Sex-Specific TMPRSS2 Response and Reduced Peripheral RNA Concentration Following AstraZeneca COVID-19 Vaccination in Nigeria
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Background
ChAdOx1 nCoV-19 remains a cornerstone COVID-19 vaccine in sub-Saharan Africa, yet population-specific molecular responses are understudied. We examined peripheral blood ACE2 and TMPRSS2 expression, total RNA concentration, and coagulation indices in Nigerians ≥6 months post-vaccination.
Methods
In a case-control study in Port Harcourt, Nigeria, 51 ChAdOx1-vaccinated adults and 51 age/sex-matched unvaccinated controls provided venous blood for RNA extraction, qRT-PCR, and coagulation assays. Multivariable linear models assessed effects of vaccination, sex, and age on molecular parameters.
Results
Vaccinated participants had 37% lower total RNA concentration than controls (4.02 ± 0.09 vs 6.38 ± 0.14 ng/μL, p<0.0001). ACE2 and TMPRSS2 expression did not differ by vaccination status overall. However, TMPRSS2 showed a significant sex-by-treatment interaction (p=0.011): vaccinated females had higher expression than vaccinated males. GAPDH expression varied by vaccination status and showed a three-way interaction with sex and age (p=0.027). Coagulation indices were unchanged.
Conclusions
At ≥6 months post-ChAdOx1, Nigerians show reduced peripheral blood RNA without sustained ACE2/TMPRSS2 upregulation. The sex-specific TMPRSS2 pattern suggests hormone×vaccine interactions previously unreported in African cohorts and highlights the need for sex-disaggregated molecular surveillance. Region-specific reference gene validation is recommended for Nigerian transcriptomic studies.
