Women are more likely than men to suffer from long COVID

The research on gender-specific differences in symptoms and abnormalities that persist following acute COVID-19 reveal that women are more likely to suffer from the long COVID-19 syndrome than their male counterparts.

More than two years after the global COVID-19 pandemic, it is clear that infection with severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) can lead to a new disease called post-acute COVID syndrome or long COVID. Recent studies have identified subdivision of long COVID on subacute or persistent symptomatic COVID-19, which includes symptoms and abnormalities that persist for 4 to12 weeks following acute COVID-19, and chronic or post-COVID-19 syndrome, which includes symptoms and abnormalities that persist for more than 12 weeks following acute COVID-19.

Symptoms of long COVID can last for several months or longer. Patients with long COVID suffer from a wide range of organ dysfunctions and clinical symptoms. Neurological and neuropsychiatric symptoms are the most frequent, persisting and disabling.

About the studies

A recently published observational study from Canadian authors analyzed the neuropsychological and neuropsychiatric functioning in 97 patients with prior SARS-CoV-2 infection and persistent cognitive disorders. The study assessed the effects of gender and age on COVID-19 symptoms and outcomes, as well as the influence of the acute ilness presentation (retrospectively assessed) on persistent neurological and neuropsychological symptoms.

Results showed that men had higher rates of hospitalization than women during the acute COVID-19 illness. Abnormal findings on post-COVID cognitive testing were associated with older age and the presence of “brain fog” during the acute illness.

However, the female gender was the only predictor associated with persistent deficits in executive functions and neurological symptoms (headaches, vertigo, visual and hearing impairments, fatigue, tremor, etc.).

In addition, female gender and shortness of breath during acute illness were found to be a risk factors for more persistent short-term memory symptoms. Notably, an early multicentre cohort study by Sigfrid L, et al that evaluated the long COVID symptomes found that women under the age of 50 years were seven times more likely to become more breathless than men of the same age.

According to the authors, these findings provide additional evidence that women are more vulnerable to the prolonged effects of SARS-CoV-2 infection. The increased incidence of neuropsychiatric symptoms in patients with long COVID remains an area of concern for which further research is needed.

Vasilevskaya A, et al. Sex and age affect acute and persisting COVID-19 illness. Sci Rep 2023; 13, 6029. (Open Access)

A prospective cohort study by Bai F, et al explored the relationship between female gender and long COVID symptoms in 260 patients.

The most commonly reported symptoms were fatigue (40%), dyspnoea (29%), musculoskeletal pain (21%) and “brain fog” (20%). Anxiety symptoms were found in 19% of individuals, depression in 11% of patients, and post-traumatic stress disorder was reported in one-third of patients.

In multivariable logistic regression analysis, the female gender was associated with a three-fold higher risk of long COVID after adjustment for age, disease severity, comorbidities, smoking, BMI and time between onset of symptoms and virological clearance.

Other independent predictors of long COVID were older age and active smoking. The severity of the disease and the time to virological clearance were not associated with long COVID at univariable and multivariable analyses.

The authors suggested that gonadal steroids and increased production of IgG antibodies in females in the acute phase of the disease could play a role in perpetuating the hyper-inflammatory status after recovery.

Bai F et al. Female gender is associated with the long COVID syndrome: a prospective cohort study. Clin Microbiol Infect. 2022 Apr; 28(4): 611.e9–611.e16. (Open Access)

The review article from Sylvester SV et al discussed the differential effect of gender on the long COVID-19 syndrome.

Results showed that female patients were more likely to suffer from the long COVID syndrome than their male counterparts, and this trend was observed in all nine studies included in the review. In addition, gastrointestinal, psychiatric, dermatological, neurological, rheumatological and other complications were significantly more likely in female patients with the long COVID syndrome than in their male counterparts.

However, endocrine and renal complications were significantly more likely to occur in male patients with the long COVID syndrome.

The authors suggested that differences in immune system function between genders could be a major driver of gender differences in long COVID syndrome. They also emphasized the role of gonadal steroids.

Sylvester SV et al. Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review. Curr Med Res & Opin 2022; 38:8, 1391-1399. (Open Access)