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 E2F transcription factors and RB1, suggesting a mechanism by which SARS-CoV-2 infection may contribute to oncogenesis. 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.

Deciphering the Relationship between SARS-CoV-2 and Cancer

“…Despite the controversial debate about the oncogenic (or oncolytic) potential of SARS-CoV-2, several genes with a role in oncogenesis have been found regulated upon its infection, such as those corresponding to E2F transcription factors and pRB, thus suggesting a putative mechanism for SARS-CoV-2 in contributing to oncogenesis through the potential inhibition of oncosuppressors [84]. Interactomics studies were pivotal to obtaining such mechanistic insights [85].…”

Ofeleein i mi Vlaptin—Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic

“…On the other hand, mutations of these repair genes seem to drive oncogenesis [38]. In this respect, certain identified genes, including E2F transcription factors and retinoblastoma tumor-suppressor gene (RB1), modulated by COVID-19 infection, appear to be involved in SARS-CoV-2-related carcinogenesis [39]; genetic variants of IL12RB1 confer genetic susceptibility to SARS-CoV-2 infection [40]; and mutations to RB1 and/or components regulating the cyclin dependent kinase-RB-E2F signaling pathway have been recognized in almost every human cancer [41]. In this setting, mutations in genes (hMSHS2, hMLS1, hPMS1, hPMS2) that also control the DNA mismatch repair process have been involved in oncogenesis.…”

SARS-CoV-2 and cancer: the intriguing and informative cross-talk

“…The question of the potential oncogenic role of SARS-COV-2 remains unclear and will only be answered over time. Policard et al (2021) identified genes modulated by COVID-19 infection implicated in oncogenesis, including E2F transcription factors and RB1; this finding suggests a mechanism by which SARS-CoV-2 infection may contribute to oncogenesis [33] . Such observations has not yet been validated in the clinical setting.…”