Emerging pharmacological therapies for ARDS: COVID-19 and beyond.
Identifieur interne : 001046 ( Main/Exploration ); précédent : 001045; suivant : 001047Emerging pharmacological therapies for ARDS: COVID-19 and beyond.
Auteurs : Shahd Horie [Irlande (pays)] ; Bairbre Mcnicholas [Irlande (pays)] ; Emanuele Rezoagli [Irlande (pays), Italie] ; Tài Pham [France] ; Ger Curley [Irlande (pays)] ; Danny Mcauley [Royaume-Uni] ; Cecilia O'Kane [Royaume-Uni] ; Alistair Nichol [Irlande (pays), Australie] ; Claudia Dos Santos [Canada] ; Patricia R M. Rocco [Brésil] ; Giacomo Bellani [Italie] ; John G. Laffey [Irlande (pays)]Source :
- Intensive care medicine [ 1432-1238 ] ; 2020.
Abstract
ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.
DOI: 10.1007/s00134-020-06141-z
PubMed: 32654006
PubMed Central: PMC7352097
Affiliations:
- Australie, Brésil, Canada, France, Irlande (pays), Italie, Royaume-Uni
- Ontario, Victoria (État), État de Rio de Janeiro
- Melbourne, Rio de Janeiro, Toronto
- Université de Toronto
Links toward previous steps (curation, corpus...)
Le document en format XML
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wicri:level="1"><nlm:affiliation>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation></author><author><name sortKey="Rezoagli, Emanuele" sort="Rezoagli, Emanuele" uniqKey="Rezoagli E" first="Emanuele" last="Rezoagli">Emanuele Rezoagli</name><affiliation wicri:level="1"><nlm:affiliation>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medicine and Surgery, University of Milano - Bicocca, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Pham, Tai" sort="Pham, Tai" uniqKey="Pham T" first="Tài" last="Pham">Tài Pham</name><affiliation wicri:level="1"><nlm:affiliation>Service de médecine Intensive-Réanimation, AP-HP, 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sort="Mcauley, Danny" uniqKey="Mcauley D" first="Danny" last="Mcauley">Danny Mcauley</name><affiliation wicri:level="1"><nlm:affiliation>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland</wicri:regionArea><wicri:noRegion>Northern Ireland</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Intensive Care Medicine, Royal Victoria Hospital, Belfast, Northern Ireland, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Intensive Care Medicine, Royal Victoria Hospital, Belfast, Northern Ireland</wicri:regionArea><wicri:noRegion>Northern Ireland</wicri:noRegion></affiliation></author><author><name sortKey="O Kane, Cecilia" sort="O Kane, Cecilia" uniqKey="O Kane C" first="Cecilia" last="O'Kane">Cecilia O'Kane</name><affiliation wicri:level="1"><nlm:affiliation>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland</wicri:regionArea><wicri:noRegion>Northern Ireland</wicri:noRegion></affiliation></author><author><name sortKey="Nichol, Alistair" sort="Nichol, Alistair" uniqKey="Nichol A" first="Alistair" last="Nichol">Alistair Nichol</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Research Centre at St Vincent's University Hospital, University College Dublin, Dublin, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Clinical Research Centre at St Vincent's University Hospital, University College Dublin, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:affiliation>Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Intensive Care Unit, Alfred Hospital, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Intensive Care Unit, Alfred Hospital, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Dos Santos, Claudia" sort="Dos Santos, Claudia" uniqKey="Dos Santos C" first="Claudia" last="Dos Santos">Claudia Dos Santos</name><affiliation wicri:level="4"><nlm:affiliation>Keenan Research Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Keenan Research Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Rocco, Patricia R M" sort="Rocco, Patricia R M" uniqKey="Rocco P" first="Patricia R M" last="Rocco">Patricia R M. Rocco</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro</wicri:regionArea><placeName><settlement type="city">Rio de Janeiro</settlement><region type="state">État de Rio de Janeiro</region></placeName></affiliation></author><author><name sortKey="Bellani, Giacomo" sort="Bellani, Giacomo" uniqKey="Bellani G" first="Giacomo" last="Bellani">Giacomo Bellani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medicine and Surgery, University of Milano - Bicocca, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Laffey, John G" sort="Laffey, John G" uniqKey="Laffey J" first="John G" last="Laffey">John G. 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Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation></author><author><name sortKey="Mcnicholas, Bairbre" sort="Mcnicholas, Bairbre" uniqKey="Mcnicholas B" first="Bairbre" last="Mcnicholas">Bairbre Mcnicholas</name><affiliation wicri:level="1"><nlm:affiliation>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation></author><author><name sortKey="Rezoagli, Emanuele" sort="Rezoagli, Emanuele" uniqKey="Rezoagli E" first="Emanuele" last="Rezoagli">Emanuele Rezoagli</name><affiliation wicri:level="1"><nlm:affiliation>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medicine and Surgery, University of Milano - Bicocca, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Pham, Tai" sort="Pham, Tai" uniqKey="Pham T" first="Tài" last="Pham">Tài Pham</name><affiliation wicri:level="1"><nlm:affiliation>Service de médecine Intensive-Réanimation, AP-HP, Hôpital de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Le Kremlin-Bicêtre, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de médecine Intensive-Réanimation, AP-HP, Hôpital de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Le Kremlin-Bicêtre</wicri:regionArea><wicri:noRegion>Le Kremlin-Bicêtre</wicri:noRegion><wicri:noRegion>Le Kremlin-Bicêtre</wicri:noRegion></affiliation></author><author><name sortKey="Curley, Ger" sort="Curley, Ger" uniqKey="Curley G" first="Ger" last="Curley">Ger Curley</name><affiliation wicri:level="1"><nlm:affiliation>Department of Anaesthesiology, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Department of Anaesthesiology, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Mcauley, Danny" sort="Mcauley, Danny" uniqKey="Mcauley D" first="Danny" last="Mcauley">Danny Mcauley</name><affiliation wicri:level="1"><nlm:affiliation>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland</wicri:regionArea><wicri:noRegion>Northern Ireland</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Intensive Care Medicine, Royal Victoria Hospital, Belfast, Northern Ireland, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Intensive Care Medicine, Royal Victoria Hospital, Belfast, Northern Ireland</wicri:regionArea><wicri:noRegion>Northern Ireland</wicri:noRegion></affiliation></author><author><name sortKey="O Kane, Cecilia" sort="O Kane, Cecilia" uniqKey="O Kane C" first="Cecilia" last="O'Kane">Cecilia O'Kane</name><affiliation wicri:level="1"><nlm:affiliation>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland</wicri:regionArea><wicri:noRegion>Northern Ireland</wicri:noRegion></affiliation></author><author><name sortKey="Nichol, Alistair" sort="Nichol, Alistair" uniqKey="Nichol A" first="Alistair" last="Nichol">Alistair Nichol</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Research Centre at St Vincent's University Hospital, University College Dublin, Dublin, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Clinical Research Centre at St Vincent's University Hospital, University College Dublin, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:affiliation>Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Intensive Care Unit, Alfred Hospital, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Intensive Care Unit, Alfred Hospital, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Dos Santos, Claudia" sort="Dos Santos, Claudia" uniqKey="Dos Santos C" first="Claudia" last="Dos Santos">Claudia Dos Santos</name><affiliation wicri:level="4"><nlm:affiliation>Keenan Research Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Keenan Research Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Rocco, Patricia R M" sort="Rocco, Patricia R M" uniqKey="Rocco P" first="Patricia R M" last="Rocco">Patricia R M. Rocco</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro</wicri:regionArea><placeName><settlement type="city">Rio de Janeiro</settlement><region type="state">État de Rio de Janeiro</region></placeName></affiliation></author><author><name sortKey="Bellani, Giacomo" sort="Bellani, Giacomo" uniqKey="Bellani G" first="Giacomo" last="Bellani">Giacomo Bellani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medicine and Surgery, University of Milano - Bicocca, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Laffey, John G" sort="Laffey, John G" uniqKey="Laffey J" first="John G" last="Laffey">John G. Laffey</name><affiliation wicri:level="1"><nlm:affiliation>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway, Ireland. john.laffey@nuigalway.ie.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway, Ireland. john.laffey@nuigalway.ie.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway</wicri:regionArea><wicri:noRegion>Galway</wicri:noRegion></affiliation></author></analytic><series><title level="j">Intensive care medicine</title><idno type="eISSN">1432-1238</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32654006</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1432-1238</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Jul</Month><Day>11</Day></PubDate></JournalIssue><Title>Intensive care medicine</Title><ISOAbbreviation>Intensive Care Med</ISOAbbreviation></Journal><ArticleTitle>Emerging pharmacological therapies for ARDS: COVID-19 and beyond.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00134-020-06141-z</ELocationID><Abstract><AbstractText>ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Horie</LastName><ForeName>Shahd</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McNicholas</LastName><ForeName>Bairbre</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rezoagli</LastName><ForeName>Emanuele</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway, Ireland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pham</LastName><ForeName>Tài</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Service de médecine Intensive-Réanimation, AP-HP, Hôpital de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Le Kremlin-Bicêtre, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Curley</LastName><ForeName>Ger</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McAuley</LastName><ForeName>Danny</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Intensive Care Medicine, Royal Victoria Hospital, Belfast, Northern Ireland, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>O'Kane</LastName><ForeName>Cecilia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nichol</LastName><ForeName>Alistair</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Clinical Research Centre at St Vincent's University Hospital, University College Dublin, Dublin, Ireland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Intensive Care Unit, Alfred Hospital, Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dos Santos</LastName><ForeName>Claudia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Keenan Research Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rocco</LastName><ForeName>Patricia R M</ForeName><Initials>PRM</Initials><AffiliationInfo><Affiliation>Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bellani</LastName><ForeName>Giacomo</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laffey</LastName><ForeName>John G</ForeName><Initials>JG</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-1246-9573</Identifier><AffiliationInfo><Affiliation>Lung Biology Group, Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland, Galway, Ireland. john.laffey@nuigalway.ie.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway, Ireland. john.laffey@nuigalway.ie.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>07</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Intensive Care Med</MedlineTA><NlmUniqueID>7704851</NlmUniqueID><ISSNLinking>0342-4642</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Acute respiratory distress syndrome</Keyword><Keyword MajorTopicYN="N">Acute respiratory failure</Keyword><Keyword MajorTopicYN="N">Coronavirus</Keyword><Keyword MajorTopicYN="N">Mesenchymal stromal cells</Keyword><Keyword MajorTopicYN="N">Pharmacologic therapy</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>05</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>05</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>7</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>7</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32654006</ArticleId><ArticleId IdType="doi">10.1007/s00134-020-06141-z</ArticleId><ArticleId IdType="pii">10.1007/s00134-020-06141-z</ArticleId><ArticleId IdType="pmc">PMC7352097</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>Brésil</li><li>Canada</li><li>France</li><li>Irlande (pays)</li><li>Italie</li><li>Royaume-Uni</li></country><region><li>Ontario</li><li>Victoria (État)</li><li>État de Rio de Janeiro</li></region><settlement><li>Melbourne</li><li>Rio de Janeiro</li><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Irlande (pays)"><noRegion><name sortKey="Horie, Shahd" sort="Horie, Shahd" uniqKey="Horie S" first="Shahd" last="Horie">Shahd Horie</name></noRegion><name sortKey="Curley, Ger" sort="Curley, Ger" uniqKey="Curley G" first="Ger" last="Curley">Ger Curley</name><name sortKey="Laffey, John G" sort="Laffey, John G" uniqKey="Laffey J" first="John G" last="Laffey">John G. 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