Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Eur Respir Rev ; 30(162)2021 Dec 31.
Article in English | MEDLINE | ID: covidwho-1575132


Acute manifestations of SARS-CoV-2 infection continue to impact the lives of many across the world. Post-acute sequelae of coronavirus disease 2019 (COVID-19) may affect 10-30% of survivors of COVID-19, and post-acute sequelae of COVID-19 (PASC)-pulmonary fibrosis is a long-term outcome associated with major morbidity. Data from prior coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome) suggest that pulmonary fibrosis will contribute to long-term respiratory morbidity, suggesting that PASC-pulmonary fibrosis should be thoroughly screened for through pulmonary function testing and cross-sectional imaging. As data accumulates on the unique pathobiologic mechanisms underlying critical COVID-19, a focus on corollaries to the subacute and chronic profibrotic phenotype must be sought as well. Key aspects of acute COVID-19 pathobiology that may account for increased rates of pulmonary fibrosis include monocyte/macrophage-T-cell circuits, profibrotic RNA transcriptomics, protracted elevated levels of inflammatory cytokines, and duration of illness and ventilation. Mechanistic understanding of PASC-pulmonary fibrosis will be central in determining therapeutic options and will ultimately play a role in transplant considerations. Well-designed cohort studies and prospective clinical registries are needed. Clinicians, researchers and healthcare systems must actively address this complication of PASC to minimise disability, maximise quality of life and confront a post-COVID-19 global health crisis.

COVID-19 , Pulmonary Fibrosis , Humans , Pandemics , Prospective Studies , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/epidemiology , Quality of Life , SARS-CoV-2
Am J Respir Cell Mol Biol ; 64(2): 158-160, 2021 02.
Article in English | MEDLINE | ID: covidwho-1263978
Sci Adv ; 6(33): eabb7238, 2020 08.
Article in English | MEDLINE | ID: covidwho-733188


Cigarette smoking, the leading cause of chronic obstructive pulmonary disease (COPD), has been implicated as a risk factor for severe disease in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we show that mice with lung epithelial cell-specific loss of function of Miz1, which we identified as a negative regulator of nuclear factor κB (NF-κB) signaling, spontaneously develop progressive age-related changes resembling COPD. Furthermore, loss of Miz1 up-regulates the expression of Ace2, the receptor for SARS-CoV-2. Concomitant partial loss of NF-κB/RelA prevented the development of COPD-like phenotype in Miz1-deficient mice. Miz1 protein levels are reduced in the lungs from patients with COPD, and in the lungs of mice exposed to chronic cigarette smoke. Our data suggest that Miz1 down-regulation-induced sustained activation of NF-κB-dependent inflammation in the lung epithelium is sufficient to induce progressive lung and airway destruction that recapitulates features of COPD, with implications for COVID-19.

Epithelial Cells/metabolism , Kruppel-Like Transcription Factors/metabolism , Lung/metabolism , Peptidyl-Dipeptidase A/metabolism , Phenotype , Protein Inhibitors of Activated STAT/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Ubiquitin-Protein Ligases/genetics , Up-Regulation/genetics , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Gene Knockout Techniques , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Protein Inhibitors of Activated STAT/metabolism , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/metabolism , SARS-CoV-2 , Signal Transduction/genetics , Smoking/adverse effects , Transcription Factor RelA/metabolism , Ubiquitin-Protein Ligases/metabolism