Long COVID: key risk factors in postmenopausal women

After contracting COVID-19, regardless of severity, some individuals experience symptoms that persist for months. This prolonged illness is often referred to as long COVID or post-COVID-19 syndrome and is sometimes called post-acute sequelae of SARS-CoV-2 (PASC). Currently, there is no universally accepted definition of long COVID. However, various health organizations have put forward working definitions. The World Health Organization (WHO) defines long COVID as symptoms that develop within three months of a confirmed or probable COVID-19 infection and last for at least two months. While common symptoms of long COVID can include fatigue, brain fog, memory problems, shortness of breath, joint and muscle pain, and sleep disturbances, exact symptom lists, criteria and timelines can differ across studies and guidelines. According to WHO, over 200 different symptoms have been reported. These symptoms can affect multiple organ systems and often interfere significantly with daily life.

The risk factors for long COVID are not fully understood, but emerging research suggests that several factors may increase a person’s likelihood of developing the condition. These include older age, being female, experiencing a more severe acute phase of COVID-19 and pre-existing health conditions such as a compromised immune system, obesity, asthma, or cardiovascular disease. However, the mechanisms driving long COVID remain unclear, and more research is needed to identify the factors that predispose certain individuals to this debilitating condition.

A recent study published by Fred Hutch researchers in Annals of Epidemiology, explores these risk factors in a specific population—postmenopausal women. This demographic is particularly important to study, as older adults are generally more vulnerable to the long-term effects of COVID-19. The study draws on data from the Women’s Health Initiative (WHI), a large-scale study on women’s health in the United States. The WHI’s comprehensive dataset, collected over three decades, allowed researchers to explore long COVID in detail, analyzing how various health and lifestyle factors contribute to the condition in postmenopausal women.

Dr. Marian Neuhouser, the Head of Fred Hutch’s Cancer Prevention Program and lead author of the study, emphasized the significance of using the WHI dataset to explore long COVID. “Long COVID remains a serious health problem for many,” she said. “Many prior studies on long COVID use cross-sectional data. Since the WHI has robust health history, demographic, and lifestyle data going back more than 30 years, we were able to leverage this vast data resource using novel machine learning to identify potential risk factors for long COVID in older women.” The study included more than 1,230 postmenopausal women who had been diagnosed with COVID-19, of whom 425 reported experiencing long COVID symptoms. Common symptoms among this group included fatigue, brain fog, memory issues, and musculoskeletal pain. Dr. Neuhouser and her team employed machine learning techniques to identify the top 20 risk factors associated with long COVID in this group, which were further analyzed using statistical models.

 The study found that women who had experienced significant weight loss in the two years before their COVID-19 diagnosis were at a higher risk of developing long COVID. In addition, those with mobility issues, such as difficulty bending, kneeling, or needing assistive devices like canes or walkers, were also more likely to suffer from long COVID. Certain pre-existing health conditions, including a history of rheumatoid arthritis, heart valve procedures, and sleep disturbances, were found to increase the likelihood of long COVID. Interestingly, while older age is typically thought to be associated with more severe outcomes, in this cohort, it was linked to a lower probability of long COVID diagnosis. In contrast, factors such as recent weight loss and physical limitations increased the risk.

These findings have important implications for public health, particularly in how we manage the long-term effects of COVID-19 in older populations. Dr. Neuhouser highlighted that these findings open new avenues for clinical practice and future research. “Clinicians may be able to use the information to identify patients who could be at risk for long COVID,” she noted. She further pointed out that a natural next step for research would be to “build a risk prediction model,” which could help doctors more effectively screen and manage patients at risk for long COVID. Such a model would enable healthcare providers to identify vulnerable individuals early and potentially intervene before long COVID symptoms become debilitating.

The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, and the U.S. Department of Health and Human Services. The WHI Clinical Coordinating Center is housed at Fred Hutch. Additional support was provided by the National Center for Advancing Translational Sciences (NCATS). Administration of the COVID surveys to WHI participants was aided by an Andy Hill Care Fund grant.
 

Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium members Drs. Marian Neuhouser and Holly Harris contributed to this study.

Neuhouser, M. L., Butt, H. I., Hu, C., Shadyab, A. H., Garcia, L., Follis, S., Mouton, C., Harris, H. R., Wactawski-Wende, J., Gower, E. W., Vitolins, M., Von Ah, D., Nassir, R., Karanth, S., Ng, T., Paskett, E., Manson, J. E., & Chen, Z. 2024. Risk factors for long COVID syndrome in postmenopausal women with previously reported diagnosis of COVID-19. Annals of epidemiology, 98, 36–43.