Microvascular Destruction: SARS-CoV-2 Mpro and Spike Protein Create String Vessels

The slow, progressive destruction of the microvasculature can explain the pathogenesis of Long COVID and Spike Protein disease/injury.

A typical example of a lectin stain for capillaries is shown in A. Scale bar represents 100µm. Following bed rest, capillary-to-fiber ratio was not significantly different (B), while patients with ME/CFS had a significantly lower capillary-to-fiber ratio compared to patients with long COVID and healthy controls. Capillary density (C) was significantly increased following bed rest, while both patients with long COVID and patients ME/CFS had significantly lower capillary densities compared to healthy controls (D). The relationship between fiber cross-sectional area (FCSA) and capillary-to-fiber ratio significantly correlated in all conditions (albeit P=0.062 following bed rest). The relationship between FCSA and capillary-to-fiber ratio was not significantly different following bed rest (z=0.495, P=0.621), however compared to healthy controls, both patients with long COVID (z= - 2.176, P=0.030) and patients with ME (z= −2.602, P=0.009) displayed significantly different relationships (G). Capillary density and capillary-to-fiber ratio data were normally distributed following Box-Cox transformation. Paired t-tests were used to assess parametric data from the bed rest cohort. Non-parametric data from the bed rest cohort was assessed using Mann–Whitney U test. ANOVA, with Tukey HSD post-hoc testing or Kruskal–Wallis H test, with pairwise Wilcoxon tests with Benjamini–Hochberg correction post-hoc for patient cohorts. Linear relationships were assessed using Pearson’s correlation on non-transformed data. Solid lines represent significant correlations, dashed lines represent correlations with P<0.10.

A preprint was published last week which, I believe, shines a great light on understanding what Long COVID/Spike Protein disease/injury is and how it progresses. An interesting study was conducted. A group of healthy controls were given strict 60-day bedrest and their skeletal muscle properties were then compared with those who have Long COVID and ME/CFS. A very revealing observation was made. Those who had Long COVID and ME/CFS did not suffer muscle atrophy but had reduced capillaries.

Bed rest caused muscle atrophy, and the reduced oxidative phosphorylation related to reductions in maximal oxygen uptake. Patients with long COVID and ME/CFS did not have muscle atrophy, but had less capillaries and a more glycolytic fibers, none of which were associated with maximal oxygen uptake. While the whole-body aerobic capacity is similar following bed rest compared to patients, the skeletal muscle characteristics differed, suggesting that physical inactivity alone does not explain the lower exercise capacity in long COVID and ME/CFS.

Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest
https://www.medrxiv.org/content/10.1101/2025.05.02.25326885v1.full-text

This brought to mind a paper I had read about the brains of 36 COVID autopsies. ALL of them had string vessels.

All cases had many atrophic or regressed (‘string’) capillaries appearing as tubes with a narrow or collapsed and usually empty lumen. Some similar but lengthy microcirculatory channels may have been pre-capillary arteriolar shunts or postcapillary venules rather than capillaries (Fig. 3E). In most cases ‘ghost’ capillaries with no mural nuclei or luminal contents were identified, and these were occasionally frequent at least focally.

Reactive and acute inflammatory microvasculopathy in 36 COVID-19 autopsy brains
https://europepmc.org/article/ppr/ppr489756

In the context of what I have called SPED (Spike Protein Endothelial Disease), this makes perfect sense. The creation of String Vessels - capillaries that have had their Endothelium destroyed.

What is a String Vessel?

String vessels are thin connective tissue strands, remnants of capillaries, with no endothelial cells; they do not carry blood flow. They occur in numerous species, particularly in the central nervous system, but can occur in any tissue where capillaries have died. String vessels are often associated with pathologies such as Alzheimer’s disease, ischemia, and irradiation, but are also found in normal human brains from preterm babies to the aged.

A Review of String Vessels or Collapsed, Empty Basement Membrane Tubes
https://pmc.ncbi.nlm.nih.gov/articles/PMC3081641/

This knowledge, combined with the understanding that SARS-CoV-2 Mpro and Spike Protein induce String Vessels can explain virtually all of Long COVID – and Spike Protein disease/injury.

Metabolic dysfunction or apoptosis of BMECs may also play a role in BBB disruption during COVID-19. String vessels are collapsed blood vessels no longer capable of blood flow and are associated with vascular dysfunction during neurodegenerative diseases. Analysis of post-mortem COVID-19 brain tissue identified increased string vessel formation and vessel apoptosis [54]. Investigation using an in vitro endothelial cell line and intravenous delivery to mice of an adenoviral vector identified SARS-CoV-2 main protease (Mpro), as a potential inducer of string vessel formation. Mechanistically, the addition of Mpro to endothelial cells degraded the NFkB modulator, Nemo, which induced a receptor-interacting serine/threonine kinase 3 (RIPK3)-dependent apoptotic pathway [54]. The addition of S protein to in vitro endothelial cells did not cause changes in viability, but it did induce morphological alterations toward a contractile state, which is a sign of cell stress, and it inhibited mitochondrial function in a pericyte cell line [55,56].

Neuroinflammation and COVID-19
https://www.sciencedirect.com/science/article/pii/S0959438822001027

This is all related to the Extracellular Matrix – echoing my previous observation that the Spike Protein turns us into a mass of “living cartilage.”

String vessels have been shown to begin as empty BM (Basement Membrane) tubes, after endothelial cell destruction. Several names for these structures appear in the literature, so an attempt at unifying the terminology may be useful. When the capillary first loses its endothelial cells, it becomes an empty BM tube. This clear and descriptive name may be preferable to acellular capillary, because such tubes no longer carry blood. The empty BM tube soon collapses into a string of collagen, leaving a trace of the destroyed capillary. At this stage it could well be described as a collagen strand, but the name string vessel may perhaps be better because it adds the information that this collagen strand is the remnant of a vessel.

A Review of String Vessels or Collapsed, Empty Basement Membrane Tubes https://pmc.ncbi.nlm.nih.gov/articles/PMC3081641/

String Vessels are a hallmark of both AD and PD. Just as I have proposed we view SARS-CoV-2/Spike Protein induced autoimmune disease not as the development of discrete diseases but as the result of Macrophage Activation, we should also view what is happening in the brains (and other organs) of victims differently as well. It is not that the virus and the protein cause AD/PD, for example, but that they destroy the microvasculature.

Background: String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD).

Conclusions: Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region.

String Vessel Formation is Increased in the Brain of Parkinson Disease
https://pubmed.ncbi.nlm.nih.gov/26444086/

It is my hope that this understanding will assist us in finding therapeutics to address these underlying issues that the virus and its proteins cause. I will continue to study and to report my findings. Thank you, as always, for your dialogue, readership and support. You keep me going – and I am forever grateful.