Introduction
The ongoing global effort to vaccinate an estimated 60% of the human population started in December 2020. In just six months, mass vaccine campaigns have seen approximately 5 billion doses of COVID19 vaccines administered and more than a quarter of the world population having received at least one dose (1). There are currently 13 different vaccines in use, with three major emergency authorised platforms including: inactivated SARsCoV2 virus (Sinopharm and Sinovac-CoronaVac); adenoviral-vectored (ChadOx/AstraZeneca and Ad26.COV2.S); and the mRNA vaccines (Moderna mRNA 1273 and Pfizer/BionNtech Comirnaty) – the latter two technologies with either little or no prior large scale human use in other infections. The mass use of these novel vaccine technologies has meant increased reporting of uncommon and rare adverse events following immunisation (AEFI), including immune-mediated events such as Guillain-Barré syndrome and anaphylaxis (2). Large cohort studies such as Sisonke, a phase 3B study of the Ad26.COV2.S in South African (SA) Healthcare workers (HCW), are thus invaluable to provide more detailed information about these uncommon adverse events of special interest (AESI).
Allergic AEFI are well-known and reported with almost all registered vaccines, with the prevalence of anaphylaxis in most vaccine safety surveillance systems ~1 in a million doses (3, 4). Soon after the emergency authorisation of mRNA COVID19 vaccines an increased prevalence of anaphylaxis was noted with this novel platform, with prevalence estimates from 2-100 per million doses (2, 5, 6), and self-reported allergic reactions in ~2% of vaccine recipients (2). Few reports of anaphylaxis following ChAdOx1-S adenovirus vaccine are available, with prevalence estimates of 0.3-33 per million doses (5). No anaphylactic events occurred in the ENSEMBLE trials of the Ad26.COV2.S (7, 8), with only one post-marketing surveillance study reported to date(9). There are several reports of self-limiting, delayed, large local allergic reactions surrounding the injection site following the Moderna mRNA 1273 vaccine (10), but the prevalence, spectrum and outcomes of delayed allergic reactions to other COVID19 vaccines have not been reported. Thus, we aimed to detail the spectrum of immediate and delayed allergic AEFI reported following Ad26.COV2.S vaccination in a large cohort of SA HCWs.