| Autor: |
Hamlin, Rebecca E., Pienkos, Shaun M., Chan, Leslie, Stabile, Mikayla A., Pinedo, Kassandra, Rao, Mallika, Grant, Philip, Bonilla, Hector, Holubar, Marisa, Singh, Upinder, Jacobson, Karen B., Jagannathan, Prasanna, Maldonado, Yvonne, Holmes, Susan P., Subramanian, Aruna, Blish, Catherine A. |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 11/13/2024, Vol. 16 Issue 773, p1-20, 20p |
| Abstrakt: |
Sex differences have been observed in acute coronavirus disease 2019 (COVID-19) and Long Covid (LC) outcomes, with greater disease severity and mortality during acute infection in males and greater proportions of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to LC pathogenesis. To investigate the immunologic underpinnings of LC development and symptom persistence, we performed multiomic analyses on blood samples obtained during acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 3 and 12 months after infection in a cohort of 45 participants who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Males who would later develop LC exhibited increases in transforming growth factor–β (TGF-β) signaling during acute infection, whereas females who would go on to develop LC had reduced TGFB1 expression. Females who developed LC demonstrated increased expression of XIST, an RNA gene implicated in autoimmunity, during acute infection compared with females who recovered. Many immune features of LC were also conserved across sexes, such as alterations in monocyte phenotype and activation state. Nuclear factor κB (NF-κB) transcription factors were up-regulated in many cell types at acute and convalescent time points. Those with ongoing LC demonstrated reduced ETS1 expression across lymphocyte subsets and elevated intracellular IL-4 in T cell subsets, suggesting that ETS1 alterations may drive aberrantly elevated T helper cell 2–like responses in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics. Editor's summary: Sex differences have been reported for both acute coronavirus disease 2019 (COVID-19) and Long Covid (LC), with males typically having more severe acute disease and females being more likely to develop LC. Here, Hamlin et al. performed multiomics on peripheral blood samples from a prospective cohort of individuals to understand why. The authors identified immune pathways during acute infection that were associated with later development of LC. Some pathways, such as alterations in monocyte activation, were shared between the sexes; others were unique to males or females. This study both highlights the heterogeneity of LC and suggests that immunomodulatory treatments need to be tailored to the individual. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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