Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation

Sean E Gill; Claudia C Dos Santos; David B O'Gorman; David E Carter; Eric K Patterson; Marat Slessarev; Claudio Martin; Mark Daley; Michael R Miller; Gediminas Cepinskas; Douglas D Fraser; Lawson COVID19 Study Team

doi:10.1186/s40635-020-00361-9

Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation

Intensive Care Med Exp. 2020 Dec 11;8(1):75. doi: 10.1186/s40635-020-00361-9.

Authors

Sean E Gill^{1

2

3

4}, Claudia C Dos Santos⁵, David B O'Gorman^{6

7}, David E Carter⁸, Eric K Patterson⁶, Marat Slessarev^{6

9}, Claudio Martin^{6

9}, Mark Daley^{6

10}, Michael R Miller^{6

11}, Gediminas Cepinskas^{6

12}, Douglas D Fraser^{13

14

15

16}; Lawson COVID19 Study Team

Collaborators

Lawson COVID19 Study Team:
Robert Arntfield, Ian Ball, Gordon Barkwell, Tracey Bentall, Karen Bosma, Saoirse Cameron, Eileen Campbell, Carolina Gillio-Meina, Robert Hegele, Natalya Odoardi, Ram Singh, Kelly Summers, Sue Tereschyn

Affiliations

¹ Lawson Health Research Institute, London, ON, Canada. sgill8@uwo.ca.
² Physiology and Pharmacology, Western University, London, ON, Canada. sgill8@uwo.ca.
³ Medicine, Western University, London, ON, Canada. sgill8@uwo.ca.
⁴ Victoria Research Labs, Room A6-134, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. sgill8@uwo.ca.
⁵ Interdepartmental Division of Critical Care Medicine and Keenan Center for Biomedical Research of St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
⁶ Lawson Health Research Institute, London, ON, Canada.
⁷ Biochemistry, Western University, London, ON, Canada.
⁸ London Regional Genomics Centre, Western University, London, ON, Canada.
⁹ Medicine, Western University, London, ON, Canada.
¹⁰ Computer Science, Western University, London, ON, Canada.
¹¹ Pediatrics, Western University, London, ON, Canada.
¹² Medical Biophysics, Western University, London, ON, Canada.
¹³ Lawson Health Research Institute, London, ON, Canada. douglas.fraser@lhsc.on.ca.
¹⁴ Physiology and Pharmacology, Western University, London, ON, Canada. douglas.fraser@lhsc.on.ca.
¹⁵ Pediatrics, Western University, London, ON, Canada. douglas.fraser@lhsc.on.ca.
¹⁶ London Health Sciences Centre, Room C2-C82, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. douglas.fraser@lhsc.on.ca.

Abstract

Background: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.

Results: We enrolled seven COVID19 + (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 + patients were more likely to suffer bilateral pneumonia. The mortality rate for this cohort of COVID19 + ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 + ICU patients were: (i) a robust overrepresentation of interferon-related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor/interleukin 6 signalling.

Conclusions: Our findings demonstrate that critically ill COVID19 + patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.

Keywords: COVID19; Leukocyte transcriptome; RNAseq.