SARS-CoV-2 Spike Protein and Lung Vascular Cells

“3. Pathology of PAH

PAH [pulmonary arterial hypertension] is a fatal disease without a cure that can affect both males and females of any age, including children. It is a progressive disease, and by the time patients are diagnosed, the thickening of the pulmonary vascular walls has often already occurred. Increased resistance in the pulmonary circulation places strain on the right ventricle, which leads to right heart failure and death. The median overall survival for patients with PAH
is 2.8 years from the time of diagnosis (three-year survival: 48%) without treatment. Even with currently available therapies, the prognosis remains poor, with a three-year survival of PAH patients reported to be only 58–75%...

7. COVID-19 Vaccines and PAH

COVID-19 vaccines currently under consideration, including RNA vaccines (BNT162b2 and mRNA-1273), viral vector-based vaccines (AZD1222 and Ad26.COV2.S), and recombinant protein (NVX-CoV2373), all introduce the SARS-CoV-2 spike protein into the human body. Whether the spike protein elicits cell signaling in host cells and exerts adverse events such as promoting PAH is a question raised in response to the experimental results in cultured cells. RNA and viral vector-based vaccines use human host cells to produce the spike protein; thus, the intracellular spike protein will be produced. The intracellular effects of this foreign molecule on human cells have not been defined …

8. Conclusions

This analysis suggests that the SARS-CoV-2 spike protein and HIV gp120 have the capacity to trigger cell biological events that may lead to the development of pulmonary vascular remodeling and, perhaps, clinically significant PAH, a fatal condition. Given the observations that cells sensitively respond to the spike protein at pM concentrations in cultured cells, it is likely that the SARS-CoV-2 spike protein not only facilitates the viral entry and serves to acquire immunity as an antigen for vaccines but, also, targets host cells and may exert adverse effects (Figure 4). Further experiments should be performed to address the possible effects of the SARS-CoV-2 spike protein on developing PAH. The effects of the SARS-CoV-2 spike protein on the cells of other tissues/organs, such as those of the systemic vasculature, heart, and brain, should also be investigated. Given that this protein will be administered as vaccines to millions and possibly billions of people, it is critical to understand the extracellular and intracellular effects of the SARS-CoV-2 spike protein on human cells that may promote long-term adverse health consequences .”