The American journal of pathologyOct 20, 2026

Effects of Long-Term Exposure to the COVID-19 Spike Protein in Long COVID and a Mouse Model

Updated Oct 21, 2026

Abstract

The ACE2+ microvasculature density in the CNS increased 19-fold in mice exposed to the SARS-CoV2 spike protein for 1.5 months.

Human fatalities from COVID-19 exhibited an ACE2+ CNS density of 13.2/3.9 compared to 2.1/0.9 in age-matched controls.
Individuals with long COVID showed an ACE2+ microvasculature density of 11.9/3.0 versus 3.5/0.9 in those who recovered from COVID-19.
Viral spike microvasculature density was similar between fatal COVID-19 cases (6.9/2.1) and mice (7.0/4.0), but higher than in people who recovered (0.9/0.3).
Microvasculature collagen 1 deposition was observed in fatal COVID-19 cases, long COVID patients, and in mice exposed to the spike protein for 1.5 months.
SARS-CoV2 spike protein may persist for months to years, contributing to a pro-inflammatory state and fibrosing microangiopathy.

Simplified

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.

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Effects of Long-Term Exposure to the COVID-19 Spike Protein in Long COVID and a Mouse Model

Abstract

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