Philip Dela Cruz, n/a
Resident Physician
UHS SoCal MEC Internal Medicine Residency, United States
Disclosure information not submitted.
Richard Wargowsky, MS
Teaching Assistant
George Washington University School of Medicine and Health Sciences, United States
Disclosure information not submitted.
Justin Kim, ACNP, MSN (he/him/his)
George Washington University Hospital
Disclosure information not submitted.
Kendarius Talton, n/a
Nurse Practioner
George Washington University hospital, United States
Disclosure information not submitted.
.jpg "Katherine Farrar, MS, PA-C photo")
Katherine Farrar, MS, PA-C
Critical Care Physician Assistant
George Washington University
Washington, District of Columbia, United States
Disclosure information not submitted.
Laura Bradley, PA-C
Physician Assistant
George Washington University hospital, United States
Disclosure information not submitted.
Eugene Kim, PA-C
Physician Assistant
George Washington University Hospital, United States
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Obinna Ome Irondi
George Washington University School of Medicine & Health Sciences
Arlington
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Jennifer Park, MSc
Research Coordinator
George Washington University Hospital, United States
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John Lafleur, MD, PHD
Assistant Professor
George Washington University School of Medicine and Health Sciences, United States
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David Yamane, BS, MD
Assistant Professor of Emergency Medicine, Anesthesiology, and Critical Care Medicine
George Washington University Hospital, United States
Disclosure information not submitted.
Timothy McCaffrey, PHD
Professor
George Washington University School of Medicine and Health Sciences, United States
Disclosure information not submitted.
Title: The Role of Whole Blood DEFA1 mRNA as a Biomarker for COVID Severity
Introduction: Accurately predicting disease severity in COVID19+ is challenging. Known biomarkers for inflammation have variable utility answering this dilemma. Several publications indicate elevated neutrophil activity relative to T cells may indicate a severe response to COVID19. Using both microarrays and RNA sequencing, Defensin alpha 1 (DEFA1) was identified as a sensitive biomarker of neutrophil activation. DEFA1 is a known microbicidal and cytotoxic peptide associated with neutrophil granules. Droplet digital polymerase chain reaction (ddPCR) for DEFA1 mRNA, relative to the transcript actin B (ACTB), is proposed as a novel way to quantify host inflammatory responses to COVID19 infection. We sought to determine if DEFA1 levels as measured by ddPCR correlate with clinical severity in COVID19+ patients.
Methods: Whole blood was collected in RNA stabilizing ‘Tempus’ tubes from COVID19+ ICU patients, floor patients incidentally COVID19+, and a healthy COVID19 negative control group from 30 Oct 2020 – 14 Apr 2021. Using BioRad ddPCR, both DEFA1 mRNA levels and COVID19 viral burden were quantified from whole blood.
Results: RNA stabilized whole blood samples were collected from 38 COVID19+ patients (52.6% female, mean age 57.8yo, 60.5% Black). DEFA1 levels were stratified into 5 groups (1=0-5%, 2=6-10%, 3=11-20%, 4=21-50%, 5= >51%) and compared to a binary classification of SARS-CoV2. Average DEFA1 levels were: critical 86.2% (n=24); moderate 62.5% (n=7); incidental 19.7% (n=7); control 5.28% (n=6). DEFA1 levels for the critical and moderate were significantly greater than control (T < 0.01 for both) and significantly higher in the critical vs incidental (T < 0.01). There was a positive correlation (Pearson R = 0.45) between Sequential Organ Failure Assessment (SOFA) scores and DEFA1 levels. Clinical indicators, such as neutrophil count, lymphocyte count, neutrophil/lymphocyte ratio, and lactate had no significant trends in relation to COVID-19 severity.
Conclusions: Our data suggests that DEFA1 levels may help predict severity and risk of organ failure in COVID19+ patients. DEFA1 levels measured by ddPCR may provide a quick novel test to discriminate outcomes, severity and need for ICU admission in COVID19+ patients. Future studies are needed to elucidate DEFA1 and ddPCR’s ultimate role in clinical decision making.