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Among patients who developed post-acute COVID-19 -- so-called "long COVID" -- almost one-third reported clinical features of fibromyalgia, Italian researchers reported.

In a web-based survey that included more than 600 patients, 30.7% met the American College of Rheumatology criteria for a fibromyalgia diagnosis at a mean of 6 months after having had COVID-19, said Francesco Ursini, MD, PhD, of the University of Bologna, and colleagues.

"In light of the overwhelming numbers of the SARS-CoV-2 pandemic, it is reasonable to forecast that rheumatologists will face a sharp rise in cases of a new entity that we defined as 'FibroCOVID,'" the researchers wrote online in .

Aside from the potentially lethal acute viral infection of SARS-CoV-2, a post-acute syndrome with myriad symptoms including not only pulmonary sequelae but also endocrine, cardiovascular, neuropsychiatric, and musculoskeletal manifestations is now widely recognized.

The current definition of fibromyalgia requires a score of 13 or higher on the Fibromyalgia Symptom Scale, which combines scores on the Widespread Pain Index and Symptom Severity Scale.

The pathogenesis of fibromyalgia is not completely understood. "Pain augmentation/dysperception seems associated with exquisite neuromorphological modifications and imbalance between pronociceptive and antinociceptive pathways arising from an intricate interplay between genetic predisposition, stressful life events, psychological characteristics, and emerging peripheral mechanisms, such as small fiber neuropathy or neuroinflammation," Ursini and colleagues explained.

In addition, viral triggers have been linked with the development of fibromyalgia. Therefore, to investigate the prevalence of fibromyalgia following acute COVID-19, the researchers conducted a cross-sectional survey during April 2021, in which participants completed a survey that included information on demographics, symptoms and duration of COVID-19, and comorbidities.

A total of 616 patients were included, with 189 diagnosed with fibromyalgia. More than three-quarters were women whose mean age was 45. Median duration of acute COVID-19 was 13 days, and 10.7% were hospitalized. Among the symptoms reported during the acute viral illness were anosmia/ageusia in 70.9%, myalgia in 70.4%, fever in 67.7%, and arthralgia in 64.6%.

Comorbidities included anxiety and chronic pulmonary disease in patients both with and without fibromyalgia. In contrast, hypertension was significantly higher among fibromyalgia patients (27% vs 10.8%, P<0.0001), as was mean body mass index (30.4 vs 23, P<0.0001) and the prevalence of obesity (49.2% vs 2.1%, P<0.0001).

Among the survey respondents who had fibromyalgia, 57% were women, a percentage that was lower than the 77.4% of women in the cohort overall, suggesting that men more often developed the musculoskeletal sequelae, the researchers explained.

Those with fibromyalgia also were significantly more likely to be hospitalized (19% vs 7%, P<0.0001). During the acute phase of disease, patients who subsequently developed fibromyalgia more often reported cough (52.9% vs 45%, P=0.046) and dyspnea (45.5% vs 35.4%, P=0.017), and also more often required supplemental oxygen (18% vs 7.5%, P<0.0001).

On univariate analysis, factors associated with fibromyalgia included age, male sex, cough, dyspnea, hypertension, obesity, and treatment with antibiotics, low molecular weight heparin, or oxygen.

On multivariate analysis, the only independent predictors were male sex, with an odds ratio of 9.951 (95% CI 6.025-16.435, P<0.0001) and obesity, with an odds ratio of 82.823 (95% CI 32.192-213.084, P<0.0001).

Overall, patients who developed fibromyalgia appeared to have a more serious phenotype of COVID-19, more often requiring hospitalization and supplemental oxygen, the researchers reported. "Notably, both male gender and obesity have been consistently associated with a more severe clinical course in patients with COVID-19, including a significantly increased mortality rate."

Potential mechanisms by which the coronavirus could trigger fibromyalgia, the team speculated, are epithelial injury or damage to the neuromusculature, immune dysfunction, and upregulation of inflammatory cytokines such as interleukins 1 and 6.

Prospective studies will be needed to further elucidate the clinical course and outcomes of the post-acute COVID-19 musculoskeletal disease manifestations, the authors cautioned.

A potential limitation of the study, they said, was the possibility of self-selection bias.

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