Gender Differences Associated with Hyper-Inflammatory Conditions in COVID-19 Patients

COVID-19 has been associated with various hyper-inflammatory conditions (HICs) such as macrophage activation, hematological dysfunction, cytokinaemia, coagulopathy, and liver inflammation. However, it is not clear if the differences in the disease severity and mortality shown by male and female COVID-19 patients are associated with these HICs. Here, we review the literature and present supporting laboratory data on the gender differences associated with various HICs in COVID-19 patients. We measured plasma/serum levels of various HIC specific clinical markers in severe male (N=132) and severe female (N=78) COVID-19 patients. The result revealed that all clinical markers were highly elevated above the normal in both male and female COVID-19 patients. However, a comparison of AUROC (area under the receiving operative characteristics) of specific clinical markers revealed that elevation in serum ferritin (marker for macrophage activation), and neutrophil to lymphocyte (N/L) ration (marker for hematological dysfunction) was much higher in male compared to the female COVD-19 patients. Further, univariate regression analyses revealed that male COVID-19 patients had two times higher risks than female patients for developing macrophage activation (OR 2.36, P=0.004)), hematological dysfunctions (OR 2.23, P=0.01), coagulopathy (OR 2.10, P=0.01), and cytokinaemia (OR 2.31, P=0.01). Similar results were obtained in bivariate analyses. Survival curve analysis showed that male COVID-19 patients had relatively short survival duration than female COVID-19 patients (hazard ratio 2.0, 95% CI 1.3-3.7, P=0.01). The above findings suggest that the high mortality rate in male COVID-19 patients compared to the female could be due to higher prevalence and severity of various HICs.