Innate immune response executes the first line of antiviral defense and is essential to obtain immunity against viruses. Pattern recognition receptors (PRRs), codified by germline DNA, are responsible for recognizing widely common molecular patterns shared by pathogens of a certain group. Single-stranded and double-stranded viral RNAs produced during the replication phase of SARS-CoV-2 are recognized by endosomal TLRs (TLR7 and TLR8 or TLR3, respectively) and cytosolic RIG-I like receptors (RLRs), mainly RIG-I and MDA-5. After PRR engagement, downstream signaling pathways trigger the activation and nuclear translocation of key transcription factors, such as NF-kB, AP-1 and interferon regulatory factors (IRFs), and the ensuing expression of pro-inflammatory and anti-viral cytokines. Among the most relevant cytokines we can find interleukins (IL-1, IL-6 and IL-18), pro-inflammatory TNF-α and TNF-ß, and type I and III IFNs . Consequently, cytokines induce antiviral processes potentiating the innate and adaptive immune responses, limiting CoVs replication capacity and inducing the elimination of the virus cell reservoirs . However, CoVs have developed mechanisms of immune evasion where viral factors inhibit viral recognition by PRR sensing, and cytokine expression and secretion. Individuals with severe COVID-19 have demonstrated remarkably impaired type I IFN values as compared to mild patients , and the interferon-induced overexpression of ACE2 may be involved .