Females have a 31% higher risk of developing Long Covid

Females have a 31 per cent higher associated risk of developing Long Covid, with women aged 40 to 55 years having the highest propensity, according to a new study.

The study followed 12,276 participants over time to identify the risk of developing Long Covid, and found females with a “risk ratio” of 1.31 compared with males, equating to 31 per cent higher associated risk.

This was even when considering factors like race, ethnicity, Covid variant, severity of Covid infection and other non-medical social factors that affect health.

The risk among females for developing long Covid was dependent on age, pregnancy and menopausal status.

“These findings show that patients and health care teams should consider the differences in long COVID risk as it relates to sex assigned at birth,” said Dimpy Shah,  assistant professor of population health sciences at UT Health San Antonio.

“Understanding these differences can help us recognise and treat patients with Long Covid more effectively.”

“This important study from the RECOVER cohort identifies risk factors for long COVID that are critical in providing insights for prevention and treatment of this often debilitating disease,” said Thomas Patterson, professor of medicine at UT Health San Antonio.

Largest cohort study for Long Covid

Worldwide, SARS-CoV-2, a strain of coronavirus that causes Covid-19, has infected more than 700 million people, with an estimated seven million deaths, the study notes. Although many individuals recover from acute Covid-19, a substantial portion experience long-term effects, called Long Covid, or post-Covid condition.

Other post-viral and autoimmune conditions have a female predominance, but whether the same is true for Long Covid, especially within different subgroups, has been uncertain.

Numerous studies had shown that males have more severe acute Covid-19 cases and higher mortality than females. However, emerging literature suggested that females may be at greater risk for new and persisting symptoms following initial infection.

Studies had yet to fully account for factors that may distort the true estimate of biological sex-related risk – like age, menstrual status, comorbidities, vaccination status, variants of concern, severity of acute illness and differential engagement in health care. Some studies relied upon relatively small sample sizes or those lacking ethnic or racial diversity.

The RECOVER researchers set out to evaluate sex differences in the risk of developing Long Covid among adults with SARS-CoV-2 infections, accounting for distorting factors and representing the largest cohort to date followed up in a natural history study of Long Covid.

Data was examined from participants who had a qualifying study visit six months or more after their initial Covid-19 infection. Gender was defined as self-reported sex assigned at birth.

The scientists measured development of Long Covid using a self-reported symptom-based questionnaire and scoring guideline at the first study visit. They used propensity score matching to estimate risk ratios and risk differences.

The full model included demographic and clinical characteristics, and social determinants of health, with a reduced model including only age, race and ethnicity.

The full model found the 31 per cent higher risk for females, with a mean age of infection at 46 years. Among participants aged 40 to 54 years, the risk was even higher – at 42 per cent higher in menopausal participants and 45 per cent higher in non-menopausal female participants, compared with male participants.

“This study gives us new knowledge and builds on other studies that also looked at sex assigned at birth and Long Covid,” Shah said.

“Because of the size of the RECOVER study and the diversity of participants, we had a special opportunity to look at sex assigned at birth while also considering things like vaccination status, autoimmune disease, diabetes, BMI and Covid variant.

“We hope this encourages other researchers to explore why there are differences in the risk of developing Long Covid based on your assigned sex at birth,” she said.