Post-viral parenchymal lung disease following COVID-19 and viral pneumonitis hospitalisation: A systematic review and meta-analysis

Background Approximately half of COVID-19 survivors present persisting breathlessness, which may include development of pulmonary fibrosis. Research Question What is the prevalence of long-term radiological and functional pulmonary sequelae of parenchymal lung disease following hospitalisation with COVID-19 and other viral pneumonia? Study design and methods We performed systematic review and random effects meta-analysis of studies in adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV, or Influenza pneumonia and followed within 12 months from discharge. Searches were run on MEDLINE and Embase, updated 29 July 2021. Primary outcomes were proportion of 1) radiologic sequelae at CT scans; 2) restrictive impairment; 3) impaired gas transfer. Heterogeneity was explored in meta-regression. Results Ninety-five studies were included for qualitative synthesis, of which 70 were suitable for meta-analysis, including 60 studies of SARS-CoV-2 with a median follow up of 3 months. In SARS-CoV-2 the overall estimated proportion of inflammatory changes during follow up was 0.50 (95%CI 0.41 to 0.58, I2=94.6%), whilst fibrotic changes were estimated at 0.29 (95%CI 0.22 to 0.37, I2=94.1%). Inflammatory changes reduced compared with CTs performed during hospitalisation (−0.47; 95%CI -0.56 to -0.37), whereas no significant resolution was observed in fibrotic changes (−0.09; 95%CI -0.25 to 0.07). Impaired gas transfer was estimated at 0.38 (95%CI 0.32 to 0.44, I2=92.1%), which was greater than estimated restrictive impairment (0.17; 95%CI 0.13 to 0.23, I2=92.5%). High heterogeneity means that estimates should be interpreted with caution. Confidence in the estimates was deemed low due to the heterogeneity and because studies were largely observational without controls. Interpretation A substantial proportion of radiological and functional sequelae consistent with parenchymal lung disease are observed following COVID-19 and other viral pneumonitis. Estimates of prevalence are limited by differences in case mix and initial severity. This highlights the importance of extended radiological and functional follow-up post hospitalisation. PROSPERO registration CRD42020183139 (April 2020) ### Competing Interest Statement LF, SM, FK, WC, JX, KR, AS and IS report no competing interests relating to the manuscript, GJ reports NIHR BRC salaries, studentships, professorship (RP-2017-08-ST2-014). GJ also reports consulting fees and honoraria from Biogen, Galapagos, Galecto, GlaxoSmithKline, Heptares, MedImmuine, Pliant, PharmAkea, Bristol Myers Squibb, Veracyte, Boehringer Ingelheim, NordicBiosciences, Roche, Chiesi. ### Clinical Protocols ### Funding Statement Funding was supported by National Institute for Health Research (NIHR), the funders had no involvement in any aspect of the submitted work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: University of Nottingham Ethics Committee All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data are publicly available in published manuscripts, and can be shared upon reasonable request * CT : computed tomography DLCO : diffusing capacity for carbon monoxide FEV1 : forced expiratory volume in the first second FVC : forced vital capacity TLC : total lung capacity