TY - JOUR
T1 - Biomarker Analysis Provides Evidence for Host Response Homogeneity in Patients With COVID-19
AU - van Amstel, Rombout B. E.
AU - Michels, Erik H. A.
AU - Appelman, Brent
AU - de Brabander, Justin
AU - Smeele, Patrick J.
AU - van der Poll, Tom
AU - Vlaar, Alexander P. J.
AU - van Vught, Lonneke A.
AU - Bos, Lieuwe D. J.
AU - van Agtmael, Michiel A.
AU - Algera, Anne G.
AU - van Baarle, Floor E. H. P.
AU - van de Beek, Diederik
AU - Beudel, Martijn
AU - Bogaard, Harm J.
AU - Botta, Michela
AU - de Bree, Godelieve J.
AU - Brouwer, Matthijs C.
AU - de Bruin, Sanne
AU - Bugiani, Marianna
AU - Bulle, Esther B.
AU - Chouchane, Osoul
AU - Cloherty, Alex P. M.
AU - Buis, David
AU - de Rotte, Maurtis C. F. J.
AU - Dijkstra, Mirjam
AU - Dongelmans, Dave A.
AU - Dujardin, Romein W. G.
AU - Elbers, Paul E.
AU - Fleuren, Lucas M.
AU - Geerlings, Suzanne E.
AU - Geijtenbeek, Theo B. H.
AU - Girbes, Armand R. J.
AU - Goorhuis, Bram
AU - Grobusch, Martin P.
AU - Hagens, Laura A.
AU - Hamann, Jorg
AU - Harris, Vanessa C.
AU - Hemke, Robert
AU - Hermans, Sabine M.
AU - Heunks, Leo M. A.
AU - Hollmann, Markus W.
AU - Horn, Janneke
AU - Hovius, Joppe W.
AU - de Jong, Menno D.
AU - Koning, Rutger
AU - Lim, Endry H. T.
AU - van Mourik, Niels
AU - Nellen, Jeannine F.
AU - Nossent, Esther J.
AU - Paulus, Frederique
AU - Peters, Edgar
AU - Piña-Fuentes, Dan
AU - Preckel, Bennedikt
AU - Raasveld, Jorinde
AU - Reijnders, Tom D. Y.
AU - Schinkel, Michiel
AU - Schrauwen, Femke A. P.
AU - Schultz, Marcus J.
AU - Schuurman, Alex R.
AU - Schuurmans, Jaap
AU - Sigaloff, Kim
AU - Slim, Marleen A.
AU - Smeele, Patrick
AU - Smit, Marry R.
AU - Stijnis, Cornelis
AU - Stilma, Willemke
AU - Teunissen, Charlotte E.
AU - Thoral, Patrick
AU - Tsonas, Anissa M.
AU - Tuinman, Pieter R.
AU - van der Valk, Marc
AU - Veelo, Denise P.
AU - Volleman, Carolien
AU - de Vries, Heder
AU - van Vugt, Michèle
AU - Wiersinga, Joost
AU - Wouters, Dorien
AU - Zwinderman, Koos
PY - 2024/6/1
Y1 - 2024/6/1
N2 - Background: The exploration of subphenotypes in hospitalized patients with COVID-19 has garnered substantial attention. Most existing studies operate under the assumption of heterogeneity in COVID-19 patient populations, and this assumption can lead to erroneous conclusions. Research Question: Do plasma biomarker profiles reflective of various pathophysiologic pathways provide evidence for heterogeneity in hospitalized patients with COVID-19? Study Design and Methods: This is a secondary analysis of two prospective observational studies of adult patients hospitalized with COVID-19-related respiratory failure in the general ward and ICU of two medical centers and with 44 host response biomarkers available. Parsimonious models were used to allocate and validate ARDS inflammatory subphenotypes. Novel biological subphenotypes were identified using latent profile analysis (LPA) and hierarchical clustering. Heterogeneity of treatment effect for corticosteroids was assessed using an interaction term in a logistic regression model. Results: The cohort consisted of 162 patients admitted to the ICU and 464 patients admitted to the ward. Using the parsimonious models in ICU patients, only 3.1% to 13% of patients were classified as hyperinflammatory subphenotype. Using de novo subphenotyping techniques, neither clustering nor LPA revealed significant evidence for heterogeneity in the ward (P = .11-.13), ICU (P = .23-.88), or combined cohort (P = .05-.88). Adding clinical variables did not alter results in the ICU or combined cohort. Using the combined approach in the ward cohort, indices provided borderline significance for two subphenotypes, and there was good agreement between clustering and LPA (87.9%), but no heterogeneity of treatment effect for corticosteroids was observed between these two classes (P = .198). Interpretation: Systemic inflammatory subphenotypes derived from patients with ARDS did not reflect the variation in severity of COVID-19 in this study. Empirical evidence, derived from cluster analysis or LPA, offers limited support for biological heterogeneity in COVID-19.
AB - Background: The exploration of subphenotypes in hospitalized patients with COVID-19 has garnered substantial attention. Most existing studies operate under the assumption of heterogeneity in COVID-19 patient populations, and this assumption can lead to erroneous conclusions. Research Question: Do plasma biomarker profiles reflective of various pathophysiologic pathways provide evidence for heterogeneity in hospitalized patients with COVID-19? Study Design and Methods: This is a secondary analysis of two prospective observational studies of adult patients hospitalized with COVID-19-related respiratory failure in the general ward and ICU of two medical centers and with 44 host response biomarkers available. Parsimonious models were used to allocate and validate ARDS inflammatory subphenotypes. Novel biological subphenotypes were identified using latent profile analysis (LPA) and hierarchical clustering. Heterogeneity of treatment effect for corticosteroids was assessed using an interaction term in a logistic regression model. Results: The cohort consisted of 162 patients admitted to the ICU and 464 patients admitted to the ward. Using the parsimonious models in ICU patients, only 3.1% to 13% of patients were classified as hyperinflammatory subphenotype. Using de novo subphenotyping techniques, neither clustering nor LPA revealed significant evidence for heterogeneity in the ward (P = .11-.13), ICU (P = .23-.88), or combined cohort (P = .05-.88). Adding clinical variables did not alter results in the ICU or combined cohort. Using the combined approach in the ward cohort, indices provided borderline significance for two subphenotypes, and there was good agreement between clustering and LPA (87.9%), but no heterogeneity of treatment effect for corticosteroids was observed between these two classes (P = .198). Interpretation: Systemic inflammatory subphenotypes derived from patients with ARDS did not reflect the variation in severity of COVID-19 in this study. Empirical evidence, derived from cluster analysis or LPA, offers limited support for biological heterogeneity in COVID-19.
UR - https://www.scopus.com/pages/publications/105000638425
U2 - 10.1016/j.chstcc.2024.100062
DO - 10.1016/j.chstcc.2024.100062
M3 - Article
SN - 2949-7884
VL - 2
JO - CHEST Critical Care
JF - CHEST Critical Care
IS - 2
M1 - 100062
ER -
SDG 3 Good Health and Well-being