Sex Differences and Cytokine Profiles among Patients Hospitalized for COVID-19 and during Their Recovery: The Predominance of Adhesion Molecules in Females and Oxidative Stress in Males
Olivera Mitrović-Ajtić,
Dragoslava Đikić,
Tijana Subotički,
Sandra Bižić-Radulović,
Bojana Beleslin-Čokić,
Teodora Dragojević,
Emilija Živković,
Sanja Miljatović,
Milica Vukotić,
Dejana Stanisavljević,
Juan Santibanez,
Vladan P. Čokić
Affiliations
Olivera Mitrović-Ajtić
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
Dragoslava Đikić
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
Tijana Subotički
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
Sandra Bižić-Radulović
Clinic of Hematology, University Clinical Center of Serbia, Dr. Koste Todorovica 2, 11000 Belgrade, Serbia
Bojana Beleslin-Čokić
Clinic of Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Dr. Subotica starijeg 13, 11000 Belgrade, Serbia
Teodora Dragojević
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
Emilija Živković
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
Sanja Miljatović
Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar oslobođenja 16, 11000 Belgrade, Serbia
Milica Vukotić
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
Dejana Stanisavljević
Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Juan Santibanez
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
Vladan P. Čokić
Institute for Medical Research, University of Belgrade, National Institute of Republic of Serbia, Dr. Subotica starijeg 4, 11129 Belgrade, Serbia
The severity and mortality of coronavirus disease 2019 (COVID-19) are greater in males than in females, though the infection rate is the same in the two sexes. We investigated sex hormone differences associated with the hyperinflammatory immune response to SARS-CoV-2 on the basis of patients’ cytokine profiles and vaccination statuses. Clinical and laboratory data of 117 patients with COVID-19 were collected to examine sex differences associated with oxidative stress markers, neutrophil extracellular traps (NETs), and plasma cytokine levels up to 5 months from hospital admission. The testosterone and free testosterone levels were low in male patients with COVID-19 and returned to normal values after recovery from the disease. The dihydrotestosterone (DHT) levels were transiently reduced, while the sex hormone-binding globulin levels were decreased in post-COVID-19 male patients. The levels of the inflammatory cytokines interleukin-6 (IL-6) and IL-10 appeared generally increased at diagnosis and decreased in post-COVID-19 patients. In females, the concentration of tumor necrosis factor-alpha was increased by four times at diagnosis. The levels of the coagulation markers intercellular adhesion molecule-1 (ICAM-1) and E-selectin were consistently upregulated in post-COVID-19 female patients, in contrast to those of vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and chemokine IL-8. DHT increased the levels of reactive oxygen species in the neutrophils of male patients, while estradiol decreased them in females. Markers for NET, such as circulating DNA and myeloperoxidase, were significantly more abundant in the patients’ plasma. Sex hormones have a potential protective role during SARS-CoV-2 infection, which is weakened by impaired testosterone synthesis in men.
