The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness.


Journal

Critical care medicine
ISSN: 1530-0293
Titre abrégé: Crit Care Med
Pays: United States
ID NLM: 0355501

Informations de publication

Date de publication:
01 04 2021
Historique:
pubmed: 17 2 2021
medline: 31 3 2021
entrez: 16 2 2021
Statut: ppublish

Résumé

To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.

Identifiants

pubmed: 33591008
doi: 10.1097/CCM.0000000000004895
pii: 00003246-202104000-00005
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

598-622

Informations de copyright

Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Déclaration de conflit d'intérêts

Dr. Deutschman is past president of the Society of Critical Care Medicine, is a scientific editor for Critical Care Medicine, and is a consultant for Enlivex and Lowell Therapeutics; his institution received funding from National Institute of General Medical Sciences; he received funding from the Society of Critical Care Medicine, Elsevier, Enlivex, Sage Therapeutics, and La Jolla Pharmaceuticals; and he received support for article research from the National Institutes of Health (NIH). Dr. Evans disclosed that she serves as the cochair of the Surviving Sepsis Committee and as the adult Surviving Sepsis Campaign Guidelines for the management of sepsis and septic shock. Dr. Ferrer received funding from MSD, Pfizer, and Gilead. Dr. Kesecioglu is president of the European Society of Intensive Care Medicine. Dr. Kissoon is the pediatrics guidelines cochair of the Surviving Sepsis Committee. Dr. Martin-Loeches received honoraria from MSD, Gilead, and Aspen. Dr. Nunnally is Treasurer of the Society of Critical Care Anesthesiologists. Dr. Prescott is the sepsis lead for a Michigan statewide sepsis quality improvement initiative sponsored by Blue Cross Blue Shield of Michigan, and his institution received funding from Agency for Healthcare Research and Quality, the Department of Veterans Affairs, and the NIH, and she disclosed government work. Dr. Rhodes is the adult guidelines cochair of the Surviving Sepsis Committee and a member of the Executive Committee. Dr. Talmor received speaking fees from Hamilton Medical, Clew, and Mindray. Dr. Tissieres is president of the European Society of Pediatric and Neonatal Intensive Care, is the pediatrics guidelines cochair of the Surviving Sepsis Committee, and has received consulting fees or research grant from Baxter, bioMerieux, Sanofi. Dr. DeBacker is past president of the European Society of Intensive Care Medicine and has received consulting fees from Fresenius Kabi. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Références

COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). 2020. Available at: https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 . Accessed November 25, 2020
Armstrong RA, Kane AD, Cook TM: Decreasing mortality rates in ICU during the COVID-19 pandemic. Anaesthesia 2020 Aug 10. [online ahead of print]
Auld SC, Caridi-Scheible M, Robichaux C, et al.: Declines in mortality over time for critically ill adults with coronavirus disease 2019. Crit Care Med 2020; 48:e1382–e1384
NIH COVID-19 Treatment Guidelines: 2020. Available at: https://www.covid19treatmentguidelines.nih.gov/ . Accessed November 25, 2020
World Health Organization: Therapeutics and COVID-19: living guideline. 2020. Available at: https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline . Accessed November 25, 2020
Alhazzani W, Møller MH, Arabi YM, et al.: Surviving sepsis campaign: Guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med 2020; 48:e440–e469
Alhazzani W, Møller MH, Arabi YM, et al.: Surviving sepsis campaign: Guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med 2020; 46:854–887
Coopersmith CM, De Backer D, Deutschman CS, et al.: Surviving sepsis campaign: Research priorities for sepsis and septic shock. Intensive Care Med 2018; 44:1400–1426
Coopersmith CM, De Backer D, Deutschman CS, et al.: Surviving sepsis campaign: Research priorities for sepsis and septic shock. Crit Care Med 2018; 46:1334–1356
Deutschman CS, Hellman J, Ferrer Roca R, et al.; Research Committee of the Surviving Sepsis Campaign: The surviving sepsis campaign: Basic/translational science research priorities. Crit Care Med 2020; 48:1217–1232
Deutschman CS, Hellman J, Roca RF, et al.; Research Committee of the Surviving Sepsis Campaign: The surviving sepsis campaign: Basic/translational science research priorities. Intensive Care Med Exp 2020; 8:31
Peto R, Abdool Karim Q, Alejandria M, et al.; WHO Solidarity Trial Consortium HP: Repurposed Antiviral Drugs for COVID-19 –Interim WHO SOLIDARITY Trial Results. 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1 . Accessed November 25, 2020
Ranieri VM, Rubenfeld GD, Thompson BT, et al.: Acute respiratory distress syndrome: The Berlin definition. JAMA 2012; 307:2526–2533
Ferrando C, Suarez-Sipmann F, Mellado-Artigas R, et al.: Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS. Intensive Care Med 2020; 46:1–12
Haudebourg AF, Perier F, Tuffet S, et al.: Respiratory mechanics of COVID-19- versus non-COVID-19-associated acute respiratory distress syndrome. Am J Respir Crit Care Med 2020; 202:287–290
Ziehr DR, Alladina J, Petri CR, et al.: Respiratory pathophysiology of mechanically ventilated patients with COVID-19: A cohort study. Am J Respir Crit Care Med 2020; 201:1560–1564
Gattinoni L, Coppola S, Cressoni M, et al.: COVID-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med 2020; 201:1299–1300
Bos LDJ, Sinha P, Dickson RP: The perils of premature phenotyping in COVID-19: A call for caution. Eur Respir J 2020; 56:2001768
Esnault P, Cardinale M, Hraiech S, et al.: High respiratory drive and excessive respiratory efforts predict relapse of respiratory failure in critically ill patients with COVID-19. Am J Respir Crit Care Med 2020; 202:1173–1178
Qin C, Zhou L, Hu Z, et al.: Dysregulation of immune response in patients with Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020; 71:762–768
Sinha P, Matthay MA, Calfee CS: Is a “cytokine storm” relevant to COVID-19? JAMA Intern Med 2020; 180:1152–1154
Kox M, Waalders NJB, Kooistra EJ, et al.: Cytokine levels in critically ill patients with COVID-19 and other conditions. JAMA 2020; 324:1565–1567
Leisman DE, Ronner L, Pinotti R, et al.: Cytokine elevation in severe and critical COVID-19: A rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med 2020; 8:1233–1244
Horby P, Lim WS, Emberson JR, et al.: Dexamethasone in hospitalized patients with COVID-19 - preliminary report. N Engl J Med 2020
Angus DC, Derde L, Al-Beidh F, et al.; Writing Committee for the REMAP-CAP Investigators: Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA 2020; 324:1317–1329
Tomazini BM, Maia IS, Cavalcanti AB, et al.; COALITION COVID-19 Brazil III Investigators: Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: The CoDEX randomized clinical trial. JAMA 2020; 324:1307–1316
Dequin PF, Heming N, Meziani F, et al.; CAPE COVID Trial Group and the CRICS-TriGGERSep Network: Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: A randomized clinical trial. JAMA 2020; 324:1298–1306
Sterne JAC, Murthy S, Diaz JV, et al.: Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis. JAMA 2020; 324:1330–1341
Mathew D, Giles JR, Baxter AE, et al.: Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020; 369:eabc8511
Lucas M, Stuart LM, Savill J, et al.: Apoptotic cells and innate immune stimuli combine to regulate macrophage cytokine secretion. J Immunol 2003; 171:2610–2615
Steinberg KP, Hudson LD, Goodman RB, et al.; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354:1671–1684
Keith P, Day M, Perkins L, et al.: A novel treatment approach to the novel coronavirus: An argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care 2020; 24:128
Yiğenoğlu TN, Ulas T, Dal MS, et al.: Extracorporeal blood purification treatment options for COVID-19: The role of immunoadsorption. Transfus Apher Sci 2020; 59:102855
Wang D, Hu B, Hu C, et al.: Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323:1061–1069
Wang W, Xu Y, Gao R, et al.: Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020; 323:1843–1844
Xiao F, Tang M, Zheng X, et al.: Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020; 158:1831–1833.e3
Tavazzi G, Pellegrini C, Maurelli M, et al.: Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 2020; 22:911–915
Remmelink M, De Mendonça R, D’Haene N, et al.: Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. Crit Care 2020; 24:495
Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al.: Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383:590–592
Su H, Yang M, Wan C, et al.: Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020; 98:219–227
Li W, Moore MJ, Vasilieva N, et al.: Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426:450–454
Matsuyama S, Nagata N, Shirato K, et al.: Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J Virol 2010; 84:12658–12664
Bertram S, Heurich A, Lavender H, et al.: Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts. PLoS One 2012; 7:e35876
Zhao Y, Zhao Z, Wang Y, et al.: Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med 2020; 202:756–759
Zou X, Chen K, Zou J, et al.: Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 2020; 14:185–192
Qi F, Qian S, Zhang S, et al.: Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun 2020; 526:135–140
Zhang H, Li HB, Lyu JR, et al.: Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection. Int J Infect Dis 2020; 96:19–24
Hamming I, Timens W, Bulthuis ML, et al.: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203:631–637
Zhang H, Rostami MR, Leopold PL, et al.: Expression of the SARS-CoV-2 ACE2 receptor in the human airway epithelium. Am J Respir Crit Care Med 2020; 202:219–229
Sungnak W, Huang N, Bécavin C, et al.; HCA Lung Biological Network: SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med 2020; 26:681–687
Radzikowska U, Ding M, Tan G, et al.: Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors. Allergy 2020; 75:2829–2845
Millet JK, Whittaker GR: Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Res 2015; 202:120–134
Simmons G, Gosalia DN, Rennekamp AJ, et al.: Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci U S A 2005; 102:11876–11881
Chu H, Zhou J, Wong BH, et al.: Middle east respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J Infect Dis 2016; 213:904–914
Ziegler CGK, Allon SJ, Nyquist SK, et al.; HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org ; HCA Lung Biological Network: SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 2020; 181:1016–1035.e19
Hoffmann M, Kleine-Weber H, Schroeder S, et al.: SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181:271–280.e8
Wrapp D, Wang N, Corbett KS, et al.: Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367:1260–1263
Wang Q, Ding SL, Li Y, et al.: The allen mouse brain common coordinate framework: A 3D reference atlas. Cell 2020; 181:936–953.e20
Muramatsu T: Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners. J Biochem 2016; 159:481–490
Chen Z, Mi L, Xu J, et al.: Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus. J Infect Dis 2005; 191:755–760
Klok FA, Kruip MJHA, van der Meer NJM, et al.: Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thromb Res 2020; 191:148–150
Manolis AS, Manolis AA, Manolis TA, et al.: COVID-19 infection and cardiac arrhythmias. Trends Cardiovasc Med 2020; 30:451–460
Cheng Y, Luo R, Wang K, et al.: Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020; 97:829–838
Yang X, Yu Y, Xu J, et al.: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020; 8:475–481
Martinez-Rojas MA, Vega-Vega O, Bobadilla NA: Is the kidney a target of SARS-CoV-2? Am J Physiol Renal Physiol 2020; 318:F1454–F1462
Diamond B: The renin-angiotensin system: An integrated view of lung disease and coagulopathy in COVID-19 and therapeutic implications. J Exp Med 2020; 217:e20201000
Garland V, Kumar AB, Borum ML: Gastrointestinal and hepatic manifestations of COVID-19: Evolving recognition and need for increased understanding in vulnerable populations. J Natl Med Assoc 2020
Han C, Duan C, Zhang S, et al.: Digestive symptoms in COVID-19 patients with mild disease severity: Clinical presentation, stool viral RNA testing, and outcomes. Am J Gastroenterol 2020; 115:916–923
Jin X, Lian JS, Hu JH, et al.: Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020; 69:1002–1009
Parohan M, Yaghoubi S, Seraji A: Liver injury is associated with severe coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of retrospective studies. Hepatol Res 2020; 50:924–935
El Moheb M, Naar L, Christensen MA, et al.: Gastrointestinal complications in critically ill patients with and without COVID-19. JAMA 2020; 324:1899–1901
Hoffmann M, Schroeder S, Kleine-Weber H, et al.: Nafamostat mesylate blocks activation of SARS-CoV-2: New treatment option for COVID-19. Antimicrob Agents Chemother 2020; 64:e00754–20
Doi K, Ikeda M, Hayase N, et al.; COVID-UTH Study Group: Nafamostat mesylate treatment in combination with favipiravir for patients critically ill with COVID-19: A case series. Crit Care 2020; 24:392
Tanaka Y, Sato Y, Sasaki T: Suppression of coronavirus replication by cyclophilin inhibitors. Viruses 2013; 5:1250–1260
van Doremalen N, Miazgowicz KL, Milne-Price S, et al.: Host species restriction of middle east respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J Virol 2014; 88:9220–9232
Wu C, Chen X, Cai Y, et al.: Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020; 180:934–943
Yuki K, Fujiogi M, Koutsogiannaki S: COVID-19 pathophysiology: A review. Clin Immunol 2020; 215:108427
Fan E, Beitler JR, Brochard L, et al.: COVID-19-associated acute respiratory distress syndrome: Is a different approach to management warranted? Lancet Respir Med 2020; 8:816–821
Tan L, Kang X, Ji X, et al.: Validation of predictors of disease severity and outcomes in COVID-19 patients: A descriptive and retrospective study. Med (N Y) 2020; 1:128–138.e3
Grasselli G, Greco M, Zanella A, et al.: Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med 2020; 180:1345–1355
Wadhera RK, Wadhera P, Gaba P, et al.: Variation in COVID-19 hospitalizations and deaths across New York city boroughs. JAMA 2020; 323:2192–2195
Yehia BR, Winegar A, Fogel R, et al.: Association of race with mortality among patients hospitalized with coronavirus disease 2019 (COVID-19) at 92 US hospitals. JAMA Netw Open 2020; 3:e2018039
Lu X, Gong W, Peng Z, et al.: High resolution CT imaging dynamic follow-up study of novel coronavirus pneumonia. Front Med (Lausanne) 2020; 7:168
Lichter Y, Topilsky Y, Taieb P, et al.: Lung ultrasound predicts clinical course and outcomes in COVID-19 patients. Intensive Care Med 2020; 46:1–11
Ellinghaus D, Degenhardt F, Bujanda L, et al.: Genomewide association study of severe COVID-19 with respiratory failure. N Engl J Med 2020; 383:1522–1534
Laing AG, Lorenc A, Del Molino Del Barrio I, et al.: Author correction: A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med 2020; 26:1951
WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection: A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020; 20:e192–e197
Kermali M, Khalsa RK, Pillai K, et al.: The role of biomarkers in diagnosis of COVID-19 - a systematic review. Life Sci 2020; 254:117788
Shang Y, Liu T, Wei Y, et al.: Scoring systems for predicting mortality for severe patients with COVID-19. EClinicalMedicine 2020; 24:100426
Immovilli P, Morelli N, Antonucci E, et al.: COVID-19 mortality and ICU admission: The Italian experience. Crit Care 2020; 24:228
Gupta S, Hayek SS, Wang W, et al.: Factors associated with death in critically ill patients with coronavirus disease 2019 in the US. JAMA Intern Med 2020; 180:1–12
Auld SC, Caridi-Scheible M, Blum JM, et al.; Emory COVID-19 Quality and Clinical Research Collaborative: ICU and ventilator mortality among critically ill adults with coronavirus disease 2019. Crit Care Med 2020; 48:e799–e804
Guérin C, Reignier J, Richard JC, et al.; PROSEVA Study Group: Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368:2159–2168
Munshi L, Del Sorbo L, Adhikari NKJ, et al.: Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc 2017; 14:S280–S288
Fagiuoli S, Lorini FL, Remuzzi G; Covid-19 Bergamo Hospital Crisis Unit: Adaptations and lessons in the Province of Bergamo. N Engl J Med 2020; 382:e71
Grasselli G, Zangrillo A, Zanella A, et al.; COVID-19 Lombardy ICU Network: Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA 2020; 323:1574–1581
Coppo A, Bellani G, Winterton D, et al.: Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): A prospective cohort study. Lancet Respir Med 2020; 8:765–774
Elharrar X, Trigui Y, Dols AM, et al.: Use of prone positioning in nonintubated patients with COVID-19 and hypoxemic acute respiratory failure. JAMA 2020; 323:2336–2338
Sartini C, Tresoldi M, Scarpellini P, et al.: Respiratory parameters in patients with COVID-19 after using noninvasive ventilation in the prone position outside the intensive care unit. JAMA 2020; 323:2338–2340
Xu Q, Wang T, Qin X, et al.: Early awake prone position combined with high-flow nasal oxygen therapy in severe COVID-19: A case series. Crit Care 2020; 24:250
Taboada M, González M, Álvarez A, et al.: Effectiveness of prone positioning in nonintubated intensive care unit patients with moderate to severe acute respiratory distress syndrome by coronavirus disease 2019. Anesth Analg 2021; 132:25–30
Paul V, Patel S, Royse M, et al.: Proning in non-intubated (PINI) in times of COVID-19: Case series and a review. J Intensive Care Med 2020; 35:818–824
Ng Z, Tay WC, Ho CHB: Awake prone positioning for non-intubated oxygen dependent COVID-19 pneumonia patients. Eur Respir J 2020; 56:2001198
Thompson AE, Ranard BL, Wei Y, et al.: Prone positioning in awake, nonintubated patients with COVID-19 hypoxemic respiratory failure. JAMA Intern Med 2020; 180:1537–1539
Ferrando C, Mellado-Artigas R, Gea A, et al.; COVID-19 Spanish ICU Network: Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: A multicenter, adjusted cohort study. Crit Care 2020; 24:597
Ripoll-Gallardo A, Grillenzoni L, Bollon J, et al.: Prone positioning in non-intubated patients with COVID-19 outside of the intensive care unit: More evidence needed. Disaster Med Public Health Prep 2020; 14:1–3
Tchesnokov EP, Feng JY, Porter DP, et al.: Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses 2019; 11;326
Beigel JH, Tomashek KM, Dodd LE, et al.: Remdesivir for the treatment of COVID-19 - preliminary report. N Engl J Med 2020
Goldman JD, Lye DCB, Hui DS, et al.: Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med 2020
Wang Y, Zhang D, Du G, et al.: Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020; 395:1569–1578
Cavalcanti AB, Zampieri FG, Rosa RG, et al.: Hydroxychloroquine with or without azithromycin in mild-to-moderate COVID-19. N Engl J Med 2020
Geleris J, Sun Y, Platt J, et al.: Observational study of hydroxychloroquine in hospitalized patients with COVID-19. N Engl J Med 2020; 382:2411–2418
Rosenberg ES, Dufort EM, Udo T, et al.: Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA 2020; 323:2493–2502
Wang X, Guo X, Xin Q, et al.: Neutralizing antibodies responses to SARS-CoV-2 in COVID-19 inpatients and convalescent patients. Clin Infect Dis 2020: ciaa721
Li L, Zhang W, Hu Y, et al.: Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: A randomized clinical trial. JAMA 2020; 324:460–470
U.S. Food and Drug Administration: Emergency Use Authorization of Medical Products and Related Authorities: Guidance for Industry and Other Stakeholders. Available at: https://www.fda.gov/media/97321/download . Accessed November 25, 2020
Croxtall JD, Perry CM: Lopinavir/ritonavir: A review of its use in the management of HIV-1 infection. Drugs 2010; 70:1885–1915
Baden LR, Rubin EJ: COVID-19 - the search for effective therapy. N Engl J Med 2020; 382:1851–1852
Cao B, Wang Y, Wen D, et al.: A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med 2020; 382:1787–1799
Schoergenhofer C, Jilma B, Stimpfl T, et al.: Pharmacokinetics of lopinavir and ritonavir in patients hospitalized with coronavirus disease 2019 (COVID-19). Ann Intern Med 2020; 173:670–672
Yang SNY, Atkinson SC, Wang C, et al.: The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Res 2020; 177:104760
Caly L, Druce JD, Catton MG, et al.: The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro . Antiviral Res 2020; 178:104787
Chaccour C, Hammann F, Ramón-García S, et al.: Ivermectin and COVID-19: Keeping rigor in times of urgency. Am J Trop Med Hyg 2020; 102:1156–1157
Guzzo CA, Furtek CI, Porras AG, et al.: Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol 2002; 42:1122–1133
Arshad U, Pertinez H, Box H, et al.: Prioritization of anti-SARS-Cov-2 drug repurposing opportunities based on plasma and target site concentrations derived from their established human pharmacokinetics. Clin Pharmacol Ther 2020; 108:775–790
Zhang H, Zhang X, Hou Z, et al.: RhACE2 - playing an important role in inhibiting apoptosis induced by Ang II in HUVECs. Medicine (Baltimore) 2019; 98:e15799
Zhu L, Carretero OA, Xu J, et al.: Activation of angiotensin II type 2 receptor suppresses TNF-α-induced ICAM-1 via NF-кB: Possible role of ACE2. Am J Physiol Heart Circ Physiol 2015; 309:H827–H834
Monteil V, Kwon H, Prado P, et al.: Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; 181:905–913.e7
Varga Z, Flammer AJ, Steiger P, et al.: Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395:1417–1418
Magro C, Mulvey JJ, Berlin D, et al.: Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res 2020; 220:1–13
Ackermann M, Verleden SE, Kuehnel M, et al.: Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 2020; 383:120–128
Carsana L, Sonzogni A, Nasr A, et al.: Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: A two-centre descriptive study. Lancet Infect Dis 2020; 20:1135–1140
Rapkiewicz AV, Mai X, Carsons SE, et al.: Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series. EClinicalMedicine 2020; 24:100434
Goshua G, Pine AB, Meizlish ML, et al.: Endotheliopathy in COVID-19-associated coagulopathy: Evidence from a single-centre, cross-sectional study. Lancet Haematol 2020; 7:e575–e582
Gralinski LE, Sheahan TP, Morrison TE, et al.: Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio 2018; 9:e01753–18
Cui S, Chen S, Li X, et al.: Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020; 18:1421–1424
Zhou F, Yu T, Du R, et al.: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020; 395:1054–1062
Lodigiani C, Iapichino G, Carenzo L, et al.; Humanitas COVID-19 Task Force: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020; 191:9–14
Richardson S, Hirsch JS, Narasimhan M, et al.; the Northwell COVID-19 Research Consortium: Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. JAMA 2020; 323:2052–2059
Connors JM, Levy JH: COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135:2033–2040
Llitjos JF, Leclerc M, Chochois C, et al.: High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost 2020; 18:1743–1746
Oxley TJ, Mocco J, Majidi S, et al.: Large-vessel stroke as a presenting feature of COVID-19 in the young. N Engl J Med 2020; 382:e60
Miesbach W, Makris M: COVID-19: Coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost 2020; 26:1076029620938149
Wang T, Chen R, Liu C, et al.: Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19. Lancet Haematol 2020; 7:e362–e363
Zhang L, Yan X, Fan Q, et al.: D-dimer levels on admission to predict in-hospital mortality in patients with COVID-19. J Thromb Haemost 2020; 18:1324–1329
Yin S, Huang M, Li D, et al.: Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. J Thromb Thrombolysis 2020: 1–4
Zhang Y, Xiao M, Zhang S, et al.: Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med 2020; 382:e38
Panigada M, Bottino N, Tagliabue P, et al.: Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost 2020; 18:1738–1742
Jain R, Young M, Dogra S, et al.: COVID-19 related neuroimaging findings: A signal of thromboembolic complications and a strong prognostic marker of poor patient outcome. J Neurol Sci 2020; 414:116923
Nadkarni GN, Lala A, Bagiella E, et al.: Anticoagulation, bleeding, mortality, and pathology in hospitalized patients with COVID-19. J Am Coll Cardiol 2020; 76:1815–1826
Barco S, Bingisser R, Colucci G, et al.: Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): A structured summary of a study protocol for a randomized controlled trial. Trials 2020; 21:770
Kharma N, Roehrig S, Shible AA, et al.: Anticoagulation in critically ill patients on mechanical ventilation suffering from COVID-19 disease, the ANTI-CO trial: A structured summary of a study protocol for a randomised controlled trial. Trials 2020; 21:769
Houston BL, Lawler PR, Goligher EC, et al.: Anti-thrombotic therapy to ameliorate complications of COVID-19 (ATTACC): Study design and methodology for an international, adaptive Bayesian randomized controlled trial. Clin Trials 2020; 17:491–500
Busani S, Tosi M, Mighali P, et al.: Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial. Trials 2020; 21:724
Thachil J, Tang N, Gando S, et al.: ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020; 18:1023–1026
Becker RC: Covid-19 treatment update: Follow the scientific evidence. J Thromb Thrombolysis 2020; 50:43–53
Tang N, Bai H, Chen X, et al.: Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18:1094–1099
Bikdeli B, Madhavan MV, Jimenez D, et al.; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function: COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75:2950–2973
Dogra S, Jain R, Cao M, et al.: Hemorrhagic stroke and anticoagulation in COVID-19. J Stroke Cerebrovasc Dis 2020; 29:104984
Iba T, Levy JH, Levi M, et al.: Coagulopathy of coronavirus disease 2019. Crit Care Med 2020; 48:1358–1364
Helms J, Tacquard C, Severac F, et al.; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis): High risk of thrombosis in patients with severe SARS-CoV-2 infection: A multicenter prospective cohort study. Intensive Care Med 2020; 46:1089–1098
Middeldorp S, Coppens M, van Haaps TF, et al.: Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020; 18:1995–2002
Klok FA, Kruip MJHA, van der Meer NJM, et al.: Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020; 191:145–147
Kashi M, Jacquin A, Dakhil B, et al.: Severe arterial thrombosis associated with Covid-19 infection. Thromb Res 2020; 192:75–77
Buja LM, Wolf DA, Zhao B, et al.: The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities. Cardiovasc Pathol 2020; 48:107233
Ranucci M, Ballotta A, Di Dedda U, et al.: The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost 2020; 18:1747–1751
Gris JC, Loubet P, Roger C, et al.: The association between D-dimers in COVID-19 patients and mortality remains beset of uncertainties. J Thromb Haemost 2020; 18:2068–2070
Siguret V, Voicu S, Neuwirth M, et al.: Are antiphospholipid antibodies associated with thrombotic complications in critically ill COVID-19 patients? Thromb Res 2020; 195:74–76
Li Y, Zhao K, Wei H, et al.: Dynamic relationship between D-dimer and COVID-19 severity. Br J Haematol 2020; 190:e24–e27
Maier CL, Truong AD, Auld SC, et al.: COVID-19-associated hyperviscosity: A link between inflammation and thrombophilia? Lancet 2020; 395:1758–1759
Creel-Bulos C, Auld SC, Caridi-Scheible M, et al.: Fibrinolysis shutdown and thrombosis in a COVID-19 ICU. Shock 2020
Joly BS, Siguret V, Veyradier A: Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19. Intensive Care Med 2020; 46:1603–1606
Han H, Yang L, Liu R, et al.: Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med 2020; 58:1116–1120
Campbell CM, Kahwash R: Will complement inhibition be the new target in treating COVID-19-related systemic thrombosis? Circulation 2020; 141:1739–1741
Lippi G, Plebani M, Henry BM: Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta 2020; 506:145–148
Prescott HC, Angus DC: Enhancing recovery from sepsis: A review. JAMA 2018; 319:62–75
Needham DM, Davidson J, Cohen H, et al.: Improving long-term outcomes after discharge from intensive care unit: Report from a stakeholders’ conference. Crit Care Med 2012; 40:502–509
McPeake J, Mikkelsen ME, Quasim T, et al.: Return to employment after critical illness and its association with psychosocial outcomes. A systematic review and meta-analysis. Ann Am Thorac Soc 2019; 16:1304–1311
Yende S, Austin S, Rhodes A, et al.: Long-term quality of life among survivors of severe sepsis: Analyses of two international trials. Crit Care Med 2016; 44:1461–1467
Ahmed H, Patel K, Greenwood DC, et al.: Long-term clinical outcomes in survivors of severe acute respiratory syndrome and middle east respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis. J Rehabil Med 2020; 52:jrm00063
Hosey MM, Needham DM: Survivorship after COVID-19 ICU stay. Nat Rev Dis Primers 2020; 6:60
Thornton J: COVID-19: The challenge of patient rehabilitation after intensive care. BMJ 2020; 369:m1787
Carfi A, Bernabei R, Landi F: Persistent symptoms in patients after acute COVID-19. JAMA 2020; 324:603–605
Chopra V, Flanders SA, O’Malley M, et al.: Sixty-day outcomes among patients hospitalized with COVID-19. Ann Intern Med 2020
Smith-Spark L, Shelly J, Borghese L: Brain Fog, Fatigue, Breathlessness. Rehab Centers Set Up Across Europe to Treat Long-Term Effects of Coronavirus: CNN, 2020. Available at: https://www.cnn.com/2020/07/19/health/long-covid-italy-uk-gbr-intl/index.html . Accessed November 25, 2020
Long COVID 2020: Available at: https://www.longcovid.org
Prescott HC, Iwashyna TJ, Blackwood B, et al.: Understanding and enhancing sepsis survivorship. Priorities for research and practice. Am J Respir Crit Care Med 2019; 200:972–981
Chen Z, John Wherry E: T cell responses in patients with COVID-19. Nat Rev Immunol 2020; 20:529–536
Silvin A, Chapuis N, Dunsmore G, et al.: Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell 2020; 182:1401–1418.e18
McGonagle D, Sharif K, O’Regan A, et al.: The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 2020; 19:102537
Lucas C, Wong P, Klein J, et al.; Yale IMPACT Team: Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020; 584:463–469
Liao M, Liu Y, Yuan J, et al.: Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med 2020; 26:842–844
Kuri-Cervantes L, Pampena MB, Meng W, et al.: Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci Immunol 2020; 5;eabd7114
Cossarizza A, Gibellini L, De Biasi S, et al.: Handling and processing of blood specimens from patients with COVID-19 for safe studies on cell phenotype and cytokine storm. Cytometry A 2020; 97:668–673
Diao B, Wang C, Tan Y, et al.: Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol 2020; 11:827
Allegra A, Di Gioacchino M, Tonacci A, et al.: Immunopathology of SARS-CoV-2 infection: Immune cells and mediators, prognostic factors, and immune-therapeutic implications. Int J Mol Sci 2020; 21:4782
Schulte-Schrepping J, Reusch N, Paclik D, et al.; Deutsche COVID-19 OMICS Initiative (DeCOI): Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell 2020; 182:1419–1440.e23
Drifte G, Dunn-Siegrist I, Tissières P, et al.: Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome. Crit Care Med 2013; 41:820–832
Zuo Y, Yalavarthi S, Shi H, et al.: Neutrophil extracellular traps in COVID-19. JCI Insight 2020; 5:e138999
Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al.: Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med 2020; 217:e20200652
Tissières P, Teboul JL: SARS-CoV-2 post-infective myocarditis: The tip of COVID-19 immune complications? Ann Intensive Care 2020; 10:98
Bastard P, Rosen LB, Zhang Q, et al.: Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020; 370:eabd4585
Lee PY, Day-Lewis M, Henderson LA, et al.: Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest 2020; 130:5942–5950
Belhadjer Z, Auriau J, Méot M, et al.: Addition of corticosteroids to immunoglobulins is associated with recovery of cardiac function in multi-inflammatory syndrome in children. Circulation 2020; 142:2282–2284
Suleyman G, Fadel RA, Malette KM, et al.: Clinical characteristics and morbidity associated with coronavirus disease 2019 in a series of patients in metropolitan detroit. JAMA Netw Open 2020; 3:e2012270
Liu J, Zhang S, Wu Z, et al.: Clinical outcomes of COVID-19 in Wuhan, China: A large cohort study. Ann Intensive Care 2020; 10:99
Wang W, Zhao Z, Liu X, et al.: Clinical features and potential risk factors for discerning the critical cases and predicting the outcome of patients with COVID-19. J Clin Lab Anal 2020; 34:e23547
Borghesi A, Maroldi R: COVID-19 outbreak in Italy: Experimental chest X-ray scoring system for quantifying and monitoring disease progression. Radiol Med 2020; 125:509–513
Prebensen C, Hre PLM, Jonassen C, et al.: SARS-CoV-2 RNA in plasma is associated with ICU admission and mortality in patients hospitalized with COVID-19. Clin Infect Dis 2020
Liang W, Liang H, Ou L, et al.; China Medical Treatment Expert Group for COVID-19: Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. JAMA Intern Med 2020; 180:1081–1089
Liu FY, Sun XL, Zhang Y, et al.: Evaluation of the risk prediction tools for patients with coronavirus disease 2019 in Wuhan, China: A single-centered, retrospective, observational study. Crit Care Med 2020; 48:e1004–e1011
Zhao Z, Chen A, Hou W, et al.: Prediction model and risk scores of ICU admission and mortality in COVID-19. PLoS One 2020; 15:e0236618
Altman DG: The scandal of poor medical research. BMJ 1994; 308:283–284
Cook D, Burns K, Finfer S, et al.: Clinical research ethics for critically ill patients: A pandemic proposal. Crit Care Med 2010; 38:e138–e142
Sattui SE, Liew JW, Graef ER, et al.: Swinging the pendulum: Lessons learned from public discourse concerning hydroxychloroquine and COVID-19. Expert Rev Clin Immunol 2020; 16:659–666
Citerio G, Bakker J, Brochard L, et al.: Critical care journals during the COVID-19 pandemic: Challenges and responsibilities. Intensive Care Med 2020; 46:1521–1523
Kaplan LJ, Bleck TP, Buchman TG, et al.: Pandemic-related submissions: The challenge of discerning signal amidst noise. Crit Care Med 2020; 48:1099–1102
Ezequiel G, Jafet A, Hugo A, et al.: The COVID-19 pandemic: A call to action for health systems in Latin America to strengthen quality of care. Int J Qual Health Care 2020: mzaa062
Camporota L, Vasques F, Sanderson B, et al.: Identification of pathophysiological patterns for triage and respiratory support in COVID-19. Lancet Respir Med 2020; 8:752–754
Baker T, Schell CO, Petersen DB, et al.: Essential care of critical illness must not be forgotten in the COVID-19 pandemic. Lancet 2020; 395:1253–1254
Retsas S: Clinical trials and the COVID-19 pandemic. Hell J Nucl Med 2020; 23:4–5
Fitzsimons J: Quality & safety in the time of coronavirus-design better, learn faster. Int J Qual Health Care 2020
Zhang T, He Y, Xu W, et al.: Clinical trials for the treatment of coronavirus disease 2019 (COVID-19): A rapid response to urgent need. Sci China Life Sci 2020; 63:774–776
Wendler D, Rid A: In defense of a social value requirement for clinical research. Bioethics 2017; 31:77–86
Barnbaum DR: Data safety monitoring during COVID-19: Keep on keeping on. Ethics Hum Res 2020; 42:43–44
Zhang H, Shao F, Gu J, et al.: Ethics committee reviews of applications for research studies at 1 hospital in China during the 2019 novel Coronavirus epidemic. JAMA 2020; 323:1844–1846
Loree JM, Anand S, Dasari A, et al.: Disparity of race reporting and representation in clinical trials leading to cancer drug approvals from 2008 to 2018. JAMA Oncol 2019; 5:e191870
Cook DJ, Kho ME, Duan EH, et al.: Principles guiding nonpandemic critical care research during a pandemic. Crit Care Med 2020; 48:1403–1410
Saitz R, Schwitzer G: Communicating science in the time of a pandemic. JAMA 2020; 324:443–444
Addis A, Genazzani A, Trotta MP, et al.: Promoting better clinical trials and drug information as public health interventions for the COVID-19 emergency in Italy. Ann Intern Med 2020; 173:654–655
Eysenbach G: How to fight an infodemic: The four pillars of infodemic management. J Med Internet Res 2020; 22:e21820

Auteurs

Craig M Coopersmith (CM)

Department of Surgery and Emory Critical Care Center, Emory University, Atlanta, GA.

Massimo Antonelli (M)

Department of Anesthesiology Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Italy.

Seth R Bauer (SR)

Department of Pharmacy, Cleveland Clinic, Cleveland, OH.

Clifford S Deutschman (CS)

Department of Pediatrics, Cohen Children's Medical center, Northwell Health, New Hyde Park, NY.
Feinstein Institute for Medical Research/Elmezzi Graduate School of Molecular Medicine, Manhasset, NY.

Laura E Evans (LE)

Department of Medicine, University of Washington, Seattle, WA.

Ricard Ferrer (R)

Department of Intensive Care, SODIR-VHIR Research Group, Vall d'Hebron University Hospital, Barcelona, Spain.

Judith Hellman (J)

Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA.

Sameer Jog (S)

Department of Intensive Care Medicine, Deenanath Mangeshkar Hospital, Pune, India.

Jozef Kesecioglu (J)

Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

Niranjan Kissoon (N)

Department of Pediatrics and Emergency Medicine, University of British Columbia, Vancouver, BC, Canada.

Ignacio Martin-Loeches (I)

Multidisciplinary Intensive Care Research Organization (MICRO), Department of Intensive Care Medicine, St. James's University Hospital, Trinity Centre for Health Sciences, Dublin, Ireland.
Hospital Clinic, IDIBAPS, Universided de Barcelona, CIBERes, Barcelona, Spain.

Mark E Nunnally (ME)

Departments of Anesthesiology, Perioperative Care and Pain Medicine, Neurology, Surgery and Medicine, New York University, New York, NY.

Hallie C Prescott (HC)

Department of Medicine, University of Michigan and VA Center for Clinical Management Research, Ann Arbor, MI.

Andrew Rhodes (A)

St George's University Hospitals NHS Foundation Trust and St George's University of London, London, United Kingdom.

Daniel Talmor (D)

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.

Pierre Tissieres (P)

Pediatric Intensive Care, AP-HP Paris Saclay University, Le Kremlin-Bicetre and Institute of Integrative Biology of the Cell, CNRS, CEA, Paris-Saclay University, Gif-sur-Yvette, France.

Daniel De Backer (D)

Chirec Hospitals, Université Libre de Bruxelles, Brussels, Belgium.

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