A large study led by the University of Texas Health Science Center at San Antonio shows that women infected with SARS-CoV-2 are more likely to go on to develop long COVID than men.
Writing in JAMA Network Open, first author Dimpy Shah, MD, PhD, an assistant professor at UT Health San Antonio, and colleagues from the RECOVER Consortium report that overall female sex increased the risk of developing long COVID from 31–44%.
When broken down by age groups, this association was stronger in women over the age of 40. It was also influenced by menopause and pregnancy status, with non-pregnant and non-menopausal women being at higher risk for long-COVID than pregnant or menopausal women.
“Numerous studies have shown that males have more severe acute COVID-19 cases and higher mortality than females,” explain the authors. “However, emerging literature suggests that females may be at greater risk for new and persisting symptoms following SARS-CoV-2 infection.”
Based on these indications, Shah and colleagues carried out a study of 12,276 individuals who experienced SARS-CoV-2 infection and are enrolled in the Researching COVID to Enhance Recovery (RECOVER) cohort. This cohort was set up as part of the RECOVER consortium research efforts and includes people who were infected with the SARS-CoV-2 virus both before and after enrollment.
The average age of study participants was 46 years on enrollment and 73% were female. The study population is 57% White, 18% Hispanic, 14% Black, 6% Asian and 5% multiracial, listed as “other” or missing data.
Participants were classified as having long COVID if they had symptoms a minimum of six months after their first infection based on a scoring algorithm. Long COVID symptoms included: post exertional malaise, fatigue, brain fog, dizziness, palpitations, loss of or change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and snoring or sleep apnea.
The results showed female sex was associated with long COVID onset in two separate models with a 31% and 44% increased risk compared with men in the two models. When the cohort was divided by age, women aged 18–39 years had a nonsignificant 4% increase in risk compared with men of a similar age. However, women aged 40–54 years were at significantly increased risk with non-menopausal women in this group having a 45% increased risk and menopausal women a 42% increased risk versus men of a similar age.
Pregnancy seemed to have a protective effect, as when pregnant women were excluded from the analysis, the increased risk for long COVID associated with female sex was 50%.
The authors acknowledge that their study had some limitations, for example, lack of information about sex hormone levels or use of hormone-related medication, a lack of a control group and uncertainty about differences in reporting of symptoms between women and men in the study.
However, they conclude that “these findings highlight the need to identify biological mechanisms contributing to sex specificity to facilitate risk stratification, targeted drug development, and improved management of long COVID.”
“Understanding the mechanisms of sex differences can provide preventive and management strategies for not only long COVID but also other post-viral illnesses,” they added.
