Chandelier
Senior Member (Voting Rights)
Effects of prolonged SARS-CoV2 spike protein exposure in long COVID and a mouse model of the disease
Abstract
We addressed the question: can the SARS-CoV2 spike protein persist in ACE2+ endothelia in the CNS/other sites and induce a prolonged microvasculature injury syndrome?
People who died from COVID-19, with age-matched controls, and people with long COVID with symptoms persisting from 1-5 years, with controls of people who had recovered from COVID-19, were studied. Also compared were WT mice injected with the spike protein sacrificed at day 5 versus 1.5 months. The ACE2+ microvasculature density in the CNS increased 19-fold in the mice exposed to spike for 1.5 months. Human fatal COVID-19 cases showed an ACE2+ CNS density of 13.2/3.9 versus 2.1/0.9 for the controls.
Long Covid cases showed an ACE2 microvasculature density of 11.9/3.0 versus 3.5/0.9 for the people who recovered from COVID (each p value < 0.001). Viral spike microvasculature density in the CNS was similar in the fatal COVID-19 cases (6.9/2.1) and mice (7.0/4.0) and in the skin of long-COVID cases (6.0/1.9) and less in people who recovered from COVID-19 (0.9/0.3) (each p < 0.001). Microvasculature collagen 1 deposition was only evident in fatal COVID, long COVID, and in the mice exposed to S1 for 1.5 mo.
Thus, SARS-CoV2 spike (S1) protein can persist for months/years with an associated microvasculature pro-inflammatory state and a restrictive fibrosing microangiopathy; and exposure to high dose S1 markedly increases ACE2 endothelial density.
Web | DOI | The American Journal of Pathology | Paywall
Nuovo, Gerard; Laurence, Jeffrey; Tili, Esmerina; Li, Xing; Magro, Cynthia
Abstract
We addressed the question: can the SARS-CoV2 spike protein persist in ACE2+ endothelia in the CNS/other sites and induce a prolonged microvasculature injury syndrome?
People who died from COVID-19, with age-matched controls, and people with long COVID with symptoms persisting from 1-5 years, with controls of people who had recovered from COVID-19, were studied. Also compared were WT mice injected with the spike protein sacrificed at day 5 versus 1.5 months. The ACE2+ microvasculature density in the CNS increased 19-fold in the mice exposed to spike for 1.5 months. Human fatal COVID-19 cases showed an ACE2+ CNS density of 13.2/3.9 versus 2.1/0.9 for the controls.
Long Covid cases showed an ACE2 microvasculature density of 11.9/3.0 versus 3.5/0.9 for the people who recovered from COVID (each p value < 0.001). Viral spike microvasculature density in the CNS was similar in the fatal COVID-19 cases (6.9/2.1) and mice (7.0/4.0) and in the skin of long-COVID cases (6.0/1.9) and less in people who recovered from COVID-19 (0.9/0.3) (each p < 0.001). Microvasculature collagen 1 deposition was only evident in fatal COVID, long COVID, and in the mice exposed to S1 for 1.5 mo.
Thus, SARS-CoV2 spike (S1) protein can persist for months/years with an associated microvasculature pro-inflammatory state and a restrictive fibrosing microangiopathy; and exposure to high dose S1 markedly increases ACE2 endothelial density.
Graphical abstract
Web | DOI | The American Journal of Pathology | Paywall