Males and Females have Different Immune Responses to COVID-19

NIAID Now | August 26, 2020

Increasing evidence shows that men tend to have more severe symptoms of COVID-19 and a higher death rate than women with the disease. To investigate whether there are sex-based differences in the body’s immune responses to infection with SARS-CoV-2, the virus that causes COVID-19, a NIAID-funded clinical research study enrolled males and females who were admitted to the hospital with moderate or severe COVID-19.

Blood, nasal swabs, and saliva, urine, and stool samples were collected at the time of enrollment and every 3 to 7 days after that. Investigators compared immune responses between participants who recovered and those who progressed to more severe stages of disease. Males and females were matched by age, body mass index, and the number of days after their symptoms began. Additionally, a group of healthcare workers not infected with SARS-CoV-2 was used as a control group.

Several key differences in immune responses were seen between males and females with COVID-19. Males had higher blood levels of several proteins called cytokines, which regulate the immune response, including two inflammatory cytokines known as IL-8 and IL-18, at the time of study enrollment (baseline) and over the disease course. Males also had lower baseline activation of immune cells called CD8 T cells, which can recognize and help eliminate invading viruses. 

As COVID-19 progressed in study participants, males, but not females, showed associated poor T-cell responses. Likewise, T-cell responses declined with age in males but not females. By contrast, researchers identified elevated levels of a different set of cytokines in females, but not males, that were associated with worsening of disease.

These findings reveal a possible immunological basis for the differences in disease outcomes between males and females with COVID-19 and provide a potential basis for taking sex-dependent approaches in the treatment of COVID-19.

Reference: Takahashi T et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020 Aug 26; 588(7837): 315-320.

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