TY  -  JOUR
AU  -  Knapp, Johannes D
AU  -  Bhargava, Aditi
T1  -  BNT162b2 mRNA vaccine booster dose-induced sex differences in the single-cell transcriptome of peripheral blood mononuclear cells in healthy adults: preliminary evidence
PY  -  2024
Y1  -  2024-05-01
DO  -  10.1723/4297.42782
JO  -  Journal of Sex- and Gender-Specific Medicine
JA  -  J Sex Gender Specif Med
VL  -  10
IS  -  2
SP  -  56
EP  -  68
PB  -  Il Pensiero Scientifico Editore
SN  -  2974-8623
Y2  -  2026/04/23
UR  -  http://dx.doi.org/10.1723/4297.42782
N2  -  Summary. Introduction. Men reportedly experience more severe disease and adverse outcomes from COVID-19, including death. Women report more adverse events (AEs) after vaccination in general. While few studies have addressed sex-specific risk factors or molecular mechanisms behind COVID-19, none have examined sex differences in the response to COVID-19 vaccination. Methods. We searched AE reporting databases to find sex differences specific to COVID-19 vaccines. Public datasets were analyzed to identify baseline and BNT162b2 mRNA vaccine booster dose-induced sex differences in single cell transcriptome across various immune cell types and time points in healthy adults with no prior SARS-CoV-2 infection. Results. Sex differences in AE rates for mRNA vaccines equaled those for other non-mRNA vaccines. T cells and monocytes showed the greatest number of sex differences in transcriptome. Platelet counts in the study population differed significantly before vaccination (3.6% in females vs 1.8% in males); a booster BNT162b2 dose induced more platelets in men, thereby abrogating sex differences (7.2% vs 7.3%). Platelets accounted for most observed sex differences in single cell transcriptome after mRNA vaccination. BNT162b2 booster dose2-specific APOBEC3Ahigh monocytes and the booster dose-induced transcript signature in de novo cluster 8 cells persisted for longer in women. BARD1 in hematopoietic stem cells was the only transcript that increased in males but decreased in females following the booster dose. Glucocorticoid-responsive genes TSC22D3, CEBPB/D and DDIT4 were specifically induced in females. Conclusions. This sexual dimorphism in both X-linked and autosomal gene transcriptome in PBMCs offers a window into mechanisms that might explain different rates of fatigue, autoimmune, and neurological AEs reported in women and men after COVID-19 mRNA booster dose.
ER  -