Results & Discussion
We have performed in silico analysis of meta-data for
transcriptomic and proteomic expression of SARS-CoV-2 host cell entry
related factors (ACE2, TMPRSS2, CTSL, and FURIN). SARS-CoV-2 host cell
entry receptor ACE2 was not-detected in bulk-transcriptomic and
proteomic expression analysis in any of the studied immune cell
components (bone marrow and lymphoid tissue) (Table 1, Fig. 1). ACE2 was
also not-detected in single cell transcriptomic analysis of blood cell
lineages (Table 2, Fig. 2). ‘Not-detected’ to ‘enriched’ transcriptomic
expression, were observed in bulk (bone marrow and lymphoid tissue) as
well as in single cell analysis (blood cell lineages), and
‘not-detected’ to ‘medium level’ proteomic expression (bone marrow and
lymphoid tissue) expression were observed, for SARS-CoV-2 host cell
entry associated proteases TMPRSS2, CTSL, and FURIN (Table 1-2, Fig.
1-2).
The observations made in this study are important and provide insights
regarding immunopathogenesis in COVID-19. We findings, the
non-detectable level of expressions of viral host cell entry receptor
ACE2, and non-detectable to medium range expression of host cell entry
associated proteases TMPRSS2, CTSL, and FURIN across immune system
components of healthy individuals (Table 1-2, Fig. 1-2) are in line with
recent sporadic studies reporting expression of a single or a set of
these factors across human tissues.4,8,9 The
non-detectable expressions of ACE2 across immune system components
including blood (immune) cells indicate their non-susceptibility for
SARS-CoV-2 infection. However, recent studies have provided indications
of immune cell lesion in COVID-19.12–15Lymphocytopenia in COVID-19 cases is marked by selective killing of T
cells.12 Moreover, SARS-CoV-2 mediated atrophy and
lesion of the human lymphoid tissue— like spleen and lymph nodes—,
also have been observed in a recent study.16 The viral
mediated manipulations of the host immune-cell receptor signaling is
well established fact; however, any such evidence specific to SARS-CoV-2
is currently scarce in literature.17 In absence of
significant cell-surface expression of ACE2 in immune system components,
the alternative mechanisms which are exploited by the COVID-19 virus to
induce immunopathology, need to be ascertained. Therefore, our finding
warrants for a systematic review of existing literature indicated for
the set of plausible mechanisms which may explain immunological
dysregulation in COVID-19 without the involvement of ACE2 signaling. The
available data suggets that either, (i) selective killing of T cells may
be a resultant of high productions of cytokines and pro-inflammatory
markers,15,18 (ii) direct viral protein
toxicity,16 (iii) or presence of an additional
SARS-CoV-2 cell entry receptor which is expressed in immune system
components.19 Recently, a study proposed Neuropilin-1
(NRP1) as an alternative receptor for SARS-CoV-2 cell entry, which has
significant expression in immune cells.19,20 However,
further in situ/in vivo studies will be necessary to prove
that NRP1 can mediate SARS-CoV-2 infection of immune cells.