Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the most recent global health threat, is spreading throughout the world with worrisome speed, and the current wave of coronavirus disease 2019 (COVID-19) seems to have no mercy. While this mysterious virus challenges our ability to control viral infections, our opportunities to control the COVID-19 pandemic are gradually fading. Currently, pandemic management relies on preventive interventions. Although prevention is a good strategy to mitigate SARS-CoV-2 transmission, it still cannot be considered an absolute solution to eliminate this pandemic. Currently, developing a potent immunity against this viral infection seems to be the most promising strategy to drive down this ongoing global tragedy. However, with the emergence of new challenges in the context of immune responses to COVID-19, the road to control this devastating pandemic seems bumpier; thus, it is pivotal to characterize the dynamics of host immune responses to COVID-19, in order to develop efficient prophylactic and therapeutic tools. This begs the question of whether the effector mechanisms of the immune system are indeed potent or a possible contributing factor to developing more severe and lethal forms of COVID-19. In this review, the possible role of the immunopathologic phenomena including antibody-dependent enhancement, cytokine storm, and original antigenic sin in severity and mortality of COVID-19 will be discussed.