Human infection by coronaviruses has become a significant health problem. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells using its large viral Spike protein which is activated by serine protease TMPRSS2. Following binding to its receptor, angiotensin-converting enzyme 2 (ACE2), the virus enters the cell. ACE2 is down-regulated which results in further angiotensin 2 accumulation. Activation of the angiotensin pathway system causes lung injury in response to the virus. A variety of signaling events occur in the lung epithelial and immune cells following infections by Covid-19 and other viruses. These include chemokine and cytokine induced processes, signaling pathways and transcription factors. SARS-2 (Covid-19) triggers the hosts innate immune system through the type I interferon system resulting in the activation of ISRE and IFN-beta sensitive promoter elements. Understanding the immune response to viral infection and the cascade of events that leads to tissue damage and death is important to developing diagnostic methods and new treatments.