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.