Summary and Future perspectives:
The novel corona virus, SARS-CoV-2, is one of the most challenging crises that faced the whole world since the 1918 Influenza outbreak unveiling the hidden weaknesses of the health care systems globally and urging the need for efficient and safe vaccines and therapies development. Luckily, vaccine research has advanced dramatically over the last period, with the creation of multiple types of RNA and DNA vaccines, approved viral vector vaccines, recombinant peptides in addition to cell culture based immunotherapies(110) . Based on the high similarity between SARS-CoV-2 and SARS, the identification of S protein, present in both viruses and responsible for virus binding to the host cell membrane and its internalization into the cell has been facilitated and proposed as the main target for many vaccines under trials. This will help in quick production of neutralizing antibodies that bind to the S protein and hence prevent the infection process. Nevertheless, although many S protein targeting vaccines have been developed already aiming to protect against SARS and MERS, most of them did not give the desirable results when tested in animal models or caused severe harmful effects as lung injury or multiorgan failure(111),(112).  In addition, it is not well-known whether the infection with this virus involves lifelong immunity nor the possibility of re-infections which urge researchers all over the world to continue their research on this topic in order to explore the exact pathophysiology of the virus and to develop a highly effective vaccine and treatment.
However, the specific immune signaling pathways stimulated by SARS-CoV-2 are still to be well identified as this may ensure a great hope in revealing the reliable and significant biological markers to be targeted in vaccines and immunotherapies in order to block the cytokine storm occurring in most of the severe cases. Moreover, since it is known that the innate immunity stimulates many signaling pathways, it would be more promising to target various signaling pathways simultaneously during the course of treatment which should include a combination of specific cytokine blockers, corticosteroids as well as S1PR1 agonists instead of administering only one drug as this may enhance the chance of recovery especially in advanced cases. Therefore, more studies are needed to evaluate if this combination of drugs could protect the patients against the progression of lung damage and multi organ failure compared with single target drug regime plans.
Finally, all the above-mentioned issues illustrate some of the main holes in our understanding of COVID-19 physiological implications, fundamental immune signaling mechanisms, and effective vaccines development strategies that prospective studies desperately need to tackle.