TY - JOUR
T1 - Prevalence of phenotypes of acute respiratory distress syndrome in critically ill patients with COVID-19
T2 - a prospective observational study
AU - Sinha, Pratik
AU - Calfee, Carolyn S.
AU - Cherian, Shiney
AU - Brealey, David
AU - Cutler, Sean
AU - King, Charles
AU - Killick, Charlotte
AU - Richards, Owen
AU - Cheema, Yusuf
AU - Bailey, Catherine
AU - Reddy, Kiran
AU - Delucchi, Kevin L.
AU - Shankar-Hari, Manu
AU - Gordon, Anthony C.
AU - Shyamsundar, Murali
AU - O'Kane, Cecilia M.
AU - McAuley, Daniel F.
AU - Szakmany, Tamas
N1 - Funding Information:
CSC reports grants from the US National Institutes of Health (NIH), during the conduct of the study; grants from Roche/Genentech and Bayer, outside the submitted work; and personal fees for consultancy from Quark Pharmaceuticals, Vasomune, and Gen1e Life Sciences, outside the submitted work. ACG reports funding through a UK National Institute for Health Research (NIHR) Research Professorship, during the conduct of the study; and fees for consultancy, paid to his institution, from Bristol-Meyers Squibb and GlaxoSmithKline (GSK), outside the submitted work. CMO'K reports grants from Innovate UK, during the conduct of the study; and grants from NIHR, the Wellcome Trust, the UK Medical Research Council, Northern Ireland (NI) Health and Social care R&D Division, NI Chest Heart and Stroke, and Medical Research Council, outside the submitted work. DFM reports a grant from Innovate UK for the conduct of the phenotypes in the acute respiratory distress syndrome (PHIND) study; and personal fees for consultancy from GSK, Boehringer Ingelheim, and Bayer, outside the submitted work. DFM's institution has received grants from the NIHR, the Wellcome Trust, NI Health and Social care R&D Division, NI Chest Heart and Stroke, and Medical Research Council; DFM has a patent issued to his institution for a treatment for acute respiratory distress syndrome. DFM is a Director of Research for the Intensive Care Society and NIHR Efficacy and Mechanism Evaluation Programme Director. All other authors declare no competing interests.
Funding Information:
This publication presents independent research funded by the US NIH, grant numbers GM008440?21 (PS) and HL140026 (CSC), and Innovate UK (reference 104639). Randox funded the development of the point-of-care assay. MS-H is funded by an NIHR Clinician Scientist Award. ACG is funded by an NIHR Research Professorship (RP-2015-06-18) and supported by the NIHR Imperial Biomedical Research Centre. We thank the staff of the Northern Ireland Clinical Trials Unit for their support in conducting the study. We thank Jeremy Parker, John Lamont, and the staff at Randox for their role in the development of the point-of-care assay. We would also like to thank the patients and staff at the two hospitals from which these data originated: The Royal Gwent Hospital, Newport and University College Hospital, London. The views expressed are those of the author(s) and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health and Social Care.
Funding Information:
This publication presents independent research funded by the US NIH, grant numbers GM008440–21 (PS) and HL140026 (CSC), and Innovate UK (reference 104639). Randox funded the development of the point-of-care assay. MS-H is funded by an NIHR Clinician Scientist Award. ACG is funded by an NIHR Research Professorship (RP-2015-06-18) and supported by the NIHR Imperial Biomedical Research Centre. We thank the staff of the Northern Ireland Clinical Trials Unit for their support in conducting the study. We thank Jeremy Parker, John Lamont, and the staff at Randox for their role in the development of the point-of-care assay. We would also like to thank the patients and staff at the two hospitals from which these data originated: The Royal Gwent Hospital, Newport and University College Hospital, London. The views expressed are those of the author(s) and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health and Social Care.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/12
Y1 - 2020/12
N2 - Background: In acute respiratory distress syndrome (ARDS) unrelated to COVID-19, two phenotypes, based on the severity of systemic inflammation (hyperinflammatory and hypoinflammatory), have been described. The hyperinflammatory phenotype is known to be associated with increased multiorgan failure and mortality. In this study, we aimed to identify these phenotypes in COVID-19-related ARDS. Methods: In this prospective observational study done at two UK intensive care units, we recruited patients with ARDS due to COVID-19. Demographic, clinical, and laboratory data were collected at baseline. Plasma samples were analysed for interleukin-6 (IL-6) and soluble tumour necrosis factor receptor superfamily member 1A (TNFR1) using a novel point-of-care assay. A parsimonious regression classifier model was used to calculate the probability for the hyperinflammatory phenotype in COVID-19 using IL-6, soluble TNFR1, and bicarbonate levels. Data from this cohort was compared with patients with ARDS due to causes other than COVID-19 recruited to a previous UK multicentre, randomised controlled trial of simvastatin (HARP-2). Findings: Between March 17 and April 25, 2020, 39 patients were recruited to the study. Median ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) was 18 kpa (IQR 15–21) and acute physiology and chronic health evaluation II score was 12 (10–16). 17 (44%) of 39 patients had died by day 28 of the study. Compared with survivors, patients who died were older and had lower PaO2/FiO2. The median probability for the hyperinflammatory phenotype was 0·03 (IQR 0·01–0·2). Depending on the probability cutoff used to assign class, the prevalence of the hyperinflammatory phenotype was between four (10%) and eight (21%) of 39, which is lower than the proportion of patients with the hyperinflammatory phenotype in HARP-2 (186 [35%] of 539). Using the Youden index cutoff (0·274) to classify phenotype, five (63%) of eight patients with the hyperinflammatory phenotype and 12 (39%) of 31 with the hypoinflammatory phenotype died. Compared with matched patients recruited to HARP-2, levels of IL-6 were similar in our cohort, whereas soluble TNFR1 was significantly lower in patients with COVID-19-associated ARDS. Interpretation: In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model. Funding: US National Institutes of Health, Innovate UK, and Randox.
AB - Background: In acute respiratory distress syndrome (ARDS) unrelated to COVID-19, two phenotypes, based on the severity of systemic inflammation (hyperinflammatory and hypoinflammatory), have been described. The hyperinflammatory phenotype is known to be associated with increased multiorgan failure and mortality. In this study, we aimed to identify these phenotypes in COVID-19-related ARDS. Methods: In this prospective observational study done at two UK intensive care units, we recruited patients with ARDS due to COVID-19. Demographic, clinical, and laboratory data were collected at baseline. Plasma samples were analysed for interleukin-6 (IL-6) and soluble tumour necrosis factor receptor superfamily member 1A (TNFR1) using a novel point-of-care assay. A parsimonious regression classifier model was used to calculate the probability for the hyperinflammatory phenotype in COVID-19 using IL-6, soluble TNFR1, and bicarbonate levels. Data from this cohort was compared with patients with ARDS due to causes other than COVID-19 recruited to a previous UK multicentre, randomised controlled trial of simvastatin (HARP-2). Findings: Between March 17 and April 25, 2020, 39 patients were recruited to the study. Median ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) was 18 kpa (IQR 15–21) and acute physiology and chronic health evaluation II score was 12 (10–16). 17 (44%) of 39 patients had died by day 28 of the study. Compared with survivors, patients who died were older and had lower PaO2/FiO2. The median probability for the hyperinflammatory phenotype was 0·03 (IQR 0·01–0·2). Depending on the probability cutoff used to assign class, the prevalence of the hyperinflammatory phenotype was between four (10%) and eight (21%) of 39, which is lower than the proportion of patients with the hyperinflammatory phenotype in HARP-2 (186 [35%] of 539). Using the Youden index cutoff (0·274) to classify phenotype, five (63%) of eight patients with the hyperinflammatory phenotype and 12 (39%) of 31 with the hypoinflammatory phenotype died. Compared with matched patients recruited to HARP-2, levels of IL-6 were similar in our cohort, whereas soluble TNFR1 was significantly lower in patients with COVID-19-associated ARDS. Interpretation: In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model. Funding: US National Institutes of Health, Innovate UK, and Randox.
UR - http://www.scopus.com/inward/record.url?scp=85090488224&partnerID=8YFLogxK
U2 - 10.1016/S2213-2600(20)30366-0
DO - 10.1016/S2213-2600(20)30366-0
M3 - Article
C2 - 32861275
AN - SCOPUS:85090488224
SN - 2213-2600
VL - 8
SP - 1209
EP - 1218
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 12
ER -