Frontiers in Immunology (Jul 2021)
High-Density Blood Transcriptomics Reveals Precision Immune Signatures of SARS-CoV-2 Infection in Hospitalized Individuals
- Jeremy W. Prokop,
- Jeremy W. Prokop,
- Nicholas L. Hartog,
- Nicholas L. Hartog,
- Dave Chesla,
- Dave Chesla,
- William Faber,
- Chanise P. Love,
- Rachid Karam,
- Nelly Abualkheir,
- Benjamin Feldmann,
- Li Teng,
- Tamara McBride,
- Mara L. Leimanis,
- Mara L. Leimanis,
- B. Keith English,
- Amanda Holsworth,
- Austin Frisch,
- Jacob Bauss,
- Nathisha Kalpage,
- Aram Derbedrossian,
- Ryan M. Pinti,
- Nicole Hale,
- Joshua Mills,
- Alexandra Eby,
- Elizabeth A. VanSickle,
- Spencer C. Pageau,
- Rama Shankar,
- Rama Shankar,
- Bin Chen,
- Bin Chen,
- Joseph A. Carcillo,
- Dominic Sanfilippo,
- Dominic Sanfilippo,
- Rosemary Olivero,
- Rosemary Olivero,
- Caleb P. Bupp,
- Caleb P. Bupp,
- Surender Rajasekaran,
- Surender Rajasekaran,
- Surender Rajasekaran
Affiliations
- Jeremy W. Prokop
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Jeremy W. Prokop
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
- Nicholas L. Hartog
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Nicholas L. Hartog
- Allergy & Immunology, Spectrum Health, Grand Rapids, MI, United States
- Dave Chesla
- Office of Research, Spectrum Health, Grand Rapids, MI, United States
- Dave Chesla
- Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- William Faber
- Physical Sciences, Grand Rapids Community College, Grand Rapids, MI, United States
- Chanise P. Love
- Office of Research, Spectrum Health, Grand Rapids, MI, United States
- Rachid Karam
- Ambry Genetics, Aliso Viejo, CA, United States
- Nelly Abualkheir
- Ambry Genetics, Aliso Viejo, CA, United States
- Benjamin Feldmann
- Ambry Genetics, Aliso Viejo, CA, United States
- Li Teng
- Ambry Genetics, Aliso Viejo, CA, United States
- Tamara McBride
- Ambry Genetics, Aliso Viejo, CA, United States
- Mara L. Leimanis
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Mara L. Leimanis
- Pediatric Intensive Care Unit, Helen DeVos Children’s Hospital, Grand Rapids, MI, United States
- B. Keith English
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Amanda Holsworth
- Allergy & Immunology, Spectrum Health, Grand Rapids, MI, United States
- Austin Frisch
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Jacob Bauss
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Nathisha Kalpage
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Aram Derbedrossian
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Ryan M. Pinti
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Nicole Hale
- The Department of Chemistry and Biochemistry, Calvin University, Grand Rapids, MI, United States
- Joshua Mills
- 0Department of Biology, Grand Valley State University, Allendale, MI, United States
- Alexandra Eby
- 1Department of Science, Davenport University, Grand Rapids, MI, United States
- Elizabeth A. VanSickle
- Allergy & Immunology, Spectrum Health, Grand Rapids, MI, United States
- Spencer C. Pageau
- Office of Research, Spectrum Health, Grand Rapids, MI, United States
- Rama Shankar
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Rama Shankar
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
- Bin Chen
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Bin Chen
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
- Joseph A. Carcillo
- 2Department of Critical Care Medicine and Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Dominic Sanfilippo
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Dominic Sanfilippo
- Pediatric Intensive Care Unit, Helen DeVos Children’s Hospital, Grand Rapids, MI, United States
- Rosemary Olivero
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Rosemary Olivero
- 3Infectious Disease, Helen DeVos Children’s Hospital, Grand Rapids, MI, United States
- Caleb P. Bupp
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Caleb P. Bupp
- 4Medical Genetics, Spectrum Health Medical Genetics, Grand Rapids, MI, United States
- Surender Rajasekaran
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
- Surender Rajasekaran
- Office of Research, Spectrum Health, Grand Rapids, MI, United States
- Surender Rajasekaran
- Pediatric Intensive Care Unit, Helen DeVos Children’s Hospital, Grand Rapids, MI, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.694243
- Journal volume & issue
-
Vol. 12
Abstract
The immune response to COVID-19 infection is variable. How COVID-19 influences clinical outcomes in hospitalized patients needs to be understood through readily obtainable biological materials, such as blood. We hypothesized that a high-density analysis of host (and pathogen) blood RNA in hospitalized patients with SARS-CoV-2 would provide mechanistic insights into the heterogeneity of response amongst COVID-19 patients when combined with advanced multidimensional bioinformatics for RNA. We enrolled 36 hospitalized COVID-19 patients (11 died) and 15 controls, collecting 74 blood PAXgene RNA tubes at multiple timepoints, one early and in 23 patients after treatment with various therapies. Total RNAseq was performed at high-density, with >160 million paired-end, 150 base pair reads per sample, representing the most sequenced bases per sample for any publicly deposited blood PAXgene tube study. There are 770 genes significantly altered in the blood of COVID-19 patients associated with antiviral defense, mitotic cell cycle, type I interferon signaling, and severe viral infections. Immune genes activated include those associated with neutrophil mechanisms, secretory granules, and neutrophil extracellular traps (NETs), along with decreased gene expression in lymphocytes and clonal expansion of the acquired immune response. Therapies such as convalescent serum and dexamethasone reduced many of the blood expression signatures of COVID-19. Severely ill or deceased patients are marked by various secondary infections, unique gene patterns, dysregulated innate response, and peripheral organ damage not otherwise found in the cohort. High-density transcriptomic data offers shared gene expression signatures, providing unique insights into the immune system and individualized signatures of patients that could be used to understand the patient’s clinical condition. Whole blood transcriptomics provides patient-level insights for immune activation, immune repertoire, and secondary infections that can further guide precision treatment.
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