs, who registered on the national Electronic Vaccination Data System (EVDS) and provided electronic consent for the study, were eligible for enrolment.
IRB: The institutional health research ethics committees of participating clinical research sites approved the study, which was overseen by the South African Health Products Regulatory Authority (Ref: 20200465)Sex as a biological variable Pregnant and breastfeeding women were excluded due to a lack of sufficient safety data at that time. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources All statistical analyses were conducted using STATA version 14 (STATA Corp., College Station, TX, USA). STATAsuggested: (Stata, RRID:SCR_012763)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The Sisonke study had several limitations. Firstly, the surveillance system was primarily passive relying on self-reporting, thus some AEs may have gone unreported. It is likely that the system was better suited to detect SAEs than milder AEs, which participants may have ignored rather than reported. As active contact with participants was up to two-weeks post-vaccination, it is probable that SAEs other than deaths and COVID-19 events were more likely to be reported during this period leading to underestimation of SAEs which occurred. The active linkage of the unique identifier in EVDS with the deaths on the national population registry and COVID-19 laboratory system ensured identification of nearly all possible deaths and COVID-19 events in the study. Additionally, considering the large number of participants in the study, not all self-reported AEs could be verified and only SAEs and AEs of medical concern were investigated further. Interpretation of the disproportionality analysis should be cautious given the uncertainties in both the observed and expected event rates, variable follow-up time, non-South African reference data for some groups, and potential differences in age-sex distributions between Sisonke and reference data. However, while disproportionality analysis in the context of safety signal detection is mainly exploratory, it has the utility to identify potentially important associations between AE and vaccine. In this study, the analysis confirmed current report...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04838795 Recruiting Sisonke (Together): OPEN LABEL TRIAL COVID-19 Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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