Expression of SARS-CoV-2 host cell entry factors in immune system components of healthy individuals and its relevance for COVID-19 immunopathology

Abstract

Introduction: Intense immunological dysregulation including immune cell lesions have been characteristically observed in severe cases of Coronavirus Disease-2019 (COVID-19), for which molecular mechanisms are least understood. A study of physiological expressions of SARS-CoV-2 host cell entry related factors in immune system components may help explain molecular mechanisms involved in COVID-19 immunopathology. Materials and Methods: Transcriptomic and proteomic expression metadata for SARS-CoV-2 host cell entry receptor ACE2 and entry associated proteases (TMPRSS2, CTSL, and FURIN) were analysed in silico across immune system components including blood lineage cells. Results: ACE2 was not-detected in any of the studied immune cell components, however, varying transcriptomic and proteomic expressions were observed, for TMPRSS2, CTSL, and FURIN. Conclusions: Non-detectable expressions of SARS-CoV-2 host cell entry receptor ACE2 in immune system components or blood lineage cells indicate it doesn't mediate immune cell lesions in COVID-19. Alternative mechanisms need to be explored for COVID-19 immuno-pathogenesis.

Pathogenesis guided therapeutic management of COVID-19: an immunological perspective

“…It is not clear yet whether this phenomenon is virus inducted or an aberrant host cell immune response. Although, T cells display low expression of SARS-CoV-2 entry receptors [3,49], indicating that the virus mediated T cell demise in the infected individuals effectuates through some other mechanism than through viral receptor signalling [49]. Recent evidence for SARS-CoV-2 mediated atrophy and lesion of the human lymphoid tissue like spleen and lymph nodes provides additional support to this argument which also have negligible expression of the viral entry receptors [50].…”

Neuropilins: C-end rule peptides and their association with nociception and COVID-19

“…In the case of SARS-CoV-2, NRP-1 was found to be up-regulated in the epithelia of olfactory and respiratory cells where it heightens SARS-CoV-2 infection [8] . Though NRP-1 is considerably expressed in immune cells, in situ or in vivo attempts will be required to validate whether NRP-1 is implicated in SARS-CoV-2 invasion of immune cells [16] . NRP-1 was also shown to augment EBV uptake through the epithelia of nasopharyngeal cells, while NRP-2 was found to exhibit an opposing outcome in inhibiting EBV infection [31] .…”