The healthy immune system eliminates pathogens and maintains tissue homeostasis through extraordinarily complex networks with feedback systems while avoiding potentially massive tissue destruction. Many parameters influence humoral and cellular vaccine responses, including intrinsic and extrinsic, environmental, and behavioral, nutritional, perinatal and administrative parameters. The relative contributions of persisting antibodies and immune memory as well as the determinants of immune memory induction, to protect against specific diseases are the main parameters of long-term vaccine efficacy. Natural and vaccine-induced immunity and monoclonal antibody immunotherapeutic, may be evaded by SARS-CoV-2 variants. Besides the complications of the production of COVID-19 vaccinations, there is no effective single treatment against COVID-19. However, administration of a combined treatment at different stages of COVID-19 infection may offer some cure assistance. Combination treatment of antiviral drugs and immunomodulatory drugs may reduce inflammation in critical COVID-19 patients with cytokine release syndrome. Molnupiravir, remdesivir and paxlovid are the approved antiviral agents that may reduce the recovery time. In addition, immunomodulatory drugs such as lactoferrin and monoclonal antibodies are used to control inflammatory responses in their respective auto-immune conditions. Therefore, the widespread occurrence of highly transmissible variants like Delta and Omicron indicates that there is still a lot of work to be done in designing efficient vaccines and medicines for COVID-19. In this review, we briefly discussed the immunological response against SARS-CoV-2 and the vaccines approved by the World Health Organization (WHO) for COVID-19, their mechanisms, and side effects. Moreover, we mentioned various treatment trials and strategies for COVID-19.