AUTHOR=Bellan Mattia , Apostolo Daria , Albè Alice , Crevola Martina , Errica Nicolò , Ratano Giacomo , Tonello Stelvio , Minisini Rosalba , D’Onghia Davide , Baricich Alessio , Patrucco Filippo , Zeppegno Patrizia , Gramaglia Carla , Balbo Piero Emilio , Cappellano Giuseppe , Casella Sara , Chiocchetti Annalisa , Clivati Elisa , Giordano Mara , Manfredi Marcello , Patti Giuseppe , Pinato David James , Puricelli Chiara , Raineri Davide , Rolla Roberta , Sainaghi Pier Paolo , Pirisi Mario , the No-More COVID study group , Bellan Mattia , Apostolo Daria , Albè Alice , Crevola Martina , Nicolò Errica , Ratano Giacomo , Acquavivas Antonio , Castello Luigi Mario , Tonello Stelvio , Minisini Rosalba , D’Onghia Davide , Baricich Alessio , Patrucco Filippo , Zeppegno Patrizia , Gramaglia Carla , Avanzi Gian Carlo , Balbo Piero Emilio , Baldon Giulia , Barini Michela , Battaglia Marco , Bor Simone , Cantaluppi Vincenzo , Cappellano Giuseppe , Carriero Alessandro , Casella Sara , Chiocchetti Annalisa , Cuneo Daria , Gambaro Eleonora , Giordano Mara , Isabella Luisa , Loro Alberto , Marangon Debora , Mones Emanuele , Paracchini Elena , Patti Giuseppe , Pinato David James , Puricelli Chiara , Raineri Davide , Rolla Roberta , Sainaghi Pier Paolo , Tricca Stefano , Pirisi Mario TITLE=Determinants of long COVID among adults hospitalized for SARS-CoV-2 infection: A prospective cohort study JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1038227 DOI=10.3389/fimmu.2022.1038227 ISSN=1664-3224 ABSTRACT=Rationale

Factors associated with long-term sequelae emerging after the acute phase of COVID-19 (so called “long COVID”) are unclear. Here, we aimed to identify risk factors for the development of COVID-19 sequelae in a prospective cohort of subjects hospitalized for SARS-CoV-2 infection and followed up one year after discharge.

Methods

A total of 324 subjects underwent a comprehensive and multidisciplinary evaluation one year after hospital discharge for COVID-19. A subgroup of 247/324 who consented to donate a blood sample were tested for a panel of circulating cytokines.

Results

In 122 patients (37.8%) there was evidence of at least one persisting physical symptom. After correcting for comorbidities and COVID-19 severity, the risk of developing long COVID was lower in the 109 subjects admitted to the hospital in the third wave of the pandemic than in the 215 admitted during the first wave, (OR 0.69, 95%CI 0.51-0.93, p=0.01). Univariable analysis revealed female sex, diffusing capacity of the lungs for carbon monoxide (DLCO) value, body mass index, anxiety and depressive symptoms to be positively associated with COVID-19 sequelae at 1 year. Following logistic regression analysis, DLCO was the only independent predictor of residual symptoms (OR 0.98 CI 95% (0.96-0.99), p=0.01). In the subgroup of subjects with normal DLCO (> 80%), for whom residual lung damage was an unlikely explanation for long COVID, the presence of anxiety and depressive symptoms was significantly associated to persistent symptoms, together with increased levels of a set of pro-inflammatory cytokines: interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12, IL-1β, IL-17. In logistic regression analysis, depressive symptoms (p=0.02, OR 4.57 [1.21-17.21]) and IL-12 levels (p=0.03, OR 1.06 [1.00-1.11]) 1-year after hospital discharge were independently associated with persistence of symptoms.

Conclusions

Long COVID appears mainly related to respiratory sequelae, prevalently observed during the first pandemic wave. Among patients with little or no residual lung damage, a cytokine pattern consistent with systemic inflammation is in place.