The immune response is vital for the control and resolution of CoV infections, while it can also lead to immunopathogenesis, associated with the immune response out of control. The S proteins of Coronavirus binds to the host cells by ACE2, fusing to the membrane and release the viral RNA. The viral RNAs, as pathogen-associated molecular patterns (PAMPs), are detected by the pattern recognition receptors (PRRs). Usually, Toll-like receptor (TLR) 3, TLR7, TLR8, and TLR9 sense viral RNA and DNA in the endosome [60, 61]. The viral RNA receptor retinoic-acid inducible gene I (RIG-I) [62], cytosolic receptor melanoma differentiation-associated gene 5 (MDA5) and nucleotidyltransferase cyclic GMP-AMP synthase (cGAS) [63] are responsible for the recognition of viral RNA and DNA in the cytoplasm. These complex signalling recruit adaptors, including TIR-domain-containing adaptor protein including IFN-β (TRIF), mitochondrial antiviral-signalling protein (MAVS) [64] and stimulator of interferon genes protein (STING) [65] to trigger downstream cascades molecules, involving adaptor molecule MyD88 and lead to the activation of the transcription factor nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) and the production of type I Interferons (IFN-α /β) and a series of pro-inflammatory cytokines [66]. Hence, virus-cell interactions produce a diverse set of immune mediators against the invading virus [67]. Innate immunity is needed in a precise regulation to eliminate the virus, otherwise will result in immunopathology. A few plasma cytokines and chemokines were observed ascended in COVID-19 patients, including IL-1, IL-2, IL-4, IL-7, IL-10, IL-12, IL-13, IL-17, GCSF, macrophage colony-stimulating factor (MCSF), IP-10, MCP-1, MIP-1α, hepatocyte growth factor (HGF), IFN-γ and TNF-α [48, 68, 69]. Of note, an anatomy report of COVID-19 pneumonia corpse [70] indicated that COVID-19 caused an inflammatory response in the lower airway and led to lung injury. Collectively, the virus particles invade the respiratory mucosa firstly and infect other cells, triggering a series of immune responses and the production of cytokine storm in the body, which may be associated with the critical condition of COVID-19 patients.