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
DOI:
https://doi.org/10.7196/SAMJ.2025.v115i8.3121Keywords:
Covid-19 vaccine, thrombosis , d-dimer , HIV, coagulopathyAbstract
Background. Rapid COVID‐19 vaccine development occurred during the pandemic and vaccine‐related complications such as thrombosis with thrombocytopenia syndrome were discovered. Clinical trials and treating facilities included D‐dimer testing in COVID‐19 vaccine trials and COVID‐19 disease‐severity assessments, respectively. D‐dimer testing and result interpretation is complex and its use in isolation is controversial.
Objectives. To evaluate D‐dimer levels in healthy adult participants regardless of HIV status, prior to and 2 weeks after receipt of fractional and full‐dose Ad26.COV2.S or Comirnaty booster COVID‐19 vaccination, after a full dose Ad26.COV2.S prime, stratified by booster vaccination arm, age and HIV status.
Methods. BaSiS, a prospective open‐label trial, enrolled 289 healthy adults. Participants with controlled comorbidities, HIV infection with no immunological or virological exclusions, and no prior thrombosis enrolled at four sites in South Africa (SA). Participants previously received a single Ad26.COV2.S prime vaccination through the Sisonke phase IIIB open‐label implementation study or the COVID‐19 vaccine programme in SA. Participants were randomised 1:1:1:1 to receive one of four boosters: full‐dose Ad26.COV2.S, half‐dose Ad26.COV2.S, full‐dose Comirnaty or half‐dose Comirnaty. D‐dimer testing (INNOVANCE D‐dimer assay), as a coagulopathy marker, was conducted before the booster (baseline) and 2 weeks after the booster. The primary objectives previously reported included safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or Comirnaty in Ad26.COV2.S‐vaccinated participants. An exploratory objective evaluating clotting profiles, measured by D‐dimers, is reported here.
Results. The median age among 285 evaluable participants included in this analysis was 42.2 (interquartile range (IQR): 35.5 ‐ 48.7) years; 82.5% (235/285) were female and 94.4% (269/285) were black African. Of the 40.4% (115/285) of people living with HIV, 79.1% (91/115) were well controlled on antiretroviral therapy. At baseline, 39.3% (112/285) of participants had elevated D‐dimer levels ‒ all asymptomatic. Females and obese participants were significantly more likely to have elevated baseline D‐dimer levels (adjusted odds ratio (aOR): 3.14, 95% confidence interval (CI): 1.32 ‐ 7.48 and aOR: 2.20, 95% CI: 1.22 ‐ 3.96, respectively). Of 276 participants with D‐dimer results available at 2 weeks after the booster, 109 (39.5%) had elevated D‐dimer levels. Those with elevated levels at baseline and female participants (aOR: 14.75, 95% CI: 7.64 ‐ 28.48 and aOR: 3.24, 95% CI: 1.14 ‐ 9.22, respectively) were significantly more likely to have elevated D‐dimer levels at 2 weeks.
Conclusion. Elevated D‐dimer levels in asymptomatic, low‐risk adults were unexpectedly common and not associated with thromboembolism. This supports the rationale of including D‐dimer testing in conjunction with other coagulopathy markers, only if clinically indicated in both COVID‐19 vaccine clinical trials and the general population.
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