b'Genetic Changes Increase LikelihoodOf Poor COVID-19 OutcomesIn Chronic Lung DiseasesBecause they are molecularly susceptible to SARS-CoV-2, patients with chronic lung diseases appear to be primed for worse outcomes after infection. The authors cautioned that patients with idiopathic pulmonary fibrosis are most at risk, but the greater danger also affects those withchronic obstructive pulmonary disease and interstitial lung disease.By Mary Anne DunkinTEMPE,AZAirborneenvironmentalexposuresAsscientistsandphysicians,wewantedto during military service including Agent Orange,contribute to the urgent need to understand more burn pits, sandstorms or fumes from aircraft exhaustabout the COVID-19 pandemic and the virus that putveteransatanincreasedriskofchroniclungcaused it, SARS-CoV-2, said Linh T. Bui, PhD, conditionssuchaschronicobstructivepulmonaryapostdoctoralresearchfellowatTGenandlead disease (COPD), interstitial lung disease (ILD) andauthor of the study, which was published in Nature especially idiopathic pulmonary fibrosis (IPF). Communications. While we were not virologists, (High rates of use of tobacco products, which haveour labs have been studying the genetic composi-beendocumentedincurrentandformerservice- tion of ILD and have considerably deep knowledge members, just further exacerbate the diagnoses.)of the genetic and molecular mechanisms that regu-Theseconditions,whichhavegrowninpreva- late lung homeostasis and disease, and how these lence and incidence among veterans over the pastprograms changed in disease.decade, have presented a particular concern duringFor their work in ILD, the group had collected a the pandemic, as patients with chronic lung diseaselarge single-cell RNA sequencing (scRNA-seq) data (CLD) have been shown to have increased risk ofsetderivedfromtissuesthatcamefrompatients severe disease and significantly higher COVID-19with chronic lung disease and others with healthy mortality rate. lungs, said Bui. We quickly realized that we had the A recent study, which details the genetic changesunique opportunity to gain an understanding of why causedbychroniclungdiseaseinthemolecularpatients with chronic lung disease are doing poorly makeup of a variety of cells, including the epithelialwith SARS-CoV-2 infection and severity.cells that line the lung and airways, helps explainTo increase the scope and power of their study, the why chronic lung disease puts people at increasedresearchers pulled together a group of researchers for poor COVID-19 outcomes, and potentially offerswith similar datasets. The result of this collaboration new insight into reducing that risk.1 was an integrated scRNA-seq dataset consisting of The international study was led by researchers attranscriptomes of 611,398 single cells from healthy Translational Genomics Research Institute (TGen)(78 samples) and CLD lungs, including obstructive Tempe, AZ, who wanted to put the knowledge theypulmonary disease (COPD, 31 samples), idiopathic had gained on the genetics of one form of chronicpulmonary fibrosis (IPF, 82 samples) and other non-lung diseaseILD to improve the understandingIPF interstitial lung diseases (19 samples).of how COVID-19 affect people with that and otherSecond,theresearchersminedintothelitera-lung diseases.turetogainsomeunderstandingoftheknown Continued on Page 108 u106'