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Soluble SARS-CoV-2 Spike glycoprotein: considering some potential pathogenic effects.

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Summary

The soluble S1 subunit of Spike protein (SP) from SARS-CoV-2 may activate NK cells via TLR2/4, contributing to COVID-19 disease and post-vaccination effects. This mechanism explains varied clinical outcomes and adverse events.

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COVID-19PASCSARS-CoV-2 infectionSpike proteininnate responsepost-mRNA vaccine effects

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Area of Science:

  • Immunology
  • Virology
  • Pathology

Background:

  • The soluble S1 subunit of SARS-CoV-2 Spike protein (SP) is implicated in COVID-19 pathogenesis.
  • NK cells play a role in immune responses to viral infections and may be affected by SARS-CoV-2.
  • Post-acute sequelae of COVID-19 (PASC) and post-vaccination side effects present complex clinical challenges.

Purpose of the Study:

  • To explore the hypothesis that soluble SP directly activates human NK cells.
  • To elucidate the pathogenic role of NK cells in COVID-19 and post-vaccination syndromes.
  • To explain the heterogeneity of clinical outcomes in severe COVID-19, PASC, and post-vaccine adverse events.

Main Methods:

  • Review of existing literature on SARS-CoV-2 Spike protein interactions with immune cells.
  • Analysis of proposed mechanisms involving toll-like receptors (TLR) 2 and 4.
  • Discussion of the biological activities of circulating SP and their impact on cellular processes.

Main Results:

  • Soluble SP may directly bind and activate NK cells via TLR2 and TLR4 in vitro.
  • This activation contributes to NK cell dysfunction and a novel pathogenic role in COVID-19 and post-vaccination effects.
  • Soluble SP triggers multiple cellular responses, including decreased interferon, altered autophagy/apoptosis, cytokine release, and endothelial damage.

Conclusions:

  • Circulating SP's diverse biological activities may explain varied clinical manifestations of COVID-19, PASC, and post-vaccine events.
  • Factors like SP levels, age, and antibody response influence pathological activity.
  • Systematic analysis of excessive SP production is needed to identify at-risk individuals and develop safer vaccines.