• Marco Floridia, Marina Giuliano, Liliana Elena Weimer, Maria Rosa Ciardi, Piergiuseppe Agostoni, Paolo Palange, Patrizia Rovere Querini, Silvia Zucco, Matteo Tosato, Lo ForteAldoADepartment of Multidimensional Medicine, Internal Medicine Unit, San Giovanni Di Dio Hospital, Florence, Italy., Paolo Bonfanti, Donato Lacedonia, Emanuela Barisione, Stefano Figliozzi, Paola Andreozzi, Cecilia Damiano, Flavia Pricci, Graziano Onder, and I. S. S. Long-COVID Study Group.
• National Center for Global Health, Istituto Superiore Di Sanità, Rome, Italy. marco.floridia@iss.it.
• Bmc Med. 2024 Nov 14; 22 (1): 532532.

BackgroundLong-COVID symptoms remain incompletely defined due to a large heterogeneity in the populations studied, case definitions, and settings of care. The aim of this study was to assess, in patients accessing care for Long-COVID, the profile of symptoms reported, the possible clustering of symptoms and cases, the functional status compared to pre-infection, and the impact on working activity.MethodsMulticentre cohort study with a collection of both retrospective and prospective data. Demographics, comorbidities, severity and timing of acute COVID, subjective functional status, working activity and presence of 30 different symptoms were collected using a shortened version of the WHO Post COVID-19 Case Report Form. The impact on working activity was assessed in multivariable logistic regression models. Clustering of symptoms was analysed by hierarchical clustering and the clustering of cases by two-step automatic clustering.ResultsThe study evaluated 1297 individuals (51.5% women) from 30 clinical centres. Men and women had different profiles in terms of comorbidities, vaccination status, severity and timing of acute SARS-CoV-2 infection. Fatigue (55.9%) and dyspnea (47.2%) were the most frequent symptoms. Women reported more symptoms (3.6 vs. 3.1, p < 0.001), with a significantly higher prevalence of memory loss, difficult concentration, cough, palpitation or tachycardia, dermatological abnormalities, brain fog, headache and visual disturbances. Dyspnea was more common in men. In the cluster analysis of the 19 more common symptoms, five aggregations were found: four two-symptom clusters (smell and taste reduction; anxiety and depressed mood; joint pain or swelling and muscle pain; difficult concentration and memory loss) and one six-symptom cluster (brain fog, equilibrium/gait disturbances, headache, paresthesia, thoracic pain, and palpitations/tachycardia). In a multivariable analysis, headache, dyspnea, difficult concentration, disturbances of equilibrium or gait, visual disturbances and muscular pain were associated with reduced or interrupted working activity. Clustering of cases defined two clusters, with distinct characteristics in terms of phase and severity of acute infection, age, sex, number of comorbidities and symptom profile.ConclusionsThe findings provide further evidence that Long-COVID is a heterogeneous disease with manifestations that differ by sex, phase of the pandemic and severity of acute disease, and support the possibility that multiple pathways lead to different clinical manifestations.© 2024. The Author(s).

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