Clot Twist - D-dimer analysis of healthy adults receiving heterologous or homologous booster COVID-19 vaccine after a single prime dose of Ad26.COV2.S in a phase II randomised open-label trial, BaSiS. (preprint)

ABSTRACT

BaSiS (Booster After Sisonke Study) is a prospectively enrolled open-label trial in which healthy adults, with controlled co-morbidities and no prior thrombosis, who received a single Ad26.COV2.S prime vaccination primarily through the Sisonke phase IIIB open label implementation study in South Africa. An exploratory objective evaluated the clotting profiles of participants who were enrolled across 4 sites in South Africa and randomised 1111 to receive one of full-dose Ad26.COV2.S, half-dose Ad26.COV2.S, full-dose Comirnaty or half-dose Comirnaty booster. D-dimer testing (INNOVANCE D-Dimer Assay), as a coagulopathy marker, was conducted pre-booster (baseline) and 2 weeks post-booster. The median age among 285 participants was 42.2 years (IQR35.5-48.7), 235/285 (82.5%) were female, 269/285 (94.4%) were Black African. Of the 40.4% (115/285) people living with HIV (PLHIV), 79.1% (91/115) were well-controlled on antiretroviral therapy. At baseline, 39.3% (112/285) had elevated d-dimers; all asymptomatic. Females and obese participants were significantly more likely to have elevated baseline d-dimers (OR=4.17; 95% CI1.88 to 9.26 and OR=2.64; 95% CI1.57 to 4.43, respectively). Of 169 with normal baseline d-dimers, 29 (17.2%) became elevated 2 weeks post-booster median increase 0.23ug/ml (IQR0.15-0.42); those receiving full-dose Comirnaty exhibited lower risk of d-dimer elevation post vaccination, compared to other booster vaccination arms (OR0.26; 95% CI0.07 to 0.98). PLHIV experienced significantly higher median increases compared to HIV uninfected participants (0.43 vs 0.17, p=0.004). Elevated d-dimers in asymptomatic, low-risk adults were unexpectedly common but were not associated with thromboembolism, supporting the rationale of using d-dimers only if clinically indicated. Trial Registration South African Clinical Trails Register number DOH-27-012022-7841.