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Immune Transcriptomes from Hospitalized Patients Infected with the SARS-CoV-2 Variants B.1.1.7 and B.1.1.7 Carrying the E484K Escape Mutation

33 Pages Posted: 14 Jun 2021 Publication Status: Review Complete

See all articles by Ludwig Knabl

Ludwig Knabl

TyrolPath

Knabl Sr. Ludwig

Krankenhaus St. Vinzenz

Hye Kyung Lee

National Institutes of Health - National Institute of Diabetes, Digestive and Kidney Diseases

Manuel Wieser

TyrolPath

Anna Mur

Krankenhaus Kufstein - Division of Internal Medicin

August Zabernigg

Krankenhaus Kufstein - Division of Internal Medicin

Jana Schumacher

Krankenhaus St. Johann - Division of Internal Medicine

Norbert Kaiser

Krankenhaus St. Johann - Division of Internal Medicine

Priscilla A. Furth

Georgetown University - Departments of Oncology & Medicine

Lothar Hennighausen

Government of the United States of America - Laboratory of Genetics and Physiology

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Abstract

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. B.1.1.7 (VOC-202012/01) has become the predominant variant in many countries and a new lineage (VOC-202102/02) harboring the E484K escape mutation in the B.1.1.7 background emerged in February 2021. This variant is of concern due to reduced neutralizing activity by vaccine-elicited antibodies. However, it is not known whether this single amino acid change leads to an altered immune response. Here, we investigate differences in the immune transcriptome in hospitalized patients infected with either B.1.1.7 (n=28) or B.1.1.7+E484K (n=12). RNA-seq conducted on PBMCs isolated within five days after the onset of COVID symptoms demonstrated elevated activation of specific immune pathways, including JAK-STAT signaling, in B.1.1.7+E484K patients as compared to B.1.1.7. Longitudinal transcriptome studies demonstrated a delayed dampening of interferon-activated pathways in B.1.1.7+E484K patients. Prior vaccination with BNT162b vaccine (n=8 one dose; n=1 two doses) reduced the transcriptome inflammatory response to B.1.1.7+E484K infection relative to unvaccinated patients. Lastly, the immune transcriptome of patients infected with additional variants (B.1.258, B.1.1.163 and B.1.7.7) displayed a reduced activation compared to patients infected with B.1.1.7. Acquisition of the E484K substitution in the B.1.1.7 background elicits an altered immune response, which could impact disease progression.

Funding: This work was supported by the Intramural Research Programs (IRPs) of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov).

Declaration of Interest: The authors declare no competing financial interests.

Ethical Approval: This study was approved by the Institutional Review Board (IRB) of the Office of Research Oversight / Regulatory Affairs, Medical University of Innsbruck, Austria (EC numbers:
1064/2021).

Suggested Citation

Knabl, Ludwig and Ludwig, Knabl Sr. and Lee, Hye Kyung and Wieser, Manuel and Mur, Anna and Zabernigg, August and Schumacher, Jana and Kaiser, Norbert and Furth, Priscilla A. and Hennighausen, Lothar, Immune Transcriptomes from Hospitalized Patients Infected with the SARS-CoV-2 Variants B.1.1.7 and B.1.1.7 Carrying the E484K Escape Mutation. Available at SSRN: https://ssrn.com/abstract=3866833 or http://dx.doi.org/10.2139/ssrn.3866833
This version of the paper has not been formally peer reviewed.

Ludwig Knabl

TyrolPath ( email )

Zams
Austria

Knabl Sr. Ludwig

Krankenhaus St. Vinzenz ( email )

Zams
Austria

Hye Kyung Lee

National Institutes of Health - National Institute of Diabetes, Digestive and Kidney Diseases ( email )

United States

Manuel Wieser

TyrolPath ( email )

Zams
Austria

Anna Mur

Krankenhaus Kufstein - Division of Internal Medicin ( email )

Kufstein
Austria

August Zabernigg

Krankenhaus Kufstein - Division of Internal Medicin ( email )

Kufstein
Austria

Jana Schumacher

Krankenhaus St. Johann - Division of Internal Medicine ( email )

St. Johann
Austria

Norbert Kaiser

Krankenhaus St. Johann - Division of Internal Medicine ( email )

St. Johann
Austria

Priscilla A. Furth

Georgetown University - Departments of Oncology & Medicine ( email )

Washington, DC
United States

Lothar Hennighausen (Contact Author)

Government of the United States of America - Laboratory of Genetics and Physiology ( email )

Bethesda, MD 20892
United States