MAIT Cell Response May Explain Women’s Lower Severe COVID-19 Rate


Women suffer severe COVID-19 at around half the rate as men, but the reason for this has been unclear. Now, research1 has found that women have different levels of mucosal-associated invariant T cells, and these immune cells amass in the lungs, poised to attack the COVID virus.

Better armed with these specialized immune cells, women appear to be more equipped to fight some of the most severe impacts of COVID-19, notably the respiratory infections that can become life-threatening,

says Dr. Daniel Saban, an associate professor in the ophthalmology department and in the immunology department at Duke University.

Unbiased Approach

Saban says the investigation began last spring as COVID first spread and he was sidelined from his normal caseload studying eye diseases. A piece of equipment in his lab — a device that can perform 36-color flow cytometry — was sitting idle, so he decided to use it to examine blood samples from COVID patients.

We didn’t start with a hypothesis. It was a completely unbiased approach, where we asked our colleagues to provide blood and tissue samples from COVID patients as well as healthy people. We had no idea what we would find, if anything,

Saban says.

The researchers quickly saw that the white blood cell called mucosal-associated invariant T cells, (MAIT cells), circulated more abundantly in the blood of healthy women compared to healthy men. MAIT cells are highly specialized white blood cells that contribute to immune defences in mucosal organs and tissues2.

Robust MAIT Cells

Among COVID patients, however, there were few MAIT cells circulating in the blood, even among women, where the population of MAIT cells radically fell off, leading the researchers to question where these cells had gone.

They found their answer in tissue samples from the lungs of COVID patients. Overall, there was an abundance of MAIT cells in the lung tissue of people with COVID, but upon closer inspection, they found night-and-day differences between the sexes.

We first found this dichotomy in healthy blood. Circulating MAIT cells in women expressed genes indicative of a robust profile poised for fighting an infection, but this was not the case in males. Then we looked in the tissue and were able to find evidence of this same pattern by sex,

Saban explains.

Saban says there are numerous examples of sexual differences in the immune responses to infections, noting those differences have been prevalent all along with COVID-19.

Our findings uncover a female-specific protective profile carried out by these MAIT cells, and this could potentially help guide the development of treatments and therapies,

he adds.

  1. Yu, C., Littleton, S., Giroux, N.S., Mathew, R., Ding, S., Kalnitsky, J., Yang, Y., Petzold, E., Chung, H.A., Rivera, G.O., Rotstein, T., Xi, R., Ko, E.R., Tsalik, E.L., Sempowski, G.D., Denny, T.N., Burke, T.W., McClain, M.T., Woods, C.W., Shen, X., Saban, D.R., Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19, Med (2021) PII: S2666-6340(21)00157-4 ↩︎
  2. Nel, I., Bertrand, L., Toubal, A. et al. MAIT cells, guardians of skin and mucosa?. Mucosal Immunol (2021) ↩︎

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Last Updated on September 12, 2023