Prospecting transcriptional markers in COVID-19
SARS-CoV-2, differential gene expression, alternative splicing, RNA editing.
SARS-CoV-2, the virus causing COVID-19 was first described in Wuhan, China in 2019, from where it quickly spread worldwide, causing the pandemic announced in March 2020. Several studies have found viral mechanisms of immune escape that disrupt the development of the response generated by the innate immune system and delay the response of the adaptive immune system. These mechanisms include the ability of the virus to repress antiviral response caused by interferons (IFNs), and the ability to interfere with splicing processes. Both mechanisms are accomplished with the aid of viral proteins expressed in the host cell and generate a complex response, requiring large-scale analysis to elucidate the consequences of pathogen-host interactions. In this work, modulation of gene expression, alternative splicing patterns and RNA editing were evaluated from the immune cell transcriptome available in public databases. Transcript expression analyses in peripheral blood mononuclear cells (PBMC) from patients with moderate-stage COVID-19 showed little immune system response and enriched terms related to viral replication, operations between set of differentially expressed genes in COVID-19 and dengue showed similar NF-kB-induced inflammatory response, indicating a possible inflammatory response, with diminished antiviral, host-damaging response, in COVID-19. Signature related to IFN response was enriched in genes with differential alternative splicing. CD74 and MX2 genes related to IFN-1 pathways showed differential alternative splicing with loss of function. Expression analysis of circulating monocytes from infected patients in severe state showed decreased IFN-1 response compared to mild cases, correlation with hypoxic state, increased inflammatory response via NF-kB and RNA editing patterns that indicate decreased IFNs response and may help to understand downregulation and infection of this cell type.