Research Highlights: Immune Responses Between Male and Female in COVID-19

An electronic microscope image shows the SARS-CoV-2. (Photo/National Institutes of Health)

Date Published: Aug 26, 2020

Authors: Takehiro Takahashi, Mallory K. Ellingson, Patrick Wong, Benjamin Israelow, Carolina Lucas, Jon Klein, Julio Silva, Tianyang Mao, Ji Eun Oh, Maria Tokuyama, Peiwen Lu, Arvind Venkataraman, Annsea Park, Feimei Liu, Amit Meir, Jonathan Sun, Eric Y. Wang, Arnau Casanovas-Massana, Anne L. Wyllie, Chantal B.F. Vogels, Rebecca Earnest, Sarah Lapidus, Isabel M. Ott, Adam J. Moore, Yale IMPACT research team, Albert Shaw, John B. Fournier, Camila D. Odio, Shelli Farhadian, Charles Dela Cruz, Nathan D. Grubaugh, Wade L. Schulz, Aaron M. Ring, Albert I. Ko, Saad B. Omer & Akiko Iwasaki

  • Clinical outcomes of COVID-19 suggest growing evidence of sex differences.
  • However, whether immune responses against COVID-19 virus differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown.
  • This study examined sex differences in viral loads, COVID-19 virus-specific antibody titers, plasma cytokines, and blood cell phenotyping in COVID-19 patients.
  • By focusing analysis on patients with moderate disease who had not received immunomodulatory medications, the results revealed that male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes.
  • Immunomodulatory drugs modify the response of the immune system by increasing or decreasing the production of serum antibodies.
  • In contrast, female patients produced significantly more robust T cell activation than male patients during COVID-19 viral infection which was sustained in old age.
  • T cells are white blood cells that are important for adaptive immunity.
  • The study found that a poor T cell response negatively correlated with patients’ age and was associated with worse disease outcome in male patients, but not in female patients.
  • Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients.
  • The findings reveal a possible explanation underlying observed sex biases in COVID-19.
  • The study provides an important basis for the development of a sex-based approach to the treatment and care of men and women with COVID-19.


Keywords: immune system, immune response, covid-19 immunity, sex differences in covid-19, males susceptible to covid-19

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