Six-month pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study

  1. Paola Faverio
  2. Fabrizio Luppi
  3. Paola Rebora
  4. Sara Busnelli
  5. Anna Stainer
  6. Martina Catalano
  7. Luca Parachini
  8. Anna Monzani
  9. Stefania Galimberti
  10. Francesco Bini
  11. Bruno Dino Bodini
  12. Monia Betti
  13. Federica De Giacomi
  14. Paolo Scarpazza
  15. Elisa Oggionni
  16. Alessandro Scartabellati
  17. Luca Bilucaglia
  18. Paolo Ceruti
  19. Denise Modina
  20. Sergio Harari
  21. Antonella Caminati
  22. Maria Grazia Valsecchi
  23. Giacomo Bellani
  24. Giuseppe Foti
  25. Alberto Pesci

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Abstract

Background and objective

Long-term pulmonary sequelae following SARS-CoV-2 pneumonia are not yet confirmed, however preliminary observations suggests a possible relevant clinical, functional and radiological impairment. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up.

Methods

In this multicenter, prospective, observational cohort study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (“oxygen only”, “continuous positive airway pressure (CPAP)” and “invasive mechanical ventilation (IMV)”) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 minutes walking test, chest X-ray, physical exam and modified Medical Research Council (mMRC) dyspnoea score were collected.

Results

Between March and June 2020, 312 patients were enrolled (83, 27% women; median [IQR] age 61.1 [53.4,69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest-X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥ 1, or showed a restrictive ventilatory defects (9%). In the logistic regression model, having asthma as comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalisation appeared as a protective factor. Need for invasive ventilatory support during hospitalisation was associated with chest imaging abnormalities.

Conclusion

DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

Summary at a glance

DLCO and radiological assessment are the most sensitive tools to monitor COVID-19 patients at 6-month follow-up. Invasive ventilatory support is a risk factor for detection of radiological abnormalities, but not for DLCO impairment, at follow-up. Whileuse of prophylactic heparin acts as a protective factor on the development of DLCOimpairment.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.29.21254151: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: CPAP and IMV were applied according to the position papers on the management of respiratory failure in patients with COVID-19.11 This study received Ethics Committee approval (ASST Monza, 3389, May 21st 2020) and was registered on clinicaltrial.gov (ClinicalTrials.gov Identifier: NCT04435327).
    Consent: All patients provided written informed consent at the time of enrolment.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisStatistical analysis: A sample size of 360 patients was calculated to provide 80% power to detect an increase from 2% (patients who received oxygen therapy alone) to 10% (patients who received CPAP or IMV) in the percentage of pulmonary sequelae at 1 year after hospital discharge with a logistic regression model and a statistical significance of 0.05.
    Sex as a biological variable16 The lower limits of normal for distance walked in healthy men and women were calculated according to the equation created by Enright and colleagues.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study presents also some limitations: 1) the study visits were conducted during the second pandemic wave and this may have contributed to the lost to follow-up of some patients that were afraid of going to the hospital for medical visits, however the distribution of age and gender was similar among all patients recruited and patients actually visited; 2) data on the severity of radiological involvement during hospitalization, that may have had an impact on the development of pulmonary sequelae, were not collected, although the maximum ventilatory support needed by the patients gave us an hint about the severity of pneumonia. In conclusion, up to 58% of patients with COVID-19, according to study group, present pulmonary sequelae, although of mild entity in the majority of cases, at 6-month follow-up. DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 during follow-up. Need for invasive ventilatory support during hospitalization is a risk factor for detection of radiological abnormalities, but not for DLCO impairment, at follow-up. While use of prophylactic heparin acts as a protective factor on the development of DLCO impairment. Future studies should evaluate the pulmonary sequelae developed by patients in the second and subsequent pandemic waves to assess the impact of standard-of-care therapies, such as steroid and heparin, that were not routinely used during the first wave. Furthermore, we await data on long-term se...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04435327RecruitingLung Damage Caused by SARS-CoV-2 Pneumonia (COVID-19)

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  2. Version published to 10.1101/2021.03.29.21254151v1 on medRxiv
  3. Version published to 10.1159/000518141