TY - JOUR
T1 - Delineating sex-specific circulating host response signatures associated with COVID-19 severity and mortality
AU - Keur, Nick
AU - Flikweert, Antine W
AU - Ricaño-Ponce, Isis
AU - Muller Kobold, Anneke C
AU - van der Sar-van der Brugge, Simone
AU - Rodenhuis-Zybert, Izabela A
AU - Le, Kieu T T
AU - van Meurs, Matijs
AU - Grootenboers, Marco J
AU - van der Voort, Peter H J
AU - Heeringa, Peter
AU - Kumar, Vinod
AU - Moser, Jill
N1 - © 2024 The Author(s).
PY - 2024/11/15
Y1 - 2024/11/15
N2 - Male SARS-CoV-2-infected patients have higher hospitalization rates, ICU admissions, and mortality compared to females, yet with unclear underlying mechanisms. We investigated the influence of biological sex on COVID-19 severity and patient outcomes. We profiled 41 circulating host response markers and identified differentially regulated proteins based on disease severity using covariates, such as sex, age, BMI, diabetes, and corticosteroid administration. IL-8, D-dimer, S100B, IL-6, Angpt-2, MMP-8, TNF-R1, u-PAR, u-PA, osteopontin, IL-13, TNF-α, pentraxin-3, P-selectin, fractalkine, and SP-D levels were elevated in critically ill COVID-19 males compared to severe cases. In contrast, IL-8, D-dimer, IL-6, Angpt-2, Tie-2, uPAR, and SP-D were higher in females with critical-COVID-19 than in severe cases. Notably, D-dimer, IL-6, pentraxin-3, and S100B were associated with male mortality, yet none of the measured plasma proteins associated with female mortality. Our study delineated distinct sex-specific plasma protein signatures linked to the severity and mortality of COVID-19 patients.
AB - Male SARS-CoV-2-infected patients have higher hospitalization rates, ICU admissions, and mortality compared to females, yet with unclear underlying mechanisms. We investigated the influence of biological sex on COVID-19 severity and patient outcomes. We profiled 41 circulating host response markers and identified differentially regulated proteins based on disease severity using covariates, such as sex, age, BMI, diabetes, and corticosteroid administration. IL-8, D-dimer, S100B, IL-6, Angpt-2, MMP-8, TNF-R1, u-PAR, u-PA, osteopontin, IL-13, TNF-α, pentraxin-3, P-selectin, fractalkine, and SP-D levels were elevated in critically ill COVID-19 males compared to severe cases. In contrast, IL-8, D-dimer, IL-6, Angpt-2, Tie-2, uPAR, and SP-D were higher in females with critical-COVID-19 than in severe cases. Notably, D-dimer, IL-6, pentraxin-3, and S100B were associated with male mortality, yet none of the measured plasma proteins associated with female mortality. Our study delineated distinct sex-specific plasma protein signatures linked to the severity and mortality of COVID-19 patients.
U2 - 10.1016/j.isci.2024.111150
DO - 10.1016/j.isci.2024.111150
M3 - Article
C2 - 39507250
SN - 2589-0042
VL - 27
JO - Iscience
JF - Iscience
IS - 11
M1 - 111150
ER -