Immune characterization and profiles of SARS-CoV-2 infected patients reveals potential host therapeutic targets and SARS-CoV-2 oncogenesis mechanism

Abstract

The spread of SARS-CoV-2 and the increasing mortality rates of COVID-19 create an urgent need for treatments, which are currently lacking. Although vaccines have been approved by the FDA for emergency use in the U.S., patients will continue to require pharmacologic intervention to reduce morbidity and mortality as vaccine availability remains limited. The rise of new variants makes the development of therapeutic strategies even more crucial to combat the current pandemic and future outbreaks. Evidence from several studies suggests the host immune response to SARS-CoV-2 infection plays a critical role in disease pathogenesis. Consequently, host immune factors are becoming more recognized as potential biomarkers and therapeutic targets for COVID-19. To develop therapeutic strategies to combat current and future coronavirus outbreaks, understanding how the coronavirus hijacks the host immune system during and after the infection is crucial. In this study, we investigated immunological patterns or characteristics of the host immune response to SARS-CoV-2 infection that may contribute to the disease severity of COVID-19 patients. We analyzed large bulk RNASeq and single cell RNAseq data from COVID-19 patient samples to immunoprofile differentially expressed gene sets and analyzed pathways to identify human host protein targets. We observed an immunological profile of severe COVID-19 patients characterized by upregulated cytokines, interferon-induced proteins, and pronounced T cell lymphopenia, supporting findings by previous studies. We identified a number of host immune targets including PERK, PKR, TNF, NF-kB, and other key genes that modulate the significant pathways and genes identified in COVID-19 patients. Finally, we identified genes modulated by COVID-19 infection that are implicated in oncogenesis, including E2F7 and RB1, suggesting a mechanism by which cancer may arise in patients infected with SARS-CoV2. Further clinical investigation of these targets may lead to bonafide therapeutic strategies to treat the current COVID-19 pandemic and protect against future outbreaks and viral escape variants.

In vivo single-cell profiling of lncRNAs during Ebola virus infection

“…S6E). Consistent with previous studies regarding immune response upon infection, LINC00877 (Razooky et al 2017;Policard et al 2021) was downregulated, and SNHG6 upregulated (Zhao et al 2016;Waickman et al 2019). Interestingly, the most transcriptionally repressed lncRNA was the nuclear enriched abundant transcript 1 (NEAT1) (Figure 3C, H).…”

A path-based analysis of infected cell line and COVID-19 patient transcriptome reveals novel potential targets and drugs against SARS-CoV-2

“…As shown in Fig. 5A , pathways enriched among the frequent central genes in activated TopNets are predominantly related to cell cycle, which is an expected response to infection by the host immune system ( 55 ), as well as potentially linking SC2 infection with cancer ( 56 , 57 ). Previous studies have observed that cancer patients are more vulnerable to SC2 infection leading to adverse outcomes, likely due to compromised immune system ( 58 ).…”

ScRNA-Seq Reveals T Cell Immunity in COVID-19 Patients and Implications for Immunotherapy

“…CD8 + T cells CD8 + T cells were markedly reduced but CD8 + /CD4 + T cell ratio was higher in COVID-19-infected patients [25,[56][57][58], which was also evidenced by clonally-expanded CD8 + T cells in the blood and bronchoalveolar lavage using scRNA-seq analysis [42,59,60]. CD8 + T cells highly expressed activation markers, such as CD69, TNFAIP3 and HLA class II genes (HLA-DRA ,HLA-DRB1 , and HLA-DRB5 ) [30,34] (Figure 1).…”