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

the EPICC COVID-19 Cohort Study Group, Paul W. Blair*, Joost Brandsma, Josh Chenoweth, Stephanie A. Richard, Nusrat J. Epsi, Rittal Mehta, Deborah Striegel, Emily G. Clemens, Sultanah Alharthi, David A. Lindholm, Ryan C. Maves, Derek T. Larson, Katrin Mende, Rhonda E. Colombo, Anuradha Ganesan, Tahaniyat Lalani, Christopher J. Colombo, Allison A. Malloy, Andrew L. SnowKevin L. Schully, Charlotte Lanteri, Mark P. Simons, John S. Dumler, David Tribble, Timothy Burgess, Simon Pollett, Brian K. Agan, Danielle V. Clark, J. Cowden, M. Darling, T. Merritt, T. Wellington, A. Rutt, C. Conlon, P. Faestel, C. Mount, A. Smith, R. Tant, T. Warkentien, C. Berjohn, G. Utz, C. Madar, C. Uyehara, K. Chung, C. English, C. Fox, M. Grother, P. Hickey, E. Laing, A. Scher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The 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.

Original languageEnglish
Article number22471
JournalScientific Reports
Issue number1
StatePublished - Dec 2022
Externally publishedYes


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