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Sex & Gener in EM Sex and Gender Differences in COVID-19
Sex and Gender Differences in COVID-19
By Lily Gordon on behalf of the SAEM Sex & Gender in Emergency Medicine Interest Group Case Overview
This case study follows the clinical courses of two individuals suffering from COVID-19 with the goal of understanding how sex and gender impact clinical presentation and outcomes. Each case is composite narrative based on the known patterns of risk factors, clinical presentation, and disease course in cisgender men and women.
Patient Information
Name: Elijah Cooper Age: 55 Sex: Male Occupation: Real estate agent
Chief Complaint
Confusion with associated cough and fever
History of Present Illness
Elijah noticed that he was starting to feel fatigued about seven days ago. He went to sleep and woke up the next morning with a low-grade fever. Over the next four days he developed a dry cough and his fever persisted, hovering between 100-101 degrees. This morning his wife noticed he seemed confused and took him to the ED.
Past Medical and Social History
Elijah has a past medical history of diabetes and hypertension. He is a current smoker with a 20 pack a year history. He doesn’t drink alcohol.
Diagnosis
Work-Up and Clinical Course
Elijah’s pulse oximeter reads 88%. His CXR shows bilateral ground-glass opacities in the lower lung lobes. Elijah is started on supplemental oxygen via nasal canula and dexamethasone in the ED. He is quickly admitted to the ICU where he is also given a single dose of Tocilizumab. Over the next 12 hours Elijah develops hypercapnia and the decision to intubate is made on day one of his hospitalization. Elijah is extubated on day 10 of his hospitalization and eventually discharged on day 15.
Patient Information
Name: Olivia James Age: 39 Sex: Female Occupation: Elementary school teacher
Chief Complaint
Dyspnea and fatigue
History of Present Illness
Olivia noticed her food tasted odd about 8 days ago. She went into work that day, and by the end of the day had a throbbing headache and muscle pains. Olivia was concerned and got a rapid COVID test that evening and tested positive. She spent the next five days in quarantine, but her symptoms did not subside. Yesterday she started to feel as though she couldn't quite catch her breath while going upstairs and decided to come into the emergency department today.
Past Medical and Social History
Olivia does not have any active medical conditions. She is overweight with a BMI of 30. She does not smoke and has 1-2 drinks of alcohol on the weekend with friends.
Diagnosis
Work-Up and Clinical Course
Olivia’s CXR shows consolidation in the peripheries of the lower lungs bilaterally. She had an SaO2 of 94%. She is put on a high flow nasal canula and started on oral dexamethasone. She is admitted to the hospital and spends three days on supplemental oxygen before being discharged.
As of August 2021, the Centers for Disease Control has documented over 30 million cases of COVID-19 in the United States with 52% of cases attributed to women. Despite the slightly higher rates of infection among women, men account for 54.8% of COVID-19 related deaths and 60.6% of ICU admissions. Few countries are reporting gender or sex disaggregated data, but preliminary reports suggest that this trend is reflected on a global scale.
Studies have documented significant differences in the initial presentation of COVID-19 in cisgender men and women. For example, cisgender women are much more likely to present with anosmia, dysgeusia, and headache. Additionally, on initial presentation, men generally had more severe disease based on respiratory parameters and laboratory parameters.
The disparities in outcomes and presentations between men and women are likely due to a combination of sex-specific biological as well as gender-related social differences. Sexbased differences in immunological and inflammatory responses have long been recognized in the scientific literature. Sex hormones play a role in both the adaptive and innate immune responses, with testosterone having an overall immunosuppressive effect while estrogen has an upegulating effect on the immune system. As a result, cisgender women generally have faster rates of viral clearance and disease resolution as compared with cisgender males.
Previous research has also shown that females display higher rates of adaptive immune response, which results in higher levels of antibody production and longer immune memory. Persistence of higher antibody levels in cisgender women as compared with men has been observed in cases of COVID-19, which may have implications for sex-dependent vaccine efficacy in the future. With regards to inflammatory responses, studies have identified a link between high levels of inflammatory cytokines, such as Il-6 and TNF-alpha, and the acute phase reactant C-Reactive Protein with more severe SARS-CoV-2 disease and death. Males with COVID-19 show higher levels of CRP, Il-6, and TNF-alpha levels independent of comorbidities such as diabetes, hypertension, and smoking history.
Among women, pregnant individuals are of particular concern for high-risk COVID-19 and complications. Although preliminary data does suggest higher rates of infection among pregnant compared with nonpregnant cisgender women, it is unclear whether this finding reflects a true difference in infection rates or a difference in testing rates as a result of pregnant women’s increased contact with the health care system. Overall, current data suggest that pregnant women have slightly higher rates of ICU admission and mechanical ventilation, but there is no significant difference in the mortality rate based on pregnancy status.
Biological sex is not the only contributor to the differential outcomes observed between men and women. Gender roles and expectations have major impacts on exposure to risk factors for both men and women. Observational studies have consistently demonstrated that cisgender women have higher rates of health care seeking behavior for physical and mental health concerns.
Additionally, women are much more likely to work in health care or other first-line jobs such as grocery stores and childcare, thus increasing their potential for viral exposure. Furthermore, cisgender men have higher rates of smoking, diabetes, and hypertension, which likely contribute to an overall increased modifiable burden of COVID-19 in men.
Although cisgender individuals make up most of the population, transgender and gender nonconforming individuals are at particularly high risk for severe COVID-19 due to specific social determinants of health that impact this population. Approximately 1-2% of people identify as either transgender or gender nonconforming. There is a dearth of data on the impact of COVID-19 on transgender and gender nonconforming individuals. Nevertheless, transgender individuals are much more likely to live below the poverty line and to be uninsured, both of which are associated with more severe COVID-19. Additionally, transgender and gender non-conforming people experience high rates of discrimination in health care settings, making them less likely to seek medical care.
Throughout the coronavirus pandemic, sex and gender have impacted the health outcomes for individuals on a global scale. We have yet to fully understand the nuances of these impacts, particularly with regards to pregnancy and the interplay of gender and healthcare access. Further research on the differences in COVID presentation, as well as its clinical progression, focusing on the intersection of sex, gender, and COVID-19 outcomes is greatly needed to fully understand the underpinnings of the existing disparities. Furthermore, such research could allow for the development of clinical algorithms that stress differential triaging of men based on their higher degree of risk as well as tailored interventions based on sex-based biological differences.
ABOUT THE AUTHOR
Lily Gordon is a medical student at Warren Alpert Medical School, Brown University, and a research assistant at the Brown University School of Public Health.
About SGEM
The Sex and Gender in Emergency Medicine (SGEM) Interest Group works to raise consciousness within the field of emergency medicine on the importance patient sex and gender have on the delivery of emergency care and to assist in the integration of sex and gender concepts into emergency medicine education and research. Joining SGEM is free! Just log into your member profile. Click “My Account” in the upper right navigation bar. Click the “Update (+/-) Academies and Interest Groups” button on the left side. Select the box next to the academy you wish to join. Click “save.”
