Mother-Daughter Researchers Share Why COVID-19 Affects Men More than Women

Why are men more vulnerable to coronavirus? A recent study, that is up for peer review has proposed that presence of testicles in men makes them more vulnerable to longer and more severe cases COVID-19. The team behind this research is the mother-daughter duo of Dr Jayanthi Shastri and Dr Aditi Shastri.  While Dr Jayanthi is heading the microbiology department in a leading Mumbai hospital, her daughter is an AssistantProfessor of Oncology at Montefiore Medical Center & Albert Einstein College of Medicine, in Bronx, New York. The two collaborated on the research across continents.

The duo speaks with SheThePeople.TV about their research, other factors which could be responsible for high fatality rate among men from COVID-19, and how they collaborated on the research despite living in two separate corners of the world.

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Your study, which is yet to be published, says testicles could be key to the vulnerability of men for SARS-CoV2, what drew your attention to that?

Aditi and Jayanthi: We worked in our own individual capacities to arrive at this joint conclusion. When Dr.Jayanthi Shastri analysed the Kasturba Hospital patient data, she found that men are taking on an average two days longer to clear the novel coronavirus infection compared to women. The team also found three families where the female members cleared the infection sooner than the males. My team found that the ACE2 receptor which is the entry point for the novel coronavirus into the human body was found in abundance in the testes (male gonadal tissue) however it was entirely absent in the ovaries. This finding led us to hypothesize that the testes or male gonadal tissue could be a reservoir for the novel coronavirus and could be the reason that males take longer to clear the infection.

It is becoming apparent from several reports across the world that men are suffering from increased morbidity and mortality from COVID-19 compared to women. Delayed clearance could be contributing to men having longer symptoms and worse outcomes from the disease.

Could you explain what delayed clearance means and how it plays a crucial role in making men more susceptible to SARS-CoV2?

Aditi and Jayanthi: Oropharyngeal/nasopharyngeal swabs are collected from suspected patients with COVID symptoms and then an RT-PCR (Reverse transcription polymerase chain reaction) test is run to see if they are positive or negative for infection. Once confirmed to be positive, this test is repeated every 48 hours approximately until there are 2 negative swabs which helps confirm that the patient has cleared the infection. It is becoming apparent from several reports across the world that men are suffering from increased morbidity and mortality from COVID-19 compared to women. Delayed clearance could be contributing to men having longer symptoms and worse outcomes from the disease.

Dr Jayanthi Shastri in Lab

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How does high levels of ACE2 receptors in testicles fit into this picture?

ACE-2 or Angiotensin receptor-2 is the critical receptor that interacts with the novel coronavirus's spike proteins and facilitates the entry of this virus into human cells. Having the ACE2 receptor expressed in tissues is critical to mediate the entry of the virus into that human tissue. High levels of the ACE2 receptor in the testes signifies that the virus can bind to the male gonadal tissue with increased avidity (more affinity, if loosely translated).

What are the factors that further contribute to the high fatality rate among men for SARS-CoV2?

Aditi and Jayanthi: There have been multiple factors cited in the scientific literature , scientific and lay press for why men have higher fatality rates with the novel coronavirus. Men have higher rates of smoking, more chronic health conditions such as diabetes and heart disease compared to women. Men also use hand hygiene less often than women. Women have been thought to have a more vigilant immune system that can ward off/evade infection compared to men.

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Do testicles endure any damage due to being viral reservoirs? Could there be a specific symptom, that medical examiners can look for among suspected patients of coronavirus?

Aditi and Jayanthi: We are currently not sure if testicles do suffer damage and are currently in the process of doing tests to confirm our hypothesis that the testis is a viral reservoir. There is a preprint from China that describes sexual hormone dysfunction in males with COVID infection compared to their healthy counterparts. However, larger studies need to be done to further confirm this finding. At this time, we do not recommend that medical examiners check sex hormones among suspected patients with COVID infection until we have further evidence of testicular damage and understand the long term implications of the effect of the novel coronavirus on male sexual function.

Women have been thought to have a more vigilant immune system that can ward off/evade infection compared to men.

How could your study have implications on the understanding of the persistence of SARS-CoV2 infection in humans?

Aditi and Jayanthi: Our study was the first pre-print (to our knowledge) to demonstrate that men take longer to clear the coronavirus infection compared to women and that the testes could be a viral reservoir given the very high ACE2 receptor expression. We have provided a biological hypothesis for the persistence of the novel coronavirus infection in males. This hypothesis may have important implications for understanding the transmission and persistence of the virus in humans in a gender-specific manner.

Dr Aditi Shastri in Lab

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Are there any gender-specific measures that can be taken to contain transmission?

Aditi and Jayanthi: At this time, we do not recommend any gender-specific measures to contain transmission until we have further evidence of testicular damage and understand the long term implications of the effect of the novel coronavirus on male sexual function.

Being situated in two different corners of the world, how did you work on the findings together?

(Dr Aditi) My mother and I are very close and we speak almost every day. We are both in the car when we speak. I'm driving to work here early in the morning in New York and she is getting home after a long day of work in Mumbai. This research idea materialized out of our daily conversations.

Have you submitted your study for peer review? What will be your focus be on, once this is published?

Aditi and Jayanthi: Yes, we have submitted the manuscript for peer-review. Our focus will be on trying to confirm our hypothesis of a male gonadal reservoir for the novel coronavirus.

Image Credit: Dr Aditi Shastri