The unique interplay of mitochondrial oxidative phosphorylation (OXPHOS) and immunity and its potential implication for the sex‐ and age‐related morbidity of severe COVID‐19 patients
Yinchuan Li,
Lei Li,
Guanghao Wu,
Gangcai Xie,
Lirong Yi,
Jie Zhu,
ShiYu Liang,
Ya‐ru Huang,
Juan Chen,
Shaoyang Ji,
Fei Sun,
Rui‐tian Liu
Affiliations
Yinchuan Li
Institute of Reproductive Medicine Medical School of Nantong University Nantong Jiangsu P. R. China
Lei Li
National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing P. R. China
Guanghao Wu
School of Materials Science and Engineering Beijing Institute of Technology Beijing P. R. China
Gangcai Xie
Institute of Reproductive Medicine Medical School of Nantong University Nantong Jiangsu P. R. China
Lirong Yi
Institute of Reproductive Medicine Medical School of Nantong University Nantong Jiangsu P. R. China
Jie Zhu
National Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing P. R. China
ShiYu Liang
National Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing P. R. China
Ya‐ru Huang
National Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing P. R. China
Juan Chen
National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing P. R. China
Shaoyang Ji
National Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing P. R. China
Fei Sun
Institute of Reproductive Medicine Medical School of Nantong University Nantong Jiangsu P. R. China
Rui‐tian Liu
National Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing P. R. China
Abstract Aged male patients are more vulnerable to severe or critical symptoms of COVID‐19, but the underlying mechanism remains elusive. In this study, we analyzed previously published scRNA‐seq data from a large cohort of COVID‐19 patients, castrated and regenerated mice, and bulk RNA‐seq of a RNAi library of 400 genes, and revealed that both immunity and OXPHOS displayed cell‐type‐, sex‐, and age‐related variation in the severe or critical COVID‐19 patients during disease progression, with a more prominent increase in immunity and decrease in OXPHOS in myeloid cells in the males relative to the females (60–69 years old). Male severe or critical patients above 70 years old were an exception in that the compromised negative correlation between OXPHOS and immunity in these patients was associated with its disordered transcriptional regulation. Finally, the expression levels of OXPHOS and androgens were revealed to be positively correlated, and the responses of macrophages to android fluctuation were more striking than other types of detected immune cells in the castrated mice model. Therefore, the interplay of OXPHOS and immunity displayed a cell‐type‐specific, age‐related, and sex‐biased pattern, and the underlying potential regulatory role of the hormonal milieu should not be neglected.
