Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis

  1. Laura Fabbri
  2. Samuel Moss
  3. Fasihul A Khan
  4. Wenjie Chi
  5. Jun Xia
  6. Karen Robinson
  7. Alan Robert Smyth
  8. Gisli Jenkins
  9. Iain Stewart

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Abstract

Persisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up of people hospitalised with COVID-19 and viral pneumonitis.

Methods

Systematic review and random effects meta-analysis of proportions using studies of adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV or influenza pneumonia and followed up within 12 months. Searches performed in MEDLINE and Embase. Primary outcomes were proportion of radiological sequelae on CT scans; restrictive impairment; impaired gas transfer. Heterogeneity was explored in meta-regression.

Results

Ninety-five studies (98.9% observational) were included in qualitative synthesis, 70 were suitable for meta-analysis including 60 SARS-CoV-2 studies with a median follow-up of 3 months. In SARS-CoV-2, the overall estimated proportion of inflammatory sequelae was 50% during follow-up (0.50; 95% CI 0.41 to 0.58; I 2 =95%), fibrotic sequelae were estimated in 29% (0.29; 95% CI 0.22 to 0.37; I 2 =94.1%). Follow-up time was significantly associated with estimates of inflammatory sequelae (−0.036; 95% CI −0.068 to –0.004; p=0.029), associations with fibrotic sequelae did not reach significance (−0.021; 95% CI −0.051 to 0.009; p=0.176). Impaired gas transfer was estimated at 38% of lung function tests (0.38 95% CI 0.32 to 0.44; I 2 =92.1%), which was greater than restrictive impairment (0.17; 95% CI 0.13 to 0.23; I 2 =92.5%), neither were associated with follow-up time (p=0.207; p=0.864).

Discussion

Sequelae consistent with parenchymal lung disease were observed following COVID-19 and other viral pneumonitis. Estimates should be interpreted with caution due to high heterogeneity, differences in study casemix and initial severity.

PROSPERO registration number

CRD42020183139.

Article activity feed

  1. Version published to 10.1136/thoraxjnl-2021-218275
  2. ScreenIT

    SciScore for 10.1101/2021.03.15.21253593: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Studies were identified by searching MEDLINE (1946 to latest), Embase (1974 to latest), and Google Scholar.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    (TX: StataCorp LLC) using the metaprop command, which computes 95% confidence intervals based on binomial distribution and applies the Freeman-Tukey double arcsine transformation to support inclusion of observations of 0% and 100%.
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    There are a number of limitations associated with this review. As our search strategy focused on follow-up, the number of included articles that reported baseline findings was limited, particularly regarding SARS-CoV infection, whilst contemporary SARS-CoV-2 papers had limited follow-up length. Furthermore, estimates of proportion are based on the number of tests performed, and not patients infected, which could be affected by selection bias. Similarly, estimates represent people hospitalised with infection, which may not reflect prevalence in non-hospitalised cases. Caution is required in interpreting overall and summary estimates as heterogeneity in estimated proportions was frequently considerable, which was not completely attributable to the study-level features evaluated. It is likely that variability in case mix and severity within studies contributes to the heterogeneity between them, which may be addressed by individual patient data approaches. We defined radiological sequelae extracted from studies regarded to be attributable to inflammatory and fibrotic responses, however these were not always reported specifically or exclusively, and there are limitations of our predefined radiological outcomes. Ground-glass opacities do not necessarily reflect inflammation and could also reflect retractile fibrosis during follow up. Unfortunately, it is not possible to discriminate between the two without histopathology. Internationally standardised approaches to reporting of post...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.03.15.21253593 on medRxiv