Introduction
The ongoing pandemic of COVID-19 caused by the novel strain of coronavirus, S evere A cute R espiratoryS yndrome Co ronavirus-2 (SARS-CoV-2) has affected millions of lives globally. SARS-CoV-2, an enveloped, positive sense, single stranded RNA virus belongs to genus betacoronavirus of the Coronaviridae family that includes, SARS-CoV-1 and MERS-CoV; the causative agents of respiratory syndrome outbreaks in recent past.1 Receptor recognition by viruses being the foremost step of viral infections is of paramount importance in determining the severity of infections. In the case of SARS-CoV-2, the viral entry to host cells is reported to be primarily mediated by receptor binding domain (RBD) of the viral S (spike) protein to a cell surface receptor ACE2. The recpetor recognition and the ensuing fusion are critical for viral infections that is facilitated by the entry associated protein transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) in concert with FURIN, a host-cell associated protease that mediates the cleavage of the viral spike (S) protein.2,3
Epithelilal cells enriched in ACE2 expression are slectively biased for bearing the viral load and the COVID-19 infections are primarily attracted to lungs via the nasal route, primarily transmitted among people through respiratory droplets and contact routes. The studies indicated organ specific pathogenesis by the SARS-CoV-2 binding-mediated dysregulation of ACE2 (ref). Human ACE2 is an interferon stimulated gene, and thus SARS-CoV-2 may also exploit cell type-specific interferon-driven upregulation of ACE2.4
In severe cases of COVID-19 pathogenesis, a hyperactive innate-immune response characterised by very high level of proinflammation markersknown as ‘cytokine storm’ is observed in lungs as well as other organs. The COVID-19 severity is also characterised by differential response of immune cells; reflected by increased counts of neutrophils and macrophages, however, reduced counts of eosinophil and lymphocytes (specifically of CD4+ and CD8+ T cells).5,6 An increased death of CD4+ and CD8+ T lymphocytes is also a very frequent finding in severe COVID-19.5,7
To delineate, how the immune system components; especially immune related blood-cells, are affected by SARS-CoV-2 infections of an individual, is expected to provide insights on molecular mechanisms involved in immunological dysregulations in COVID-19. Whether the immune system components are potential targets of SARS-CoV-2 or not, would depend on the immune system (cell-types) expression of the receptor ACE2, and the associated cell-entry factors (TMPRSS2 and FURIN). Although, many sporadic reports are available,4,8,9 to our knowledge, this has not been addressed comprehensively, so far. By utilizing the standard databases for transcriptomics (tissue and single cell) and proteomic expressions in human immune-system components; we have performed in silico analysis for evaluating the roles of the expression-levels of host cell-entry factors (ACE2, TMPRSS2, CTSL, and FURIN) for the facilitated entry of SARS-CoV-2 that would lead to immune dysfunctions.