Methods
The Sisonke (“Together” in isiZulu) phase 3B study is an
open-label, single-arm implementation study of the Ad26.COV2.S COVID19
vaccine among adult (>18 years) HCWs in SA. The trial is
sponsored by the SA Medical Research Council (SAMRC) with vaccines
provided by Janssen Vaccines & Prevention B.V, a pharmaceutical company
of Johnson & Johnson (NCT04838795)
(http://sisonkestudy.samrc.ac.za/). The Institutional Review
Boards/Ethics Committees of participating Clinical Research Sites
approved the study, which was conducted under the oversight of the South
African Health Products Regulatory Authority (SAHPRA).
Vaccinations were conducted in collaboration with the routine Provincial
Department of Health public and private vaccination centres across all
nine provinces of SA and overseen by Good Clinical Practice
(GCP)-trained personnel linked to each of the ENSEMBLE trial research
sites. Participants underwent informed consent before receiving a single
intramuscular (IM) injection of Ad26.COV2.S at a dose level of
5×1010 virus particles. Participants with a previous
history of allergic reactions to vaccinations were observed for 30
minutes post-vaccination whereas the rest of the participants were
observed for 15 minutes post-vaccination.
Safety monitoring was conducted through a combination of passive
reporting and active case finding. An electronic adverse event reporting
link was sent via text message on days 1, 7 and 14 post vaccination.
Adverse events could also be reported either by calling a toll-free
24-hour safety line or through the completion of an adverse event report
form which was available at vaccination sites and hospitals. The safety
team reviewed serious adverse events and adverse events of special
interest reports daily. Full details of the Sisonke pharmacovigilance
and safety reporting processes are detailed elsewhere (11).
The Sisonke safety database was searched for allergic AEFI using a
comprehensive list of possible allergy-related search terms (see
supplementary appendix). Duplicates and clear non-allergic entries were
removed and then all reports were screened by an allergist. In addition
to the initial reporting, telephonic contact was attempted with all
participants reporting a possible allergy AEFI where details were
missing to clarify the event and collect additional information on past
medical and allergy history as well as details of treatment and outcomes
of mild/moderate allergic AEFI requiring treatment and healthcare
contact. Suspected anaphylaxis cases were adjudicated by two physicians
using the Brighton Collaboration and NIAID case definition; with cases
needing to meet both definitions to be considered confirmed cases
(12-14). Immediate reactions were restricted to those occurring within 6
hours post vaccination (15).
Descriptive statistics were performed using counts and proportions for
categorical data, and medians and interquartile ranges for continuous
variables. All statistical analyses were conducted using STATA version
14 (STATA Corp., College Station, TX, USA).