Researching Through A Pandemic: Implications of Sex Discrimination in COVID-19 Research

Illustrated by Eugenia Yoh

Although there has been significant progress for women working in the fields of academia and research, significant gender inequalities still exist. Women publish fewer research papers compared to their male counterparts and are consistently less likely to be the first or last author, which are considered the most important positions [4]. With the emergence of the COVID-19 pandemic, the gender disparity in publications has only grown. Both men and women were faced with a complete reorganization of daily life; lockdowns forced parents and nonparents alike to transform their living space into a working space. However, the burden of caretaking, homeschooling and other familial responsibilities predominantly fell on women, undoubtedly impacting their ability to work and publish [4]

This phenomenon has led to a significant decrease in female authorship over studies relating to COVID-19. Ana-Caterina Pinho-Gomes, a cardiothoracic surgeon and fellow at the George Institute for Global Health at Oxford University, led a study entitled “Where Are The Women?” She concluded that women represented only 34% of all authors of COVID-19-related papers published on PubMed since the beginning of the outbreak in January of 2020. The implications for this low representation of female authorship are profound, as it “tends to create under-representation of issues that are relevant to women in research – in our current situation this may create important gaps in our understanding of COVID-19” [4]. Women researchers are more likely to report on gender and sex-disaggregated data in their publications, separating data and conclusions based on sex [4]. Insufficient female representation in COVID-19 authorship has led to a decrease in studies which compare the distinct impacts of the virus on men and women. In her article on how sex discrimination in research may be preventing a cure for COVID, health law professor Lori Andrews stated “the fact that, in 2020, researchers would blindly assume women’s bodies behave like men’s is troubling” [1]. While women researchers assuming the role of reporting gender and sex-disaggregated data is a positive thing, this unequal distribution has led to a culture in which it has become women’s responsibility to document sex-based differences in disease.

Dr. Akiko Iwasaki, professor of Immunobiology and Molecular, Cellar and Development Biology at Yale University, led an investigation of how sex impacts the immune response to COVID-19 [5]. Her research was prompted by data which indicated that the virus impacts men more severely [5]. Iwasaki found that the risk of death in males was about 1.7 times greater than that of females, a phenomenon which is not unique to COVID-19 [5]. The male sex is often associated with weaker immune responses and greater susceptibility to viral infection, having higher viral loads for Hepatitis B and HIV [5]. In her study, Iwasaki found that men had higher levels of cytokine proteins, specifically IL-8 and IL-18, released during early stages of infection with COVID-19 compared to women [5]. Cytokines are important in signaling immune cells to sites of infection. However, an excessive amount of cytokines, called a “cytokine storm,” can cause a fluid buildup in the lungs, leading to decreased oxygen levels and potential tissue damage or shock [2]. Earlier concentrations of cytokines in men’s plasma make the potential of a cytokine storm more likely. Iwasaki found that women had greater levels of T cell activation as part of their immune response. T cells are white blood cells critical to the immune response, as they are directly responsible for invading and eliminating viruses [5]. While women’s levels of T cells remained high across age groups, older male patients had a significantly lower T cell response. Iwasaki claims that the presence of two X chromosomes in women give them an advantage in immune response, as many immune-related genes are located on the X chromosome, potentially enhancing protection [5]. Moreover, the female sex hormone estrogen has been proven to perform a protective role, while male androgen receptors are known to be immunosuppressive [5]. Overall, Iwasaki’s study was crucial in revealing the many ways in which women and men’s bodies differ in their immune response to COVID-19. Her findings underscore the importance of sex-disaggregated data: the profound sex-differences in the COVID-19 immune response must be considered in order to gain a holistic understanding of the virus. 

The lack of consideration of sex-differences in scholarship had a tangible impact on women’s reactions to the vaccines. Worldwide, women have reported much worse side effects after COVID-19 vaccinations compared to men. In a study done by the CDC from the first 13.7 million COVID-19 vaccine doses given to Americans, 71.9% of the reported side effects came from women despite only 61.2% of the recipients being women [3]. Moreover, all 19 of the people who experienced anaphylactic responses to the Moderna vaccine were women, and 44 out of the 46 people who had anaphylactic reactions to the Pfizer vaccine were women [3]. Although some have suggested that women are simply more likely to report symptoms than men, there is certainly a biological underpinning for the extreme disparity in men and women’s reactions. Dr. Sabra Klein, microbiologist and immunologist at Johns Hopkins Bloomberg School of Public Health, claimed that “side effects were not sufficiently separated and analyzed by sex… and they did not test whether lower doses might be just as effective for women but cause fewer side effects” [3]. Dr. Klein cites many of the same biological explanations for women’s greater immune response to COVID-19 as Dr. Iwasaki, including sex hormones and sex chromosomes. Failure to recognize and appreciate sex-differences in the creation of the vaccine has created a condition in which women are taking a greater risk when they receive the vaccine. 

On April 13, federal health agencies and vaccine authorities called for the halt in distribution of Johnson & Johnson COVID-19 vaccinations after six people developed rare blood clotting disorders shortly after receiving the vaccination. All six of the recipients were women between the ages of 18 and 48 [6]. While the cause of this reaction is unknown thus far, according to a New York Times article released on April 13, “Government experts are concerned that the blood clots are linked to an immune response triggered by the vaccine” [6]. Women are experiencing more extreme reactions to Pfizer, Moderna and Johnson & Johnson COVID-19 vaccinations, a phenomenon which could have potentially been prevented or mitigated had there been more research on the distinct ways in which women and men’s immune responses to COVID-19 differ. 

Male-centric research presents a real danger to the progression of our vaccinations and search for possible cures for COVID-19. Dr. Iwasaki’s findings suggest that different treatments for men and women might be necessary. However, without scientific reports which disaggregate symptoms by sex, we will continue to operate under the false assumption that men and women respond identically to the virus. Addressing sex discrimination in medical research is not only critical to achieving health justice, but will also benefit the longterm health of both women and men. 

Edited by: Haleigh Pine
Illustrated by: Eugenia Yoh


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