Effects of Different Types of Recombinant SARS-CoV-2 Spike Protein on Circulating Monocytes’ Structure

Abstract

This study investigated the biological effects on circulating monocytes after challenge with SARS-CoV-2 recombinant spike protein. Whole blood collected from seven ostensibly healthy healthcare workers was incubated for 15 min with 2 and 20 ng/mL final concentration of recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Samples were analyzed with Sysmex XN and DI-60 analyzers. Cellular complexity (i.e., the presence of granules, vacuoles and other cytoplasmic inclusions) increased in all samples challenged with the recombinant spike protein of the Ancestral, Alpha, and Delta variants, but not in those containing Omicron. The cellular content of nucleic acids was constantly decreased in most samples, achieving statistical significance in those containing 20 ng/mL of Alpha and Delta recombinant spike proteins. The heterogeneity of monocyte volumes significantly increased in all samples, achieving statistical significance in those containing 20 ng/mL of recombinant spike protein of the Ancestral, Alpha and Delta variants. The monocyte morphological abnormalities after spike protein challenge included dysmorphia, granulation, intense vacuolization, platelet phagocytosis, development of aberrant nuclei, and cytoplasmic extrusions. The SARS-CoV-2 spike protein triggers important monocyte morphological abnormalities, more evident in cells challenged with recombinant spike protein of the more clinically severe Alpha and Delta variants.

Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination

“…Immunological system: SARS-CoV-2 spike protein also exerts damaging effects on the immune system, particularly in monocytes, which are part of the innate immune system and are a type of white blood cell that helps destroy infected cells and regulate cellular homeostasis [31]. Recombinant spike protein induces significant monocyte structural abnormalities, including cytoplasmic intrusions, aberrant nuclei, dysmorphia, granulation, vacuolization, and platelet phagocytosis [32]. The deleterious effects were more severe with Alpha and Delta variant SARS-CoV-2 recombinant spike proteins compared to Omicron, indicating a correlation with clinical disease severity [32].…”

“…Recombinant spike protein induces significant monocyte structural abnormalities, including cytoplasmic intrusions, aberrant nuclei, dysmorphia, granulation, vacuolization, and platelet phagocytosis [32]. The deleterious effects were more severe with Alpha and Delta variant SARS-CoV-2 recombinant spike proteins compared to Omicron, indicating a correlation with clinical disease severity [32]. Moreover, spike protein may cause cytokine release syndrome, a hyper-inflammatory response, by activating human monocytes to produce cytokines [33].…”