b'u From Page 106pathways involved in SARS-CoV-2 viral entry, infection and host responses. We then focused our study on the expression ofgenesinthesepathwaysindisease lungsversushealthycontrollungsand whetherchangesingeneexpressionled to the alterations of these pathways that result in a more severe response to SARS-CoV-2 infection, Bui said.In the cells of CLD patients the research-ers observed broad changes and dysregula-tion in the gene expression profile related to viral infection and host response, sug-gestingthatCLDpatientsmayrespond completelydifferentlytoviralinfection, including SARS-CoV2, compared to indi-viduals without lung disease.Specifically, they identified in patients with CLD a preexisting dysregulation of genesAn air crew walks in from the flight line during a sandstorm at Sather Air Base, Iraq, in involved in viral infection and the immune2006. Exposures such as that increase risk of chronic lung diseases, which, in turn, can response in the disease epithelial cells, espe- make COVID-19 more severe. U.S. Air Force photo by Staff Sgt. William Bennettcially AT2 cells, compared to healthy cells.Asevereinflammatoryconditioncalledacutefor worse outcomes after infection, through the dys-respiratory distress syndrome, or ARDs, can be trig- regulation of genes related to viral replication and gered in a viral infection, said Bui. In ARDS, dam- the innate immune response in epithelial cells, and age to alveolar cellsboth AT2 and Type 1 (AT1) basal differences in inflammatory cell gene expres-will lead to the alveolus being filled with fluid andsion programs, Bui said.inflammatory cells; thus, preventing gas exchange,The findings have the potential to affect decisions shesaid.ManyofthepatientswithCOVID-19concerning the treatment plan and medication being who were hospitalized in an ICU or died developedadministered to patients when they are hospitalized ARDS in response to their infection. due to COVID-19 infection, said Bui. For example, Otherkeyfindingsofthestudyincludedtheserum interleukin-6 elevation was previously found following:to associate with COVID-19 severity and mortality,The viral entry score, which is a composite of alland the use of tocilizumab, an IL-6 antibody, has genes associated with SARS-CoV-2 entry intobeen used in COVID-19 treatment to treat COVID-the cells, is increased in the lungs of patients19 induced cytokine storm, she said. In our study, with CLD. we found that IL-6 associated tocilizumab respon- Patients with CLD have a higher proportion ofsive genes are expressed higher in the IPF and other-CD4, CD8 and NK cells than controls. ILD samples, but not COPD samples; thus, suggest- The expression of cytotoxicity and exhaustioning that different COVID-19 treatment approaches genes in the T-cell populations is increased andshouldbeconsideredwhenitcomestopatients there are alterations in the expression level ofcomorbidities. genes involved in the viral response pathways1Bui LT, Winters NI, Chung MI, Joseph C, Gutierrez AJ, et. al. Human Cell Atlas Lung Biological Network. Chronic lung diseases are associ-(interferon, antigen presentation) in diseaseated with gene expression programs favoring SARS-CoV-2 entry and compared to healthy cells. severity. Nat Commun. 2021 Jul 14;12(1):4314. doi: 10.1038/s41467-In short, patients with chronic lung disease may be021-24467-0. PMID: 34262047; PMCID: PMC8280215.molecularly susceptible to SARS-CoV-2 and primed 108'