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Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19
Institution:1. Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;2. Division of General Internal Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;3. Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;4. Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;5. Division of Respiratory and Infectious Diseases, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;6. Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan;7. Department of Infectious Diseases, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;8. Department of Microbiology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan;9. Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan
Abstract:BackgroundThe role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated.MethodsWe conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19.ResultsIn this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively).ConclusionHigher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.
Keywords:COVID-19  Pyroptosis  Apoptosis  Gasdermin D  Caspase-cleaved cytokeratin 18 fragment  COVID-19"}  {"#name":"keyword"  "$":{"id":"kwrd0040"}  "$$":[{"#name":"text"  "_":"coronavirus disease 2019  ELISA"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"enzyme-linked immunosorbent assay  GSDMD"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"gasdermin D  GGO"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"ground glass opacity  ICU"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"intensive care unit  IFN"}  {"#name":"keyword"  "$":{"id":"kwrd0090"}  "$$":[{"#name":"text"  "_":"interferon  IL"}  {"#name":"keyword"  "$":{"id":"kwrd0100"}  "$$":[{"#name":"text"  "_":"interleukin  LDH"}  {"#name":"keyword"  "$":{"id":"kwrd0110"}  "$$":[{"#name":"text"  "_":"lactate dehydrogenase  MV"}  {"#name":"keyword"  "$":{"id":"kwrd0120"}  "$$":[{"#name":"text"  "_":"mechanical ventilation  M30"}  {"#name":"keyword"  "$":{"id":"kwrd0130"}  "$$":[{"#name":"text"  "_":"caspase-cleaved cytokeratin 18 fragment  SARS-CoV-2"}  {"#name":"keyword"  "$":{"id":"kwrd0140"}  "$$":[{"#name":"text"  "_":"severe acute respiratory syndrome coronavirus 2  TGF"}  {"#name":"keyword"  "$":{"id":"kwrd0150"}  "$$":[{"#name":"text"  "_":"transforming growth factor  TNF"}  {"#name":"keyword"  "$":{"id":"kwrd0160"}  "$$":[{"#name":"text"  "_":"tumor necrosis factor
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