Neutrophilia and T-cell lymphopenia manifest as an increased neutrophil to lymphocyte ratio. regarding the development of highly effective vaccines and cutting-edge research on novel therapies. We hope that this review furthers the conversations held by scientists and informs the aims of future research projects, which will potentially further our understanding of COVID-19 and its immune pathogenesis. endocytosis (1). The distribution of ACE2 throughout the body dictates SARS-CoV-2 infective tropism. In the respiratory zone of the airways, type II pneumocytes mainly express ACE2, hence constituting the primary target of SARS-CoV-2 in the alveoli (4). A study revealed a decreasing gradient of ACE2 expression from TAS-103 the upper to the lower respiratory tract with a corresponding decline in SARS-CoV-2 viral load. The question in response is how SARS-CoV-2 gets transmitted from the upper to the lower airways? The same study highlighted aspiration-mediated viral seeding of the lower respiratory tract as a potential mechanism, which leads to infection TAS-103 of type II pneumocytes, alveolar macrophages, and endothelial cells expressing ACE2 (5). Cardiac, kidney, gastrointestinal, bile duct, and testicular cells also express ACE2, rendering them susceptible to infection and cytopathic effects (6). Moreover, SARS-CoV-2 RNA and proteins have been detected in the brain, raising suspicion of neurotropism (7) manifesting clinically as anosmia or/and ageusia, which indeed are central features of COVID-19 infection. In addition, demonstration of SARS-CoV-2 elements in the small bowel after clinical recovery suggests that SARS-CoV-2 persists in the gastrointestinal tract, even after recovery. Stool shedding of SARS-CoV-2 occurs, raising concern for potential fecal-oral transmission (6). Although not definitively proven yet, such possible routes of SARS-CoV-2 acquisition should TAS-103 be considered and eliminated in hospital environments to prevent nosocomial infection. Although SARS-CoV-2 infection is less severe than the original SARS-CoV and Middle East Respiratory Syndrome (MERS)-CoV, the increased transmissibility of SARS-CoV-2 is responsible for the increased morbidity and mortality worldwide compared to other beta-coronaviruses. This increased transmissibility stems from SARS-CoV-2 replication in upper respiratory epithelial cells and subsequent nasal and pharyngeal shedding, features not exhibited by SARS-CoV and MERS-CoV. SARS-CoV-2 viral load peaks at TAS-103 about 3-5 days after infection, whereas loads of SARS-CoV and MERS-CoV are maximal after approximately ten days post-symptom onset (8C10). MERS-CoV can also directly infect TAS-103 innate immune cells to augment viral replication, whereas SARS-CoV exhibits abortive infection of these cells. Conclusions regarding potential immune cell infection by SARS-CoV-2 would be premature due to the paucity of current evidence. Further work evaluating SARS-CoV-2 immune cell infection is required to provide a definitive answer. Only two such demonstrations C one in preprint form C exist in current literature, reporting monocyte infection in the alveolar spaces and secondary lymphoid organs (10, 11). ACE2 is unlikely the only receptor mediating SARS-CoV-2 cell entry. A study identified 12 additional receptor types facilitating SARS-CoV-2 Rabbit polyclonal to Bcl6 infection independent of ACE2. Perhaps the expression of such receptors accounts for the broad SARS-CoV-2 tropism and the variable clinical manifestations of COVID-19 (12). For example, Neuropilin-1 binds to the C-end rule (CendR) peptide at the C-terminal end of S1 after proteolytic cleavage of the SARS-CoV-2 S protein. Although the binding affinity between CendR and neuropilin-1 is considerably weaker than RBD-ACE2 interactions, the nasopharynx and upper respiratory tract express neuropilin-1 more abundantly than ACE2 (13). Another receptor, the tyrosine.

Neutrophilia and T-cell lymphopenia manifest as an increased neutrophil to lymphocyte ratio