Meta-analysis of SARS-coV-2 affected lung biopsies and PBMCs reveal enrichment of various pathways pertaining to immune response
SARS-coV-2 infection caused a massive surge in inflammatory response, cytokine production and cytokine-mediated signaling. There was a substantial up-regulation of immune response including the processes of hematopoietic development and lymphocyte activation (Figure 1A,3A,3B). Activation of viral life cycle and anti-viral interferon signaling was observed in infected lungs and A549 cells (Figure 1B, 5). Over-representation of pathways including NOD-like receptor signaling, MAPK cascade, Measles and Influenza-A were seen in the infected lung as identified by gene set enrichment analysis (Figure 1A). Targets of transcription factors, ISRE and IRF were upregulated in SARS-coV-2 affected lungs similar to up-regulation observed in the PBMC of SLE patients (Figure 1B, 1C). Enrichr analysis revealed that the genes up-regulated in SARS-coV-2 lung were down-regulated when SYK was knocked down or inhibited (Figure 1D). Expression to kinase (X2K) analysis showed the possible perturbation of various MAP kinases, ABL1 and JNK1 (Figure 1E,1F). Human phenotype enrichment analysis shows thrombocytopenia, poor wound healing, abnormality of lymphatic system, serositis and abnormal anticoagulant pathways in SARS-coV-2 infected lungs (Figure S1).