Abstract

Background: SARS-COV2 virus detected in December 2019, and was considered a pandemic in March 2020 by the WHO. Symptoms range from asymptomatic to life threatening ones. Studying cell-cell interactions in patients' blood samples may lead to novel diagnosis and treatment approaches.

Aim: This study aims to analyze single-cell RNA sequencing data to identify differences in cell-cell communications between healthy and COVID patients and differentially expressed T-cells genes that contributed to immune system antiviral activity.

Materials and methods: Single-Cell RNA sequencing data from seven COVID patients and five healthy individuals were collected from (GEO accession GSE155673). Cell types were identified and cell-cell interactions were inferred for each condition (healthy, moderate and severe COVID patients). Additionally, T cells differentially expressed genes between the three conditions were identified and pathways enrichment were performed.

Results: Eight cell types were identified. Percentage of T cells decreased from 32.76% in healthy individuals to 16% in severe COVID cases. Cell-Cell interactions analysis revealed significant alterations among healthy, moderate, and severe conditions such as reduction of overall incoming signaling in T cells of severe cases. Additionally, SN signaling pathway was identified only in COVID cases, which in turn was found to be in IFN-γ reduction in distinct cell types. Pathways enrichment analysis identified IFN-γ signaling to be upregulated in moderate cases, and to be downregulated in severe ones. Protein interacting with IFN-γ also shows downregulation such as IRF1. However, the negative regulator of IFN-γ -SOCS3- was upregulated in COVID patients T cells.

Conclusion: Cell-cell interactions alteration in COVID patients might have resulted in eliciting improper immune response. Not only, did T cells percentage decreased in severe COVID cases, but also T cells overall incoming signaling was decreased. Additionally, cell-cell interaction alteration might have played a significant role in suppressing antiviral response through IFN-γ reduction which might contribute to the observed severity of COVID cases.

School

School of Sciences and Engineering

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Graduation Date

Spring 5-25-2021

Submission Date

5-25-2021

First Advisor

Hassan Azzazy

Committee Member 1

Ahmed Moustafa

Committee Member 2

Mohamed ElHadidi

Extent

80 p.

Document Type

Master's Thesis

Institutional Review Board (IRB) Approval

Not necessary for this item

Additional Files
Supplementary file 1.xlsx (1663 kB)
Supplementary file1
Supplementary file 2.xlsx (2973 kB)
Supplementary file2
Supplementary file 3.xlsx (813 kB)
Supplementary file3
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