508 - Biomarker elevation during COVID-19: Differences between ambulatory and hospitalized individuals

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Presenting Author(s)

Paul W. Blair

Assistant Professor
Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), Henry M. Jackson Foundation for the Advancement of Military Medicine
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

CL

Charlotte Lanteri

Deputy Program Director
Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences
Boyds, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DS

Deborah Striegel

Research Mathematician
Henry M. Jackson Foundation
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Brian Agan

Deputy Science Director, HJF
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
RM

Ryan C. Maves

Fellowship Program Director
Naval Medical Center San Diego, San Diego, CA and Infectious Disease Clinical Research Program, Bethesda, MD
San DIego, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JC

Josh Chenoweth

Research Scientist
Henry M. Jackson Foundation
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DL

Derek Larson

Chief, Fort Belvoir Infectious Disease
Naval Medical Center San Diego
san diego, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
KM

Katrin Mende

Deputy Research Area Director, EIDAR
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
San Antonio, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
RC

Rhonda E. Colombo

Clinical Research Physician
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Madigan Army Medical Center Division of Infectious Diseases
Tacoma, Washington
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
David A. Lindholm

Deputy Clerkship Director; Associate Professor of Medicine
Brooke Army Medical Center
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AG

Anuradha Ganesan

Infectious Disease Physician Walter Reed National Military Medical Center
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA, Walter Reed National Military Medical Center
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SR

Stephanie A. Richard

Epidemiologist
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CC

Chris Colombo

Director of Virtual Health and Telecritical Care
Madigan Army Medical Center
Joint Base Lewis-McChord, Washington
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CM

Cristian Madar

Staff Physician
Tripler Army Medical Center
Tripler Army Medical Center, Hawaii
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
NH

Nikhil Huprikar

Director of Pulmonary/Critical Care Fellowship
Walter Reed National Military Medical Center
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DT

David R. Tribble

Science Director, Infectious Disease Clinical Research Program
Uniformed Services University of the Health Sciences
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JD

John S. Dumler

Chair of Department of Pathology
Uniformed Services University
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Timothy Burgess

Director
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DC

Danielle Clark

Director of the Austere Environments Consortium for Enhanced Sepsis Outcomes (ACESO) program
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background: While the majority of illness due to COVID-19 does not require hospitalization, little has been described about the host inflammatory response in the ambulatory setting. Differences in the levels of inflammatory signaling proteins between outpatient and hospitalized populations could identify key maladaptive immune responses during COVID-19.

Methods: Samples were collected from 76 participants (41% female, mean 46.8 years of age) enrolled at five military treatment facilities between March 20, 2020 and June 17, 2020 in an ongoing prospective COVID-19 cohort. This analysis was restricted to those with positive SARS-CoV-2 (severe acute respiratory syndrome–coronavirus 2) RT-PCR testing and included hospitalized (N=29; 10 requiring an ICU stay) and non-hospitalized (N=43) participants. Severity markers (IL6, D-dimer, procalcitonin, ferritin, ICAM-1, IL5, lipocalin, RAGE, TNFR, VEGFA, IFNγ, IL1β) were measured in plasma (mg/dL) using the Ella immunoassay and natural log transformed. Univariate negative binomial regression was performed to determine relative risk of hospitalization. Using the full marker panel, we performed a Principal Component Analysis (PCA) to determine directions of maximal variance in the data. Pearson’s correlation coefficient was determined between analytes and each axis.

Results: Participants requiring ambulatory-, hospital-, and ICU-level care had samples collected at 44.0 (IQR: 35.0-51.0), 40.0 (13.0-51.0), and 47.5 (21.0-54.0) days, respectively. Higher unadjusted levels of IL6, D-dimer, procalcitonin, or ferritin were each associated with hospitalization (Table 1). The PCA showed a separation along axes between level of care and duration of symptoms (Fig 1). While significant correlations were noted with a number of biomarkers, PC1 most correlated with TNFR1 (r=0.88) and PC2 most correlated with IL6Ra (r=0.95). PC1 axis variation accounted for 36.5% of variance and the PC2 axis accounted for 20.0% of variance.Figure 1. Principal Component Analysis (PCA) of biomarkers by level of care and symptom duration.

Table 1. Inflammation biomarker levels between level of care requirements.

Conclusion: TNFR1 and IL6Ra levels correlated with differences in the proinflammatory states between hospitalized and non-hospitalized individuals including time points late in the course of illness. Further analysis of these preliminary findings is needed to evaluate for differences by stages of illness.