Sex differences in inflammation, mitochondrial function and energy sensing during early recovery from COVID 19 in older adults
Abstract
SARS-CoV-2 infections induce mitochondrial dysfunction and exacerbate systemic inflammation. In the present study, sex differences were investigated among post-COVID-19 patients during the early recovery phase, as emerging evidence indicates that sex critically influences post-COVID-19 outcomes, particularly in older adults. Mitochondrial dysfunction, energy stress signaling through AMP-activated protein kinase (AMPK), and inflammatory dysregulation represent pathogenic mechanisms implicated in prolonged recovery. In this study, we analyzed peripheral blood mononuclear cells (PBMCs) and plasma from aged male and female patients during early post-COVID-19 recovery (1–4 weeks after obtaining a negative SARS-CoV-2 PCR test), comparing them to an inflammatory control group. Female post-COVID-19 patients exhibited elevated circulating TNF-α levels and a trend toward increased mRNA levels of proinflammatory interleukins IL-1β and IL-18 in PBMCs, accompanied by enhanced acetylation and decreased activity of mitochondrial superoxide dismutase 2 (SOD2). Both sexes displayed increased phosphorylation of AMPK, suggesting altered energy-sensing pathways. Mitochondrial gene expression was upregulated in female post-COVID-19 patients, potentially indicating compensatory responses to energy deficits. These findings reveal sex-dependent inflammatory and mitochondrial alterations during early recovery, suggesting a mechanistic link to the higher prevalence of long COVID-19 in women. These findings emphasize the need for sex-specific therapeutic approaches targeting mitochondrial and immunometabolic dysfunction in post-COVID-19 patients.
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BibTeX
@article{temp2026differences,
title = {{Sex differences in inflammation, mitochondrial function and energy sensing during early recovery from COVID 19 in older adults}},
author = {Julia Temp and Misael Estepa and Michael Nnaji and Natalie Haritonow and Louis Marx and Olesya Vakhrusheva and Haiyan Wu and Yury Ladilov and Maria Luisa Barcena},
journal = {Scientific Reports},
year = {2026},
month = nov,
doi = {10.1038/s41598-026-75978-z},
url = {https://www.nature.com/articles/s41598-026-75978-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sex differences in inflammation, mitochondrial function and energy sensing during early recovery from COVID 19 in older adults
AU - Julia Temp
AU - Misael Estepa
AU - Michael Nnaji
AU - Natalie Haritonow
AU - Louis Marx
AU - Olesya Vakhrusheva
AU - Haiyan Wu
AU - Yury Ladilov
AU - Maria Luisa Barcena
PY - 2026
DA - 2026/11/04
JO - Scientific Reports
DO - 10.1038/s41598-026-75978-z
UR - https://www.nature.com/articles/s41598-026-75978-z
AB - SARS-CoV-2 infections induce mitochondrial dysfunction and exacerbate systemic inflammation. In the present study, sex differences were investigated among post-COVID-19 patients during the early recovery phase, as emerging evidence indicates that sex critically influences post-COVID-19 outcomes, particularly in older adults. Mitochondrial dysfunction, energy stress signaling through AMP-activated protein kinase (AMPK), and inflammatory dysregulation represent pathogenic mechanisms implicated in prolonged recovery. In this study, we analyzed peripheral blood mononuclear cells (PBMCs) and plasma from aged male and female patients during early post-COVID-19 recovery (1–4 weeks after obtaining a negative SARS-CoV-2 PCR test), comparing them to an inflammatory control group. Female post-COVID-19 patients exhibited elevated circulating TNF-α levels and a trend toward increased mRNA levels of proinflammatory interleukins IL-1β and IL-18 in PBMCs, accompanied by enhanced acetylation and decreased activity of mitochondrial superoxide dismutase 2 (SOD2). Both sexes displayed increased phosphorylation of AMPK, suggesting altered energy-sensing pathways. Mitochondrial gene expression was upregulated in female post-COVID-19 patients, potentially indicating compensatory responses to energy deficits. These findings reveal sex-dependent inflammatory and mitochondrial alterations during early recovery, suggesting a mechanistic link to the higher prevalence of long COVID-19 in women. These findings emphasize the need for sex-specific therapeutic approaches targeting mitochondrial and immunometabolic dysfunction in post-COVID-19 patients.
SN - 2045-2322
ER -