Distinct blood inflammatory biomarker clusters stratify host phenotypes during the middle phase of COVID-19

Author:

Blair Paul W.,Brandsma Joost,Chenoweth Josh,Richard Stephanie A.,Epsi Nusrat J.,Mehta Rittal,Striegel Deborah,Clemens Emily G.,Alharthi Sultanah,Lindholm David A.,Maves Ryan C.,Larson Derek T.,Mende Katrin,Colombo Rhonda E.,Ganesan Anuradha,Lalani Tahaniyat,Colombo Christopher J.,Malloy Allison A.,Snow Andrew L.,Schully Kevin L.,Lanteri Charlotte,Simons Mark P.,Dumler John S.,Tribble David,Burgess Timothy,Pollett Simon,Agan Brian K.,Clark Danielle V.,Cowden J.,Darling M.,Merritt T.,Wellington T.,Rutt A.,Conlon C.,Faestel P.,Mount C.,Smith A.,Tant R.,Warkentien T.,Berjohn C.,Utz G.,Madar C.,Uyehara C.,Chung K.,English C.,Fox C.,Grother M.,Hickey P.,Laing E.,Livezey J.,Parmelee E.,Rozman J.,Sanchez M.,Scher A.,Chao T.,Chapleau R.,Fries A.,Reynolds K.,Hostler D.,Hostler J.,Lago K.,Maldonado C.,Hunter T.,Mody R.,Wayman M.,Huprikar N.,

Abstract

AbstractThe associations between clinical phenotypes of coronavirus disease 2019 (COVID-19) and the host inflammatory response during the transition from peak illness to convalescence are not yet well understood. Blood plasma samples were collected from 129 adult SARS-CoV-2 positive inpatient and outpatient participants between April 2020 and January 2021, in a multi-center prospective cohort study at 8 military hospitals across the United States. Plasma inflammatory protein biomarkers were measured in samples from 15 to 28 days post symptom onset. Topological Data Analysis (TDA) was used to identify patterns of inflammation, and associations with peak severity (outpatient, hospitalized, ICU admission or death), Charlson Comorbidity Index (CCI), and body mass index (BMI) were evaluated using logistic regression. The study population (n = 129, 33.3% female, median 41.3 years of age) included 77 outpatient, 31 inpatient, 16 ICU-level, and 5 fatal cases. Three distinct inflammatory biomarker clusters were identified and were associated with significant differences in peak disease severity (p < 0.001), age (p < 0.001), BMI (p < 0.001), and CCI (p = 0.001). Host-biomarker profiles stratified a heterogeneous population of COVID-19 patients during the transition from peak illness to convalescence, and these distinct inflammatory patterns were associated with comorbid disease and severe illness due to COVID-19.

Funder

Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense

National Institute of Allergy and Infectious Diseases, National Institutes of Health

Defense Health Program, U.S. DoD

Defense Health Agency, U.S. DoD

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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