TY - JOUR
T1 - Distinct blood inflammatory biomarker clusters stratify host phenotypes during the middle phase of COVID-19
AU - the EPICC COVID-19 Cohort Study Group
AU - Blair, Paul W.
AU - Brandsma, Joost
AU - Chenoweth, Josh
AU - Richard, Stephanie A.
AU - Epsi, Nusrat J.
AU - Mehta, Rittal
AU - Striegel, Deborah
AU - Clemens, Emily G.
AU - Alharthi, Sultanah
AU - Lindholm, David A.
AU - Maves, Ryan C.
AU - Larson, Derek T.
AU - Mende, Katrin
AU - Colombo, Rhonda E.
AU - Ganesan, Anuradha
AU - Lalani, Tahaniyat
AU - Colombo, Christopher J.
AU - Malloy, Allison A.
AU - Snow, Andrew L.
AU - Schully, Kevin L.
AU - Lanteri, Charlotte
AU - Simons, Mark P.
AU - Dumler, John S.
AU - Tribble, David
AU - Burgess, Timothy
AU - Pollett, Simon
AU - Agan, Brian K.
AU - Clark, Danielle V.
AU - Cowden, J.
AU - Darling, M.
AU - Merritt, T.
AU - Wellington, T.
AU - Rutt, A.
AU - Conlon, C.
AU - Faestel, P.
AU - Mount, C.
AU - Smith, A.
AU - Tant, R.
AU - Warkentien, T.
AU - Berjohn, C.
AU - Utz, G.
AU - Madar, C.
AU - Uyehara, C.
AU - Chung, K.
AU - English, C.
AU - Fox, C.
AU - Grother, M.
AU - Hickey, P.
AU - Laing, E.
AU - Scher, A.
N1 - Funding Information:
S. D. P., M.P.S., T. H. B, and D.R.T. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US Government COVID-19 response. Neither is related to the work presented here. All other authors declare no competing interests.
Funding Information:
The authors wish to also acknowledge all who have contributed to the EPICC COVID-19 study in the Supplementary Information file. EPICC COVID-19 Cohort Study Group: We thank the members of the EPICC COVID-19 Cohort Study Group for their many contributions in conducting the study and ensuring effective protocol operations. The members of this group were all closely involved with the design, implementation, and/or oversight of the study and have met group authorship criteria for this manuscript. The contents of this article are the sole responsibility of the authors and do not necessarily reflect the views, assertions, opinions, or policies of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Uniformed Services University of the Health Sciences (USU), National Institutes of Health or Department of Health and Human Services, Brooke Army Medical Center, Fort Belvoir Community Hospital, Madigan Army Medical Center, Walter Reed National Military Medical Center, Naval Medical Center San Diego, Naval Medical Center Portsmouth, Naval Medical Research Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Defense Health Agency, the Departments of the Air Force, Navy, or Army, the U.S. Department of Defense, the U.S. Government, or any other government or agency. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Some of the authors of this work are military service members or employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. x105 provides that ‘‘Copyright protection under this title is not available for any work of the United States Government.’’ Title 17 U.S.C. x101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties. The investigators have adhered to the policies for protection of human subjects as prescribed in 45 CFR 46. This research has been approved the USU Institutional Review Board in compliance with all applicable federal regulations governing the protection of human subjects.
Funding Information:
This project has been funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Inter-Agency Agreement Y1-AI-5072, the Defense Health Program, U.S. DoD, under award HU0001190002, and the Defense Health Agency, U.S. DoD, under awards HU00012020070 and W911QY-20-9-0006. Biomarker assay reagents and analysis support was provided by JPEO W911QY-20-9-0004 (2020 OTA).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85145080691&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-26965-7
DO - 10.1038/s41598-022-26965-7
M3 - Article
C2 - 36577783
AN - SCOPUS:85145080691
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 22471
ER -