Reinfection with SARS-CoV-2 is not frequent yet the incidence rate of it is increasing globally owing to the slow emergence of drift variants that pose a perpetual threat to vaccination strategies and have a greater propensity for disease reoccurrence. Long-term protection against SARS-CoV-2 reinfection relies on the induction of the innate as well as the adaptive immune response endowed with immune memory. However, a multitude of factors including the selection pressure, the waning immunity against SARS-CoV-2 over the first year after infection possibly favors evolution of more infectious immune escape variants, amplifying the risk of reinfection. Additionally, the correlates of immune protection, the novel SARS-CoV-2 variants of concern (VOC), the durability of the adaptive and mucosal immunity remain major challenges for the development of therapeutic and prophylactic interventions. Interestingly, a recent body of evidence indicated that the gastrointestinal (GI) tract is another important target organ for SARS-CoV-2 besides the respiratory system, potentially increasing the likelihood of reinfection by impacting the microbiome and the immune response via the gut-lung axis. In this review, we summarized the latest development in SARS-CoV-2 reinfection, and explored the untapped potential of trained immunity. We also highlighted the immune memory kinetics of the humoral and cell-mediated immune response, genetic drift of the emerging viral variants, and discussed the current challenges in vaccine development. Understanding the dynamics and the quality of immune response by unlocking the power of the innate, humoral and cell-mediated immunity during SARS-CoV-2 reinfection would open newer avenues for drug discovery and vaccine designs.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 93 million cases and 2 million deaths in the world. SARS-CoV-2 respiratory tract infection and its main clinical manifestations such as cough and shortness of breath are well known to the scientific community. However, a growing number of studies have reported SARS-CoV-2-related gastrointestinal involvement based on clinical manifestations, such as diarrhea, nausea, vomiting, and abdominal pain as well as on the pathophysiological mechanisms associated with coronavirus disease 2019. Furthermore, current evidence suggests SARS-CoV-2 transmission via the fecal-oral route and aerosol dissemination. Moreover, studies have shown a high risk of contamination through hospital surfaces and personal fomites. Indeed, viable SARS-CoV-2 specimens can be obtained from aerosols, which raises the possibility of transmission through aerosolized viral particles from feces. Therefore, the infection by SARS-CoV-2 via fecal-oral route or aerosolized particles should be considered. In addition, a possible viral spread to sources of drinking water, sewage, and rivers as well as the possible risk of viral transmission in shared toilets become a major public health concern, especially in the least developed countries. Since authors have emphasized the presence of viral RNA and even viable SARS-CoV-2 in human feces, studies on the possible fecal-oral coronavirus disease 2019 transmission become essential to understand better the dynamics of its transmission and, then, to reinforce preventive measures against this infection, leading to a more satisfactory control of the incidence of the infection.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes the most significant global public health challenge in a century. It has reignited research interest in coronavirus. While little information is available, research is currently in progress to comprehensively understand the general biology and immune response mechanism against SARS-CoV-2. The spike proteins (S protein) of SARS-CoV-2 perform a crucial function in viral infection establishment. ACE2 and TMPRSS2 play a pivotal role in viral entry. Upon viral entry, the released pro-inflammatory proteins (cytokines and chemokines) cause the migration of the T cells, monocytes, and macrophages to the infection site. IFNϒ released by T cells initiates a loop of pro-inflammatory feedback. The inflammatory state may further enhance with an increase in immune dysfunction responsible for the infection's progression. A treatment approach that prevents ACE2-mediated viral entry and reduces inflammatory response is a crucial therapeutic intervention strategy, and nanomaterials and their conjugates are promising candidates. Nanoparticles can inhibit viral entry and replication. Nanomaterials have also found application in targeted drug delivery and also in developing a vaccine against SARS-CoV-2. Here, we briefly summarize the origin, transmission, and clinical features of SARS-CoV-2. We then discussed the immune response mechanisms of SARS-CoV-2. Finally, we further discussed nanotechnology's potentials as an intervention strategy against SARS-CoV-2 infection. All these understandings will be crucial in developing therapeutic strategies against SARS-CoV-2.