Long COVID can cause substantial economic loss and missed days of work, and it can strike women more often than men—possibly because women have increased expression of an RNA gene implicated in autoimmunity—according to two new studies.
Billions in economic loss
In the first long-COVID study, published this week in BMJ Open, British researchers estimate that the chronic condition improved only incrementally, and most patients continued to report lost days of work 6 months after enrolling in specialty long-COVID clinics.
Long-COVID has been known to significantly diminish [the] quality of life, increase disability, and result in economic loss in workdays lost to illness. In the United Kingdom, researchers looked at outcomes in 35 specialized long-COVID clinics among 4,087 patients diagnosed as having long-COVID from August 2020 to August 2022.
All patients were enrolled in the rehabilitation program Living With Covid Recovery (LWCR), an app that collects patient symptoms and uses that information to deliver tailored advice. The app also has a dashboard that allows clinicians to review patients’ progress and communicate with them, among other features, the authors said.
The patients were assessed using the Work and Social Adjustment Scale (WSAS), whereby scores of 20 higher indicate moderately severe limitations. Patients had a mean age of 47.3 years, and 94% were in the working-age bracket of 18 to 65 years. The participants were 71% female and 89% White.
The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% confidence interval, 18.6 to 19.6), with 46% of the participants reporting a WSAS score above 20 (moderately severe or worse impairment). Fully 72% of patients who reported [a] loss of working days when they first started using the app and continued to use it, also reported working days lost at 6 months. And 36% of them were unable to work at all.
The researchers also determined that the monthly societal cost per patient of long COVID at 6 months was £931 ($1,174 US), mostly driven by the costs tied to lost working days.
Even if only 10% of all long Covid patients in the UK were significantly impaired, that would equate to £2billion [$2.5 billion US] per year.
“Obviously patients in our sample are likely to be more symptomatic and/or impaired than the average long Covid patient, but even if only 10% of all long Covid patients in the UK were significantly impaired, that would equate to £2billion [$2.5 billion US] per year,” said senior study author Manuel Gomes, PhD, in a press release from the University College London.
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Women’s immune systems may explain long-COVID differences
Men may be more prone to severe symptoms of COIVD-19 in the acute phase, but women are more likely to report long-COVID, according to a meta-analysis published in 2022 that reported a pooled estimated odds ratio of 1.57 (57% higher risk) for women developing long COVID than men.
Now researchers have used data collected from 45 patients who were recruited at 3 months after infection to study recovery from SARS-CoV-2 infection, and they write in a study this week in Science Translational Medicine that SARS-CoV-2 could trigger overactive gene expression in women that leads to persistent symptoms.
Of the 36 participants in the study who developed long COVID at 3 months after infection, 55.6% were female, the mean age was 43.0 years, and 8 participants (22.2%) were previously hospitalized for acute SARS-CoV-2 infection. At 3 months after infection, 9 participants had fully recovered, and 44.4% were women, the mean age was 41.7 years, and one participant was previously hospitalized for acute SARS-CoV-2 infection.
Banked peripheral blood mononuclear cell samples were taken from participants during initial illness, 3 months after infection, and at 12 months after infection.
The investigators noted a difference in male and female cell-to-cell communication patterns, with women showing an expression of several genes that encode proteins involved in inflammation. In particular, the RNA gene XIST, which has previously been implicated in autoimmunity, was more highly expressed in several immune cell subsets during acute infection in women who subsequently developed long COVID.
The authors said these findings could guide future research and help tailor long COVID assessments and treatments.
