How biological sex affects symptoms and outcomes of COVID-19

Organic sex can be an important factor in how the body responds to a COVID-19 infection. Reports show that certain hormonal differences, genetic factors and sex-linked behaviors are linked to the severity and outcomes of the infection.

It is worth noting that most of the research on this topic focuses primarily on sex at birth and does not take into account intersex people or those who have undergone hormone replacement therapy.

General mortality

Much of the research on how different sexes respond to COVID-19 has focused on outcome and overall mortality. Evidence suggests slightly higher mortality for men than for women. However, researchers point out that men already had higher death rates before COVID-19, due to their higher rates of comorbidities such as cardiovascular disease.

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Skewed due to social factors

Additional studies suggest that a person’s gender has less of an impact on COVID-19 compared to: sex related behaviors. For example, US observational studies reported that male shopkeepers were 1.5 times less likely to wear a mask than women. In addition, men usually make up the majority of workers in fields with higher COVID-19 risks, such as agriculture, construction and maintenance.

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Adaptive immune response

A study from Wuhan showed that women with COVID-19 had higher concentrations of SARS-CoV-2 immunoglobulin G, indicating that they had a much stronger adaptive immune response. This research is consistent with previous studies that have shown that women generally have higher antibody production and stronger vaccine responses, making it easier for them to fight infections such as COVID-19.

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Ratio of Neutrophils to Lymphocytes

Neutrophils and lymphocytes are immune cells that play an important role in protecting against infection. When examining the effects of COVID-19 on the body, researchers noted that higher neutrophil and lower lymphocyte counts were associated with worse outcomes.

Women under 50 and men over 50 had higher neutrophil to lymphocyte ratios than other populations. Researchers believe that routine blood tests measuring this ratio can predict infection severity, but more evidence is needed to discover the ratio’s prognostic value.

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ACE2 and Estrogen

Angiotensin-converting enzyme 2 (ACE2) is an enzyme and receptor that is found on cell surfaces and is most prominent in the heart, kidneys, lungs and plasma. Increasing proof shows that ACE2 plays a role in the entry and invasion of cells by SARS-Cov-2, as well as in the course of infection.

The ACE2 gene is located on the X chromosome. In most other cases, having two copies of a gene – as women do – reduces the effects of X-linked disease, while an increase is noted in men, who have only one. In addition, estrogen can influence ACE2 expression, reduce inflammation and tissue fibrosis, and improve tissue repair.

Concept photo of female sex hormone Estrogen and its level in the body

TMPRSS2 and androgens

Experts also believe that there may be sex-related differences in the interaction of COVID-19 with transmembrane serine protease 2 (TMPRSS2), a gene most known for its association with prostate cancer.

The virus uses TMPRSS2 to invade and attach to cells. Androgens, which are responsible for male characteristics, are the only known stimuli for TMPRSS2 gene transcription. In patients with prostate cancer, androgen deprivation therapy reduced the risk of COVID-19 infection.

In addition, people with androgenic alopecia are much more likely to have severe COVID symptoms. This evidence could indicate that men are more at risk for infection than women and could explain why young children tend to have less severe symptoms.

Papers with hormones list and tablet with words androgens.

Deliver function

Through various mechanisms, such as cellular toxicity and inflammation, COVID-19 can damage the liver. Experts found higher levels of certain biomarkers in patients with COVID, with links to worse symptoms and mortality. Among these patients, men had considerable higher amounts of those biomarkers.

Some researchers believe this evidence suggests that men are at greater risk for liver-related problems as a result of COVID-19 infection.

The photo of the liver on a man's body against a gray background Tharakorn / Getty Images

Coagulation Problems

People with severe COVID-19 often develop impaired blood clotting. In a studyMore than 70% of patients who died from COVID-19 had a relatively rare blood clotting disorder, compared to 0.6% of survivors.

Studies on clotting factors suggest that women generally have much more favorable outcomes, especially if they are premenopausal. Men are more likely to have atypical blood clotting and other symptoms.

In the hospital the sick male patient is sleeping on the bed gorodenkoff / Getty Images

Hormone Replacement Therapy

Sex steroids such as testosterone, estrogen and progesterone are notable regulators of immune and inflammatory responses. Pre-menopausal estrogen has potent anti-inflammatory properties. Testosterone may have a similar effect, in addition to anabolic abilities that reduce the risk of lung damage.

People with lower levels of sex steroids, such as older adults, may benefit from: hormone replacement therapy to treat long-term COVID symptoms.

Hormone Replacement Therapy BSIP/UIG / Getty Images

Future treatments

Sex differences can also alter the effectiveness of COVID-19 treatments. The upregulation of type 1 interferon (IFN) by toll-like receptors is an integral defense mechanism against viruses. These receptors are 10 times more common in women than in men. In addition, testosterone has a negative effect on IFN.

Currently, IFN therapy is: being investigated as a COVID treatment. Women can respond much more vigorously to the therapy than men. This carries many potential risks, so future treatments can be highly targeted and even gender-dependent.

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