521 - Similarities and Differences in Transcriptomic Host Response between SARS-CoV-2 and Other Viral Infections

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Presenting Author(s)

Simone A. Thair

Senior Computational Biologist
Inflammatix, Inc.
Burlingame, California
Disclosure: Inflammatix, Inc. (Employee, Shareholder)

Co-Author(s)

YH

Yudong He

Vice President
Inflammatix
Burlingame, California
Disclosure: Inflammatix Inc. (Employee)
YH

Yehudit Hasin-Brumshtein

Computational Biologist
Inflammatix
Burlingame, California
Disclosure: Inflammatix (Employee, Shareholder)
SS

Suraj Sakaram

Suraj Sakaram
Inflammatix, Inc.
San Bruno, California
Disclosure: Inflammatix (Employee, Other Financial or Material Support, stock options)
RP

Rushika R. Pandya

Computational Biologist
Inflammatix Inc.
Burlingame, California
Disclosure: Inflammatix Inc. (Employee, Shareholder)
JT

Jiaying Toh

Graduate Student
Stanford University
Stanford, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DR

David C. Rawling

Director
Inflammatix
Burlingame, California
Disclosure: Inflammatix Inc. (Employee, Shareholder)
MR

Melissa Remmel

Staff Scientist
Inflammatix
Burlingame, CA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SC

Sabrina Coyle

Research Associate II
Inflammatix, Inc.
Burlingame, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
GD

George Dalekos

MD, PROFESSOR OF MEDICINE HEAD OF THE DEPARTMENT OF MEDICINE
Department of Internal Medicine, University of Thessaly, Larissa General Hospital, Greece
Larissa, Thessaloniki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
IK

Ioannis Koutsodimitropoulos

Intensive Care Specialist
Consultant
Nea Smyrni, Attiki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
GV

Glykeria Vlachogianni

ICU DIRECTOR
Intensive Care Unit, Aghios Dimitrios Thessaloniki General Hospital, Greece
Kordelio-Evosmos, Thessaloniki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
EG

Eleni Gkeka

MD
7. Intensive Care Unit, AHEPA Thessaloniki General Hospital, Greece
Kordelio-Evosmos, Thessaloniki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
EK

Eleni Karakike

PhD(c), 4th Department of Internal Medicine, National and Kapodistrian University of Athens
4th Department of Internal Medicine, ATTIKON University Hospital
Athens, Attiki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
GD

Georgia Damoraki

Systems Biologist
National Expertise Center of Greece in Autoimmune Liver Diseases
Athens, Attiki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
NA

Nikolaos Antonakos

MD, PhD, Internal Medicine specialist
4th Department of Internal Medicine, ATTIKON University Hospital
Athens, Attiki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
PK

Purvesh Khatri

ASsociate Professor
Stanford University
Stanford, California
Disclosure: Inflammatix Inc. (Shareholder)
EG

Evangelos J. Giamarellos-Bourboulis

Professor of Internal Medicine, Director: Master (MSc) Program of Infectious Diseases
National and Kapodistrian University of Athens, Medical School
Athens, Attiki, Greece
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
TS

Timothy Sweeney

CEO
Inflammatix, Inc
Burlingame, California
Disclosure: Inflammatix, Inc. (Employee, Shareholder)

Background: COVID-19 is a pandemic caused by the SARS-CoV-2 virus that shares and differs in clinical characteristics of known viral infections.

Methods: We obtained RNAseq profiles of 62 prospectively enrolled COVID-19 patients and 24 healthy controls (HC). We collected 23 independent studies profiling 1,855 blood samples from patients covering six viruses (influenza, RSV, HRV, Ebola, Dengue and SARS-CoV-1). We studied host whole-blood transcriptomic responses in COVID-19 compared to non-COVID-19 viral infections to understand similarities and differences in host response. Gene signature threshold was absolute effect size ≥1 , FDR ≤ 0.05%.

Results: Differential gene expression of COVID-19 vs HC are highly correlated with non-COVID-19 vs HC (r=0.74, p< 0.001). We discovered two gene signatures: COVID-19 vs HC (2002 genes) (COVIDsig) and non-COVID-19 vs HC (635 genes) (nonCOVIDsig). Pathway analysis of over-expressed signature genes in COVIDsig or nonCOVIDsig identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection and cytokine production. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and activation (Fig1).
Intersecting the two gene signatures found two genes significantly oppositely regulated (ACO1, ATL3). We derived a third gene signature using COCONUT to compare COVID-19 to non-COVID-19 viral infections (416 genes) (Fig2). Pathway analysis did not result in significant enrichment, suggesting identification of novel biology (Fig1).
Statistical deconvolution of bulk transcriptomic data found M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells and total B cells changed in the same direction across COVID-19 and non-COVID-19 infections. Cell types that increased in COVID-19 relative to non-COVID-19 were CD56^bright NK cells, M2 macrophages and total NK cells. Those that decreased in non-COVID-19 relative to COVID-19 were CD56^dim NK cells & memory B cells and eosinophils (Fig3).Figure 1

Figure 2

Figure 3

Conclusion: The concordant and discordant responses mapped here provide a window to explore the pathophysiology of COVID-19 vs other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2.