Rombout B.E. van Amstel MD , Erik H.A. Michels MD , Brent Appelman MD , Justin de Brabander MD , Patrick J. Smeele MD , Tom van der Poll MD, PhD , Alexander P.J. Vlaar MD, PhD , Lonneke A. van Vught MD, PhD , Lieuwe D.J. Bos MD, PhD , the Amsterdam UMC COVID-19 Biobank Study Group
{"title":"Biomarker Analysis Provides Evidence for Host Response Homogeneity in Patients With COVID-19","authors":"Rombout B.E. van Amstel MD , Erik H.A. Michels MD , Brent Appelman MD , Justin de Brabander MD , Patrick J. Smeele MD , Tom van der Poll MD, PhD , Alexander P.J. Vlaar MD, PhD , Lonneke A. van Vught MD, PhD , Lieuwe D.J. Bos MD, PhD , the Amsterdam UMC COVID-19 Biobank Study Group","doi":"10.1016/j.chstcc.2024.100062","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Research Question</h3><p>Do plasma biomarker profiles reflective of various pathophysiologic pathways provide evidence for heterogeneity in hospitalized patients with COVID-19?</p></div><div><h3>Study Design and Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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 (<em>P</em> = .11-.13), ICU (<em>P</em> = .23-.88), or combined cohort (<em>P</em> = .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 (<em>P</em> = .198).</p></div><div><h3>Interpretation</h3><p>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.</p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"2 2","pages":"Article 100062"},"PeriodicalIF":0.0000,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949788424000169/pdfft?md5=23f368aa8ea0fa264b1390baa2d98c1c&pid=1-s2.0-S2949788424000169-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CHEST critical care","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949788424000169","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
