Jasmin D Haslbauer, Spasenija Savic Prince, Anna K Stalder, Matthias S Matter, Carl P Zinner, Kathleen Jahn, Ellen Obermann, Jasmin Hanke, Karoline Leuzinger, Hans H Hirsch, Alexandar Tzankov
{"title":"SARS-CoV-2 阳性支气管肺泡灌洗液的不同基因表达:病例系列。","authors":"Jasmin D Haslbauer, Spasenija Savic Prince, Anna K Stalder, Matthias S Matter, Carl P Zinner, Kathleen Jahn, Ellen Obermann, Jasmin Hanke, Karoline Leuzinger, Hans H Hirsch, Alexandar Tzankov","doi":"10.1159/000532057","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce.</p><p><strong>Objectives: </strong>This case series seeks to characterize the intra-alveolar immunopathology of COVID-19.</p><p><strong>Method: </strong>BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n = 1), unremarkable BALs (n = 3), infections with respiratory syncytial virus (n = 1), influenza B (n = 1), and infections with other coronaviruses (n = 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while the detection of other pathogens was performed by immunofluorescence or multiplex NAT.</p><p><strong>Results: </strong>Gene expression profiling showed 71 significantly downregulated and 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated transcripts included genes involved in macrophage development, polarization, and crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), and genes involved in chemokine signaling and immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated transcripts featured genes involved in NK-T cell signaling (GZMA, GZMH, GNLY, PRF1, CD3G). Patients with mild COVID-19 showed a significant upregulation of genes involved in blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), and a zinc metalloprotease elevated in asthma (CPA3) compared to asymptomatic cases. In-silico comparison of the 5 COVID-19 BAL cases to a published cohort of lethal COVID-19 showed a significant upregulation of \"antigen processing and presentation\" and \"lysosome\" pathways in lethal cases.</p><p><strong>Conclusions: </strong>These data underscore the heterogeneity of immune response in COVID-19. Further studies with a larger dataset are required to gain a better understanding of the hallmarks of SARS-CoV-2 immunological response.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997241/pdf/","citationCount":"0","resultStr":"{\"title\":\"Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series.\",\"authors\":\"Jasmin D Haslbauer, Spasenija Savic Prince, Anna K Stalder, Matthias S Matter, Carl P Zinner, Kathleen Jahn, Ellen Obermann, Jasmin Hanke, Karoline Leuzinger, Hans H Hirsch, Alexandar Tzankov\",\"doi\":\"10.1159/000532057\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce.</p><p><strong>Objectives: </strong>This case series seeks to characterize the intra-alveolar immunopathology of COVID-19.</p><p><strong>Method: </strong>BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n = 1), unremarkable BALs (n = 3), infections with respiratory syncytial virus (n = 1), influenza B (n = 1), and infections with other coronaviruses (n = 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while the detection of other pathogens was performed by immunofluorescence or multiplex NAT.</p><p><strong>Results: </strong>Gene expression profiling showed 71 significantly downregulated and 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated transcripts included genes involved in macrophage development, polarization, and crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), and genes involved in chemokine signaling and immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated transcripts featured genes involved in NK-T cell signaling (GZMA, GZMH, GNLY, PRF1, CD3G). Patients with mild COVID-19 showed a significant upregulation of genes involved in blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), and a zinc metalloprotease elevated in asthma (CPA3) compared to asymptomatic cases. In-silico comparison of the 5 COVID-19 BAL cases to a published cohort of lethal COVID-19 showed a significant upregulation of \\\"antigen processing and presentation\\\" and \\\"lysosome\\\" pathways in lethal cases.</p><p><strong>Conclusions: </strong>These data underscore the heterogeneity of immune response in COVID-19. Further studies with a larger dataset are required to gain a better understanding of the hallmarks of SARS-CoV-2 immunological response.</p>\",\"PeriodicalId\":19805,\"journal\":{\"name\":\"Pathobiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997241/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pathobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000532057\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/7/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000532057","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series.
Background: Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce.
Objectives: This case series seeks to characterize the intra-alveolar immunopathology of COVID-19.
Method: BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n = 1), unremarkable BALs (n = 3), infections with respiratory syncytial virus (n = 1), influenza B (n = 1), and infections with other coronaviruses (n = 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while the detection of other pathogens was performed by immunofluorescence or multiplex NAT.
Results: Gene expression profiling showed 71 significantly downregulated and 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated transcripts included genes involved in macrophage development, polarization, and crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), and genes involved in chemokine signaling and immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated transcripts featured genes involved in NK-T cell signaling (GZMA, GZMH, GNLY, PRF1, CD3G). Patients with mild COVID-19 showed a significant upregulation of genes involved in blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), and a zinc metalloprotease elevated in asthma (CPA3) compared to asymptomatic cases. In-silico comparison of the 5 COVID-19 BAL cases to a published cohort of lethal COVID-19 showed a significant upregulation of "antigen processing and presentation" and "lysosome" pathways in lethal cases.
Conclusions: These data underscore the heterogeneity of immune response in COVID-19. Further studies with a larger dataset are required to gain a better understanding of the hallmarks of SARS-CoV-2 immunological response.
期刊介绍:
''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.