Sex steroids could explain why Covid-19 is more severe for men than women

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  • Reproductive hormones in female biology may be better equipped at fighting off the inflammation caused by the coronavirus infection
  • Oestrogen, progesterone, and allopregnanolone have anti-inflammatory properties, can increase anti-body production and repair respiratory cells
  • Older women however lose this protective layer post-menopause

In most societies around the world, women tend to outlive men. In the Covid-19 pandemic, that demographic quirk is even more pronounced as men are twice as likely as women to suffer from severe complications from the coronavirus. 

Earlier research into this phenomenon has highlighted differences in antibodies, immune responses that control inflammation and circulating proteins. But discovering why these differences exist has been an ongoing quest for the science community. 

A new study published in Trends in Endocrinology and Metabolism however looks at one of the key differences between men and women’s biology - sex steroids. Women have higher levels of oestrogen, progesterone, and allopregnanolone important in the process of reproduction.

But these steroids aren’t just for making babies - they also manage and control inflammation in the body, which is one of Covid-19’s biggest weapons against the human body.

READ | More evidence shows why Covid mortality rate is higher in men

Progesterone

Progesterone, alongside another steroid oestradiol, also has neural influences, act as anti-inflammatories, can boost immune cells and increase antibody production. This helps pregnancies be more viable without being labelled as intruders in the woman’s body.

And when the body is under stress from a virus, it can trigger self-healing in respiratory cells - exactly where SARS-CoV-2 likes to proliferate - and increase T-cell production to fight off the infection.

“In females, a faster recovery of the lung tissue may reduce the susceptibility to secondary bacterial infection, which is the primary cause of mortality after influenza virus infection,” explain the researchers. 

“This finding is substantiated by studies showing that following influenza A virus infection, the histological density of pulmonary inflammation was decreased during pregnancy.”

Oestrogen and allopregnanolone

Oestrogen acts similarly to progesterone as it helps regulate the immune system and can reduce the production of cytokines. Oestradiol also decreases ACE2 receptors in the lung, the coronavirus’s favourite entry point into cells. 

Allopregnanolone, on the other hand, is produced in the brain and helps regulate our moods and cognition. 

Neurological conditions like postpartum depression, post-traumatic stress disorder, alcohol use disorder, epilepsy, and Alzheimer’s disease can induce inflammation in the body. Pregnenolone and allopregnanolone combat this by inhibiting the inflammation TLR4 signals and is often used to treat specifically postpartum depression.

“Since Covid-19 is characterised by excessive TLR4 signals in the lungs, marked by the overexpression of proinflammatory cytokines, including IL-6 and TNF-α and culminating with the cytokine storm, allopregnanolone may protect against Covid-19-induced inflammation,” adds the researchers.

READ MORE | Your contraceptive pill may be protecting you against the coronavirus, according to a study

Menopause and pregnancy

Women also start losing these protective sex steroids when they enter menopause, making older women also more susceptible to Covid-19 like men. 

This was already studied in earlier research where pre- and post-menopausal women’s resilience against the virus were compared, indicating that low oestrogen made older women a bigger target for the coronavirus.

Pregnancy - when these sex steroids are at an all-time high - also appears to have some increased protection against Covid-19, however their symptoms if infected become exacerbated after giving birth when the levels decrease suddenly. 

In the US, the number of Covid-19 deaths among pregnant women was below 1%, compared to the 2.24% mortality rate of all women in the country. 

Future treatments

“The anti-inflammatory action, the role in reshaping immuno-competence and increasing number of immune cells, and the stimulation of higher antibody concentrations against viral infections raise the hypothesis that these reproductive steroids may be beneficial to prevent or improve Covid-19 symptom severity and mortality,” concludes the study. 

“Clinical trials should test whether these hormones offer benefits in men and in postmenopausal women at risk of developing severe Covid-19 symptoms.”

READ | Like jiggling a key that doesn't fit into a lock - how the coronavirus tricks its way into cells

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