Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 19:13:1038227.
doi: 10.3389/fimmu.2022.1038227. eCollection 2022.

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

Mattia Bellan  1   2 , Daria Apostolo  1 , Alice Albè  1   2 , Martina Crevola  1   2 , Nicolò Errica  1   2 , Giacomo Ratano  1   2 , Stelvio Tonello  1 , Rosalba Minisini  1 , Davide D'Onghia  1 , Alessio Baricich  1   2 , Filippo Patrucco  1   2 , Patrizia Zeppegno  1   2 , Carla Gramaglia  1   2 , Piero Emilio Balbo  2 , Giuseppe Cappellano  1 , Sara Casella  1 , Annalisa Chiocchetti  1 , Elisa Clivati  2 , Mara Giordano  1   2 , Marcello Manfredi  1 , Giuseppe Patti  1   2 , David James Pinato  1   3 , Chiara Puricelli  1   2 , Davide Raineri  1 , Roberta Rolla  1 , Pier Paolo Sainaghi  1   2 , Mario Pirisi  1   2 ; No-More COVID study group
Collaborators, Affiliations

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

Mattia Bellan et al. Front Immunol. .

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.

Keywords: DLCO; SARS-CoV-2 infection; cytokines; depression; long COVID-19.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Mehandru S, Merad M. Pathological sequelae of long-haul COVID. Nat Immunol (2022) 23:194–202. doi: 10.1038/s41590-021-01104-y - DOI - PMC - PubMed
    1. Bellan M, Soddu D, Balbo PE, Baricich A, Zeppegno P, Avanzi GC, et al. Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge. JAMA Netw Open (2021) 4:e2036142. doi: 10.1001/jamanetworkopen.2020.36142 - DOI - PMC - PubMed
    1. Huang L, Li X, Gu X, Zhang H, Ren L, Guo L, et al. Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study. Lancet Respir Med (2022) 10(9):863–76. doi: 10.1016/S2213-2600(22)00126-6 - DOI - PMC - PubMed
    1. National Institute for Health and Care Excellence . COVID-19 rapid guideline: managing the long-term effects of COVID-19 NICE guideline (2020). Available at: https://www.nice.org.uk/guidance/ng188/chapter/Recommendations. - PubMed
    1. Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. BMJ (2021) 374:n1648. doi: 10.1136/bmj.n1648 - DOI - PubMed

Publication types