COVID-19 & Women’s Health: Frequently Asked Questions

1. Are women at a higher risk of contracting COVID-19 than men?

The answer to this question is unfortunately, not as straightforward as yes or no. Current data does not show a significant difference in the number of cases between the sexes, so at a first glance one may be inclined to answer “no.” But there are more factors at play than biology that contribute to the risk of contracting COVID-19. Societal behavioural patterns impact our risk as well, such as gender identity.

Sit tight, because this question requires a far greater in-depth analysis than you would expect. If you are not in the mood for a longer read, feel free to skip to the TL;DR sections of this topic.

To clarify, sex refers to the physical, anatomical difference between individuals that determines whether they are assigned female, male, or intersex. Generally, people are assigned male or female at birth, and this is referred to as the sex binary.

Gender, on the other hand, is a socially constructed concept that pertains to roles and behaviour expected of the sexes. Gender also includes one’s sense of gender identity and expression. Gender is a continuum, meaning that it can change over time. Gender also exists on a spectrum, meaning that gender identity and expression varies by individual and cannot be pinned down as “one or the other.”

An example that illustrates gender differences would be the societal association of pink vs. blue. In today’s society, we automatically assume an infant dressed in pink is female, whilst a baby in blue is assumed male. There is nothing inherently masculine or feminine about either colour other than the stereotypes our society perpetuates regarding blue vs. pink.

So, what does this have to do with a man or woman’s risk of contracting COVID-19?

TL;DR: The answer is that sex alone is not enough to determine risk, as societal gender roles also affect people’s exposure to the virus, ability to access healthcare, and willingness to access healthcare.

Our current research has determined that a certain protein, called ACE2, is needed for the COVID-19 virus to enter and infect the body’s cells. The ACE2 protein is located on a cell’s surface and is needed for normal cell functioning and signalling. The protein is most abundant in the lungs, heart, kidneys, small intestines, and testes. COVID-19 binds to ACE2 using its spike protein (S). In order to bind to ACE2, the S protein must be primed by another host-cell protein: transmembrane protease serine 2 (TMPRSS2). Again, TMPRSS2 is needed for normal physiological processes, and the virus is exploiting this feature to infect and spread.

ACE2 is an important protein that helps regulate blood pressure. A decrease in ACE2 protein expression in the body is associated with cardiovascular disease. Furthermore, issues with circulation are linked to a higher risk of COVID-19. Many patients who are admitted to ICU for COVID-19 have high blood pressure, type 2 diabetes, heart failure, or other circulatory diseases.

The gene for ACE2 is sex-linked, encoded on the X chromosome. Therefore, females have 2 copies of this gene whilst males only have 1. Counterintuitively, the additional copy of the gene that females carry may confer an advantage against COVID-19 rather than simply increasing susceptibility or symptom severity.

ACE2 downregulation by COVID-19 after infection is thought to result in worse health outcomes. To understand why this is the case, we must look to the renin-angiotensin-aldosterone system (RASS), a complex pathway of interacting enzymes and chemicals that regulate blood pressure in the body. The classical pathway involves the production of angiotensin II, a hormone, by angiotensin converting enzyme (ACE). The effects on angiotensin II on the body results in increased blood pressure. This is the classical RAAS pathway.

The ACE2 axis is a recently discovered alternative pathway that results in an opposite effect of the classical pathway. ACE2 converts angiotensin II to a different hormone called Ang 1-7. Ang 1-7 lowers blood pressure, is anti-inflammatory, and anti-fibrotic.

After infecting a cell and decreasing ACE2 gene expression, COVID-19 also increases expression of a different hormone called ADAM-17 (sometimes also referred to as TACE). ADAM-17 is responsible for the activation of multiple different pro-inflammatory chemicals in the body. Plus, increased activity of the classical RAAS pathway increases ADAM-17 activity too. It is believed that ADAM-17 activity is linked to disease severity of COVID-19.

In theory, the 2 ACE2 genes women carry can help compensate for the decrease in cell membrane ACE2 caused by COVID-19. Furthermore, the increased genetic variability of ACE2 through a mosaic advantage of gene expression in females may also decrease susceptibility and disease severity.

The TMPRSS2 protein that is needed to mediate cell entry via ACE2 by the virus is thought to be impacted by sex as well. TMPRSS2 is sensitive to androgens (male hormones). It is thought that this sensitivity may promote viral fusion and entry into the cell. TMPRSS2 may also respond to estrogen, however, so the extent of sex hormones on the expression and activity of TMPRSS2 is not clear.

TL;DR: There are proteins called ACE2, ADAM-17, and TMPRSS2 that are related to understanding the infectivity and severity of COVID-19. The difference between the sexes in gene diversity, expression, and activity of the proteins ACE2, ADAM-17, and TMPRSS2 may explain the increased morbidity and mortality seen in males.

If we step back and look at the differences between male and female immune response, we see that historically men are more susceptible to viral infections in general. We could easily write a book explaining in detail how different components of the immune system differs between the sexes, but we doubt our readers will want to have to read a long winded paper to answer one question.

In a nutshell, women will mount a faster and more aggressive immune response to a pathogen. Women’s white blood cells are better at digesting pathogens and will make more antibodies. Women’s immune systems are also more sensitive than men’s, which helps explain why autoimmune diseases are more prevalent among women. Men, on the other hand, will produce more pro-inflammatory chemicals as part of their immune response. The pro-inflammatory state can cause damage if it is overly extensive or prolonged. This may help explain why more men are admitted to the ICU for COVID-19 than women.

TL:DR: Women’s immune response is faster and stronger than men. Men tend to produce more inflammatory chemicals which damage tissues, which may explain why they tend to have more severe symptoms.

Sex hormones affect immune modulation as well. Estrogen is known to increase antibody production, an promote anti-viral activity in immune cells. On the other hand, male hormones can dampen the immune response. Estrogen is also known to confer cardioprotection in premenopausal women. As cardiovascular disease (CVD) is a risk factor for severe COVID-19, estrogen may offer an advantage against the virus. Estrogen levels drop after menopause. Post-menopausal women who take estrogen in hormone replacement therapy (HRT) within 10 years of menopause has been shown to reduce the risk of CVD in women. It remains to be seen if HRT can reduce the risk of severe COVID-19 directly, as more studies are needed.

TL;DR: Heart and circulation problems increase the risk of severe COVID-19. Estrogen is known to prevent the development of CVD. Estrogen helps regulate the immune system and promotes anti-viral activity. By contrast, male hormones can dampen the immune response.

Pregnant women, on the other hand, are at a higher risk than non-pregnant women for contracting severe COVID-19. The exact mechanism that causes pregnant women to be more susceptible is not fully understood, but current data suggests an increase in inflammation may be a factor. Statistically speaking, the risk appears to be highest in the 3^rd trimester. Complications may arise from infection, especially pre-term birth.

TL;DR: Pregnancy is a risk factor for developing severe COVID-19.

Gender roles affect exposure to the virus and virus testing rates. Approximately 70% of healthcare workers are women, which increases exposure. Caregiver roles in the household, be it caregiving for the elderly or caregiving for children, can be a strain on women who take on these roles more frequently. It can increase their exposure (i.e. having to travel to daycare, providing homecare to an aging parent) while limiting the time they have to manage their own health. Furthermore, although women tend to be more pro-active in seeking healthcare, women receive testing less often than men. Women’s symptoms are more likely to be dismissed as anxiety related issues.

TL;DR: Traditional women’s gender roles such as caregiving can increase their exposure to the virus. Gender roles can also negatively impact women’s ability to access testing.

COVID-19 has increased healthcare barriers for gender diverse individuals, as many non-emergency health services are delayed during the pandemic. Patients who are using HRT for gender affirmation require monitoring, which is conducted through bloodwork and physicals. As we try to minimize contact as much as possible, keeping up with continuous monitoring can be a challenge. Additionally, chest binding can worsen breathing difficulties cause by COVID-19. Transgender individuals who practice chest binding may want to avoid doing so until their symptoms have subsided.

TL;DR: The pandemic has made access to healthcare more challenging for gender diverse patients.

In summary, infection rates for men and women appear to be the same. The reasons for infection, such as the source of exposure, may differ between the two groups in terms of prevalence. Men experience severe COVID-19 symptoms more frequently than women and have higher mortality rates.

2. Are the COVID-19 vaccines safe during pregnancy?

There is limited data regarding the use of the new vaccines in pregnancy, but given what we do know at this point in time, the general consensus is that they are safe and effective.

The phase III clinical trials for both the Pfizer and Moderna vaccines did not include women who were pregnant at the time of recruitment, however, some participants in the trial became pregnant during the study. These individuals were few in number but did not appear to have any increased risk of miscarriage or pregnancy complications.

Furthermore, the vaccines are manufactured without any components that are known to be harmful during pregnancy. These vaccines do not contain live viral particles. Rather, the vaccine contains a bit of genetic code that allows our own cells to manufacture a non-infectious protein that triggers an immune response. This allows our bodies to fight off future infection should we be exposed.

Vaccination during pregnancy is thought to help protect the newborn against COVID-19, as antibodies produced by the mother will cross the placenta.

Side effects that are injection-related may occur, as with most vaccines. Namely, there may be tenderness or redness at the injection site. There is no reason to believe that this vaccine will cause other significant side effects for pregnant women.

3. Are the COVID-19 vaccines safe during breastfeeding?

There is currently no data suggesting that the vaccine is incompatible with breastfeeding.

4. Can mothers with COVID-19 have contact with their baby and provide childcare?

If you have tested positive for COVID-19, it is recommended to minimize your contact with the newborn as much as possible until your 14-day isolation period has concluded. We encourage mothers with COVID-19 to self isolate from the rest of the household as much as possible.

If no other caregiver is available to assist with childcare in the household, we recommend mothers take extra precautions when interacting with their baby. The caregiver who assists you should NOT be at an increased risk of contracting severe COVID-19.

You should wash your hands before and after contact with the child and wear a face mask. Wash with lukewarm water and soap for a minimum of 20 seconds. If you use hand sanitizer instead, the sanitizer should contain at minimum 60% alcohol.

5. Can mothers with COVID-19 pass the virus to their babies via breastfeeding?

Both the World Health Organization (WHO) and the Public Health Agency of Canada (PHAC) recommend that mothers who suspect they have COVID-19 or have been confirmed to have COVID-19 continue breastfeeding. The risk of transmitting the virus from respiratory droplets is considered a greater concern given our current data.

If you are feeling too ill/tired to breastfeed, it is recommended to use a pump at scheduled times to continue feeding your newborn. Using a pump at a regular schedule will help facilitate a return to the same pattern of feeding when pumping is no longer required or desired.

There is very limited data regarding possible transmission of the virus from mother to infant. Moreover, it is believed that maternal antibodies present in the milk may provide a protective benefit to the baby.

6. Can an expectant mother pass COVID-19 to her fetus?

There is conflicting data on whether or not a pregnant woman can pass the virus onto her baby. There have been small scale studies and case reports that suggest it may be possible to pass the virus in utero to the fetus. It is unknown if the virus can be passed during childbirth. Other sources suggest that evidence is lacking in robustness to conclude that the virus can be transmitted before or during childbirth. Transmission from mother to their newborn has been recorded, however, after birth. Infection of newborns is, however, rare. The best way to prevent your baby from contracting COVID-19 is through good hygiene practices and social distancing. Avoid contacts outside of the household/family and wash your hands before and after touching the baby.

7. If I am pregnant, when should I be tested for COVID-19?

Testing is only necessary if you have symptoms of COVID-19. If you start having symptoms, you should be tested as soon as possible.

8. What resources are available to help promote my health during this pandemic?

Society for Women’s Health Research: https://swhr.org/resources/coronavirus/
This website contains numerous articles about current information regarding the virus and ongoing research.

Dear Pandemic: https://dearpandemic.org/
A blog that help answer questions and concerns regarding the pandemic. The blog is maintained by an all-female group of researchers and healthcare workers.

Healthy Children: https://healthychildren.org/English/health-issues/conditions/COVID-19/Pages/default.aspx
A resource for parenting during the pandemic.

Anxiety Canada: https://www.anxietycanada.com/covid-19/
A collection of articles and tools to help manage stress and anxiety during the pandemic.

Wellness Together Canada: https://ca.portal.gs/
Resources in both English and French for Mental Health and Addictions during the pandemic.

Hope for Wellness: https://www.hopeforwellness.ca/
Online or telephone counselling sessions in a culturally aware context for Indigenous Canadians. Available in English, French, Cree, Ojibwe, and Inuktitut.

Healthy Minds App: https://hminnovations.org/meditation-app
An app for guided meditation and mindfulness, free for individuals.

References

Tadiri, C., Gisinger, T., Kautzky-Willer, A., Kublickiene, K., Herrero, M., Raparelli, V., Pilote, L. and Norris, C., 2020. The influence of sex and gender domains on COVID-19 cases and mortality. Canadian Medical Association Journal, 192(36), pp.E1041-E1045.

Bwire GM. Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women? [published online ahead of print, 2020 Jun 4]. SN Compr Clin Med. 2020;1-3. doi:10.1007/s42399-020-00341-w

Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V. COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?. Int J Mol Sci. 2020;21(10):3474. Published 2020 May 14. doi:10.3390/ijms21103474

Viveiros, A., Rasmuson, J., Vu, J., Mulvagh, S., Yip, C., Norris, C. and Oudit, G., 2021. Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones. American Journal of Physiology-Heart and Circulatory Physiology, 320(1), pp.H296-H304.

Klein, S., Flanagan, K. Sex differences in immune responses. Nat Rev Immunol 16, 626–638 (2016). https://doi.org/10.1038/nri.2016.90

Pirhadi R, Sinai Talaulikar V, Onwude J, Manyonda I. Could Estrogen Protect Women From COVID-19?. J Clin Med Res. 2020;12(10):634-639. doi:10.14740/jocmr4303

https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/for-lgbtq-patients-the-coronavirus-brings-new-challenges

Kopel J, Perisetti A, Roghani A, Aziz M, Gajendran M, Goyal H. Racial and Gender-Based Differences in COVID-19. Front Public Health. 2020;8:418. Published 2020 Jul 28. doi:10.3389/fpubh.2020.00418

https://globalhealth5050.org/the-sex-gender-and-covid-19-project/men-sex-gender-and-covid-19/

Lu-Culligan, A., Chavan, A., Vijayakumar, P., Irshaid, L., Courchaine, E., Milano, K., Tang, Z., Pope, S., Song, E., Vogels, C., Lu-Culligan, W., Campbell, K., Casanovas-Massana, A., Bermejo, S., Toothaker, J., Lee, H., Liu, F., Schulz, W., Fournier, J., Muenker, M., Moore, A., Konnikova, L., Neugebauer, K., Ring, A., Grubaugh, N., Ko, A., Morotti, R., Guller, S., Kliman, H., Iwasaki, A. and Farhadian, S., 2021. SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface.

https://www.rcog.org.uk/en/guidelines-research-services/coronavirus-covid-19-pregnancy-and-womens-health/covid-19-vaccines-and-pregnancy/covid-19-vaccines-pregnancy-and-breastfeeding/

https://dearpandemic.org/covid-19-vaccine-and-pregnancy/

https://www.cps.ca/en/documents/position/breastfeeding-when-mothers-have-suspected-or-proven-covid-19

https://dearpandemic.org/breastfeeding-and-sars-cov-2-infection/

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/pregnancy-breastfeeding.html

Cimolai N. Conflicting evidence on vertical transmission and maternal SARS-CoV-2 infection. Canadian Medical Association Journal. 2020;192(47). doi:10.1503/cmaj.76892.