Frontiers in Immunology (Dec 2022)

Determinants of long COVID among adults hospitalized for SARS-CoV-2 infection: A prospective cohort study

  • Mattia Bellan,
  • Mattia Bellan,
  • Daria Apostolo,
  • Alice Albè,
  • Alice Albè,
  • Martina Crevola,
  • Martina Crevola,
  • Nicolò Errica,
  • Nicolò Errica,
  • Giacomo Ratano,
  • Giacomo Ratano,
  • Stelvio Tonello,
  • Rosalba Minisini,
  • Davide D’Onghia,
  • Alessio Baricich,
  • Alessio Baricich,
  • Filippo Patrucco,
  • Filippo Patrucco,
  • Patrizia Zeppegno,
  • Patrizia Zeppegno,
  • Carla Gramaglia,
  • Carla Gramaglia,
  • Piero Emilio Balbo,
  • Giuseppe Cappellano,
  • Sara Casella,
  • Annalisa Chiocchetti,
  • Elisa Clivati,
  • Mara Giordano,
  • Mara Giordano,
  • Marcello Manfredi,
  • Giuseppe Patti,
  • Giuseppe Patti,
  • David James Pinato,
  • David James Pinato,
  • Chiara Puricelli,
  • Chiara Puricelli,
  • Davide Raineri,
  • Roberta Rolla,
  • Pier Paolo Sainaghi,
  • Pier Paolo Sainaghi,
  • Mario Pirisi,
  • Mario Pirisi,
  • the No-More COVID study group,
  • Mattia Bellan,
  • Daria Apostolo,
  • Alice Albè,
  • Martina Crevola,
  • Errica Nicolò,
  • Giacomo Ratano,
  • Antonio Acquavivas,
  • Luigi Mario Castello,
  • Stelvio Tonello,
  • Rosalba Minisini,
  • Davide D’Onghia,
  • Alessio Baricich,
  • Filippo Patrucco,
  • Patrizia Zeppegno,
  • Carla Gramaglia,
  • Gian Carlo Avanzi,
  • Piero Emilio Balbo,
  • Giulia Baldon,
  • Michela Barini,
  • Marco Battaglia,
  • Simone Bor,
  • Vincenzo Cantaluppi,
  • Giuseppe Cappellano,
  • Alessandro Carriero,
  • Sara Casella,
  • Annalisa Chiocchetti,
  • Daria Cuneo,
  • Eleonora Gambaro,
  • Mara Giordano,
  • Luisa Isabella,
  • Alberto Loro,
  • Debora Marangon,
  • Emanuele Mones,
  • Elena Paracchini,
  • Giuseppe Patti,
  • David James Pinato,
  • Chiara Puricelli,
  • Davide Raineri,
  • Roberta Rolla,
  • Pier Paolo Sainaghi,
  • Stefano Tricca,
  • Mario Pirisi

DOI
https://doi.org/10.3389/fimmu.2022.1038227
Journal volume & issue
Vol. 13

Abstract

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RationaleFactors 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.MethodsA 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.ResultsIn 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.ConclusionsLong 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.

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