Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS
<h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19...
Ausführliche Beschreibung
Autor*in: |
Richa Batra [verfasserIn] William Whalen [verfasserIn] Sergio Alvarez-Mulett [verfasserIn] Luis G. Gomez-Escobar [verfasserIn] Katherine L. Hoffman [verfasserIn] Will Simmons [verfasserIn] John Harrington [verfasserIn] Kelsey Chetnik [verfasserIn] Mustafa Buyukozkan [verfasserIn] Elisa Benedetti [verfasserIn] Mary E. Choi [verfasserIn] Karsten Suhre [verfasserIn] Edward Schenck [verfasserIn] Augustine M. K. Choi [verfasserIn] Frank Schmidt [verfasserIn] Soo Jung Cho [verfasserIn] Jan Krumsiek [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Übergeordnetes Werk: |
In: PLoS Pathogens - Public Library of Science (PLoS), 2005, 18(2022), 9 |
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Übergeordnetes Werk: |
volume:18 ; year:2022 ; number:9 |
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DOAJ084384824 |
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520 | |a <h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. | ||
653 | 0 | |a Immunologic diseases. Allergy | |
653 | 0 | |a Biology (General) | |
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700 | 0 | |a Sergio Alvarez-Mulett |e verfasserin |4 aut | |
700 | 0 | |a Luis G. Gomez-Escobar |e verfasserin |4 aut | |
700 | 0 | |a Katherine L. Hoffman |e verfasserin |4 aut | |
700 | 0 | |a Will Simmons |e verfasserin |4 aut | |
700 | 0 | |a John Harrington |e verfasserin |4 aut | |
700 | 0 | |a Kelsey Chetnik |e verfasserin |4 aut | |
700 | 0 | |a Mustafa Buyukozkan |e verfasserin |4 aut | |
700 | 0 | |a Elisa Benedetti |e verfasserin |4 aut | |
700 | 0 | |a Mary E. Choi |e verfasserin |4 aut | |
700 | 0 | |a Karsten Suhre |e verfasserin |4 aut | |
700 | 0 | |a Edward Schenck |e verfasserin |4 aut | |
700 | 0 | |a Augustine M. K. Choi |e verfasserin |4 aut | |
700 | 0 | |a Frank Schmidt |e verfasserin |4 aut | |
700 | 0 | |a Soo Jung Cho |e verfasserin |4 aut | |
700 | 0 | |a Jan Krumsiek |e verfasserin |4 aut | |
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(DE-627)DOAJ084384824 (DE-599)DOAJ045db0b9a19544b4881ea62a59729541 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Richa Batra verfasserin aut Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. Immunologic diseases. Allergy Biology (General) William Whalen verfasserin aut Sergio Alvarez-Mulett verfasserin aut Luis G. Gomez-Escobar verfasserin aut Katherine L. Hoffman verfasserin aut Will Simmons verfasserin aut John Harrington verfasserin aut Kelsey Chetnik verfasserin aut Mustafa Buyukozkan verfasserin aut Elisa Benedetti verfasserin aut Mary E. Choi verfasserin aut Karsten Suhre verfasserin aut Edward Schenck verfasserin aut Augustine M. K. Choi verfasserin aut Frank Schmidt verfasserin aut Soo Jung Cho verfasserin aut Jan Krumsiek verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 18(2022), 9 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:18 year:2022 number:9 https://doaj.org/article/045db0b9a19544b4881ea62a59729541 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484674/?tool=EBI kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2022 9 |
spelling |
(DE-627)DOAJ084384824 (DE-599)DOAJ045db0b9a19544b4881ea62a59729541 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Richa Batra verfasserin aut Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. Immunologic diseases. Allergy Biology (General) William Whalen verfasserin aut Sergio Alvarez-Mulett verfasserin aut Luis G. Gomez-Escobar verfasserin aut Katherine L. Hoffman verfasserin aut Will Simmons verfasserin aut John Harrington verfasserin aut Kelsey Chetnik verfasserin aut Mustafa Buyukozkan verfasserin aut Elisa Benedetti verfasserin aut Mary E. Choi verfasserin aut Karsten Suhre verfasserin aut Edward Schenck verfasserin aut Augustine M. K. Choi verfasserin aut Frank Schmidt verfasserin aut Soo Jung Cho verfasserin aut Jan Krumsiek verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 18(2022), 9 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:18 year:2022 number:9 https://doaj.org/article/045db0b9a19544b4881ea62a59729541 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484674/?tool=EBI kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2022 9 |
allfields_unstemmed |
(DE-627)DOAJ084384824 (DE-599)DOAJ045db0b9a19544b4881ea62a59729541 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Richa Batra verfasserin aut Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. Immunologic diseases. Allergy Biology (General) William Whalen verfasserin aut Sergio Alvarez-Mulett verfasserin aut Luis G. Gomez-Escobar verfasserin aut Katherine L. Hoffman verfasserin aut Will Simmons verfasserin aut John Harrington verfasserin aut Kelsey Chetnik verfasserin aut Mustafa Buyukozkan verfasserin aut Elisa Benedetti verfasserin aut Mary E. Choi verfasserin aut Karsten Suhre verfasserin aut Edward Schenck verfasserin aut Augustine M. K. Choi verfasserin aut Frank Schmidt verfasserin aut Soo Jung Cho verfasserin aut Jan Krumsiek verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 18(2022), 9 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:18 year:2022 number:9 https://doaj.org/article/045db0b9a19544b4881ea62a59729541 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484674/?tool=EBI kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2022 9 |
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(DE-627)DOAJ084384824 (DE-599)DOAJ045db0b9a19544b4881ea62a59729541 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Richa Batra verfasserin aut Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. Immunologic diseases. Allergy Biology (General) William Whalen verfasserin aut Sergio Alvarez-Mulett verfasserin aut Luis G. Gomez-Escobar verfasserin aut Katherine L. Hoffman verfasserin aut Will Simmons verfasserin aut John Harrington verfasserin aut Kelsey Chetnik verfasserin aut Mustafa Buyukozkan verfasserin aut Elisa Benedetti verfasserin aut Mary E. Choi verfasserin aut Karsten Suhre verfasserin aut Edward Schenck verfasserin aut Augustine M. K. Choi verfasserin aut Frank Schmidt verfasserin aut Soo Jung Cho verfasserin aut Jan Krumsiek verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 18(2022), 9 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:18 year:2022 number:9 https://doaj.org/article/045db0b9a19544b4881ea62a59729541 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484674/?tool=EBI kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2022 9 |
allfieldsSound |
(DE-627)DOAJ084384824 (DE-599)DOAJ045db0b9a19544b4881ea62a59729541 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Richa Batra verfasserin aut Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. Immunologic diseases. Allergy Biology (General) William Whalen verfasserin aut Sergio Alvarez-Mulett verfasserin aut Luis G. Gomez-Escobar verfasserin aut Katherine L. Hoffman verfasserin aut Will Simmons verfasserin aut John Harrington verfasserin aut Kelsey Chetnik verfasserin aut Mustafa Buyukozkan verfasserin aut Elisa Benedetti verfasserin aut Mary E. Choi verfasserin aut Karsten Suhre verfasserin aut Edward Schenck verfasserin aut Augustine M. K. Choi verfasserin aut Frank Schmidt verfasserin aut Soo Jung Cho verfasserin aut Jan Krumsiek verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 18(2022), 9 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:18 year:2022 number:9 https://doaj.org/article/045db0b9a19544b4881ea62a59729541 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484674/?tool=EBI kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2022 9 |
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Richa Batra @@aut@@ William Whalen @@aut@@ Sergio Alvarez-Mulett @@aut@@ Luis G. Gomez-Escobar @@aut@@ Katherine L. Hoffman @@aut@@ Will Simmons @@aut@@ John Harrington @@aut@@ Kelsey Chetnik @@aut@@ Mustafa Buyukozkan @@aut@@ Elisa Benedetti @@aut@@ Mary E. Choi @@aut@@ Karsten Suhre @@aut@@ Edward Schenck @@aut@@ Augustine M. K. Choi @@aut@@ Frank Schmidt @@aut@@ Soo Jung Cho @@aut@@ Jan Krumsiek @@aut@@ |
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Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS |
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Richa Batra William Whalen Sergio Alvarez-Mulett Luis G. Gomez-Escobar Katherine L. Hoffman Will Simmons John Harrington Kelsey Chetnik Mustafa Buyukozkan Elisa Benedetti Mary E. Choi Karsten Suhre Edward Schenck Augustine M. K. Choi Frank Schmidt Soo Jung Cho Jan Krumsiek |
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multi-omic comparative analysis of covid-19 and bacterial sepsis-induced ards |
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Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS |
abstract |
<h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. |
abstractGer |
<h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. |
abstract_unstemmed |
<h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation. |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ084384824</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230501173458.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230311s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ084384824</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ045db0b9a19544b4881ea62a59729541</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH301-705.5</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Richa Batra</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a"><h4<Background</h4< Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. <h4<Methods and findings</h4< In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. <h4<Conclusion</h4< We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. Allergy</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">William Whalen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sergio Alvarez-Mulett</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luis G. Gomez-Escobar</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Katherine L. 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