Women’s Health Research at Yale today announced funding for a unique study focusing on sex differences in immune responses to SARS-CoV-2, the virus which causes COVID-19.

Current reports from the United States, Italy, and China indicate that men are likely to suffer more severe cases and die of COVID-19 than women. In Italy, one analysis showed 70 percent of deaths from the illness were men. Extensive prior research has revealed significant differences in the immune systems of women and men.

“Uncovering the biology of these sex differences can reveal very important clues about the underlying mechanisms of a disease,” said WHRY Director Carolyn M. Mazure, Ph.D. “A detailed understanding of the dynamics of immune responses to SARS-CoV-2 is dramatically needed, and studies seeking to understand the apparent sex differences in response to the virus are crucial.”

Dr. Akiko Iwasaki, Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellar and Development Biology in collaboration with Dr. Aaron Ring, an Assistant Professor of Immunobiology, will examine sex differences in immune response to SARS-CoV-2. Using blood drawn from male and female patients infected with the virus, Dr. Iwasaki will analyze the complex interaction of immune cells and antibodies throughout the course of the disease and how this influences health outcomes.

Non-infected (control) subjects will be compared to patients with COVID-19 and followed over time so if they become infected, Iwasaki’s laboratory can investigate the changes that occur in response to the virus. In severe cases, such changes include excessive levels of inflammatory proteins called cytokines that lead to life-threatening fluid buildup in the lungs following what physicians refer to as a “cytokine storm.”

This study will offer new insights into the body’s immune responses that are needed to develop targeted vaccine strategies and therapeutic approaches. In addition, the study aims to provide a panel of biomarkers for predicting the efficacy of each possible treatment option.

Women account for 75 percent of all U.S. cases of autoimmune disease, in which the body attacks itself instead of intended foreign targets such as disease-causing viruses and bacteria. In addition, antibody responses to seasonal influenza vaccines are consistently at least twice as strong in women than men. Although sickness and death during previous influenza outbreaks and pandemics are often higher for women than men, it remains unclear why COVID-19 has shown the opposite pattern.

“The scale of this study is unmatched by any other announced studies using human blood samples,” said Iwasaki, an elected member of the National Academy of Medicine and the National Academy of Sciences. “Understanding how the innate and adaptive immune systems in women and men contribute to defense against SARS-CoV-2 infection as well as shape the entire COVID-19 disease manifestation is critical if we are to develop specific treatments that decrease excessive inflammation and promote long-lasting immunity that can extinguish this pandemic.”