Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging RNA virus causing COVID-19 disease, across the globe. SARS-CoV-2 infected patients may exhibit acute respiratory distress syndrome which can be compounded by endemic respiratory viruses and thus highlighting the need to understand the genetic bases of clinical outcome under multiple respiratory infections. In this study, 42 individual datasets and a multi-parametric based selected list of over 12,000 genes against five medically important respiratory viruses (SARS-CoV-2, SARS-CoV-1, influenza A, respiratory syncytial virus (RSV) and rhinovirus were collected and analysed in an attempt to understand differentially regulated gene patterns and to cast genetic markers of individual and multiple co-infections. While a certain cohort of virus-specific genes were regulated (negatively and positively), notably results revealed a greatest correlation among genes regulation by SARS-CoV-2 and RSV. Furthermore, out of analysed genes, the MAP2K5 and NFKBIL1 were specifically and highly upregulated in SARS-CoV-2 infection both in vivo or in vitro. The most conserved genetic signature was JAK2 gene as well as the constitutively downregulated ZNF219 gene. In contrast, several genes including GPBAR1 and SC5DL were specifically downregulated in SARS-CoV-2 datasets. Finally, we catalogued a set of genes that were conserved or differentially regulated across studied respiratory viruses. These finding provide foundational and genome-wide data to gauge the markers of respiratory viral infections individually and under co-infection. This work compares the virogenomic signatures among human respiratory viruses and provides valid targets for potential antiviral therapy.