Abstract
Adults receiving heterologous COVID-19 immunisation with mRNA (Comirnaty) or adenoviral-vector (Vaxzevria) vaccines had higher reactogenicity rates and sought medical attention more often after two doses than homologous schedules. Reactogenicity was higher among ≤ 50 than > 50 year-olds, women and those with prior symptomatic/confirmed COVID-19. Adults receiving heterologous schedules on clinical advice after severe first-dose reactions had lower reactogenicity after dose 2 following Vaxzevria/Comirnaty (93.4%; 95% confidence interval: 90.5–98.1 vs 48% (41.0–57.7) but not Comirnaty/Vaxzevria (91.7%; (77.5–98.2 vs 75.0% (57.8–87.9).
Highlights
Adults receiving heterologous COVID-19 immunisation with mRNA (Comirnaty) or adenoviral-vector (Vaxzevria) vaccines had higher reactogenicity rates and sought medical attention more often after two doses than homologous schedules
Concerns about vaccine-induced thrombosis and thrombocytopenia syndrome (VITTs) following vaccination with COVID-19 adenoviral vector vaccines has led to several countries recommending an mRNA vaccine for the second dose in younger adults who had been given an adenoviral vector vaccine for their first dose [1,2,3,4]
A clinical trial in England (COMCOV) reported that heterologous schedules using mRNA-based Comirnaty (BNT162b2, BioNTech-Pfizer, Mainz, Germany/New York, United States) hereafter referred to as BNT, and adenovirus vector Vaxrevia (ChAdOx1/nCoV-19, AstraZeneca, Cambridge, United Kingdom), hereafter ChAd, COVID-19 vaccines after a 4-week interval were associated with increased reactogenicity after the booster dose compared with their homologous counterparts, none required hospitalisation [5]
Summary
The most common reason for receiving a heterologous schedule was following clinical advice because of severe reactogenicity after the first dose (290/739, 39.2%). Other reasons for receiving a heterologous schedule included supply issues, individuals requesting a different vaccine, receiving a different vaccine by mistake or other reasons including family history of clotting or recently pregnant In this cohort, too, reactogenicity was higher in those receiving a heterologous compared with homologous schedules (Table 3). 8.1% (106/1,313) individuals overall required medical attention, including 55 who reported requiring medical attention after the first dose, with a higher proportion after a heterologous schedule In those who reporting no, mild or moderate reactions following dose 1, both heterologous cohorts were more likely to report severe symptoms following dose 2: ChAd/ BNT (17.1%; 95% CI: 10.9–24.9) vs ChAd/ChAd (4.3%; 95% CI: 1.9–8.3) and BNT/ChAd (29.1%; 95% CI: 20.1– 39.8) vs BNT/BNT (10.0%; 95% CI: 4.1–19.5) (Figure 2, Supplementary material 7)
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