Genetic overlap between idiopathic pulmonary fibrosis and COVID-19

Genome-wide association studies (GWAS) of coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) have identified genetic loci associated with both traits, suggesting possible shared biological mechanisms. Using updated GWAS of COVID-19 and IPF, we evaluated the genetic overlap between these two diseases and identified four genetic loci (including one novel) with likely shared causal variants between severe COVID-19 and IPF. Although there was a positive genetic correlation between COVID-19 and IPF, two of these four shared genetic loci had an opposite direction of effect. IPF-associated genetic variants related to telomere dysfunction and spindle assembly showed no association with COVID-19 phenotypes. Together, these results suggest there are both shared and distinct biological processes driving IPF and severe COVID-19 phenotypes.

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

BackgroundApproximately half of COVID-19 survivors present persisting breathlessness, which may include development of pulmonary fibrosis. Research QuestionWhat 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 methodsWe 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. ResultsNinety-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. InterpretationA 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 registrationCRD42020183139 (April 2020)

A systematic review of Anakinra, Tocilizumab, Sarilumab and Siltuximab for coronavirus-related infections

BackgroundThere is accumulating evidence for an overly activated immune response in severe Covid-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of Covid-19. MethodsElectronic databases were searched on 7th January 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of Covid-19. The primary outcomes were severity on an ordinal scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality. Results71 studies totalling 22,058 patients were included, six were randomised trials. Most explored outcomes in patients who received tocilizumab (59/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (RR 0.83 95%CI 0.72;0.96 I2 = 0.0%), but conclusive benefit was not demonstrated for other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an ordinal scale (Generalised odds ratio 1.34 95%CI 1.10;1.64, I2=98%) and adjusted mortality risk (HR 0.52 95%CI 0.41;0.66, I2 =76.6%). The mean difference in duration of hospitalisation was 0.36 days (95%CI -0.07;0.80, I2 =93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent. ConclusionTocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in Covid-19 is insufficient, with further studies urgently needed for conclusive findings.