The microvascular hypothesis underlying neurologic manifestations of long COVID-19 and possible therapeutic strategies, 2021, AbdelMassih

[Andy]

Abstract

With the ongoing distribution of the coronavirus disease (COVID) vaccines, the pandemic of our age is ending, leaving the world to deal with its well-documented aftereffects. Long COVID comprises a variety of symptoms, of which the neurological component prevails. The most permeating theory on the genesis of these symptoms builds upon the development of microvascular dysfunction similar to that seen in numerous vascular diseases such as diabetes. This can occur through the peripheral activation of angiotensin-converting enzyme 2 receptors, or through exacerbations of pro-inflammatory cytokines that can remain in circulation even after the infection diminishes. Several drugs have been identified to act on the neurovascular unit to promote repair, such as gliptins, and others. They also succeeded in improving neurologic outcome in diabetic patients. The repurposing of such drugs for treatment of long COVID-19 can possibly shorten the time to recovery of long COVID-19 syndrome.

Open access, https://journals.lww.com/cardiovasc...cular_hypothesis_underlying_neurologic.1.aspx

 

[TiredSam]

With the ongoing distribution of the coronavirus disease (COVID) vaccines, the pandemic of our age is ending

Really?

 

[Hutan]

Re anosmia (loss of the sense of smell)

Postviral olfactory dysfunction (PVOD) was not only reported in COVID-19, but in other viruses too, such as influenza A, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis, rabies, parainfluenza, adenoviruses, Japanese encephalitis, West Nile, chikungunya, La Crosse, mouse hepatitis, and bunyaviruses [34]. However, Welge-Lüssen et al. [35] reported common cold and influenza to be the most commonly associated with PVOD, with a higher incidence in women and a prevalence ranging from 11% to 40%.

Despite the previous pieces of evidence on the involvement of direct viral invasion in inducing postviral anosmia, microvascular injury of olfactory neurons and bulbs remains the strongest proposed mechanism, as evidenced by MRI brain scans of 13 autopsies, 10 of which showed abnormalities. Specimens studied by Lee et al.showed punctate hyperintensities, interpreted as foci of microvascular injury and fibrinogen leakage. Punctate hypointensities were also detected reflecting microhemorrhages.

More on the microvascular hypothesis:

Furthermore, 19 matched brain samples were also studied in the National Institute of Neurological Disorders and Stroke. In addition to the aforementioned findings, 13 showed perivascular infiltrates, six were found to have acute ischemic hypoxic neurons and five showed activated microglia next to neurons, suggestive of neuronophagia [38].

The microvascular pathogenesis is also emphasized by Aragão et al. [34] who stated that olfactory bulbs showing abnormal enhancement in MRI brain scans of five adult patients are probably the result of micro bleeding.

The long-lasting effects of COVID-19 were proven to be due to vascular abnormalities, namely hypercoagulability and cytokine-mediated injury ending in vascular endothelial damage, microvascular thrombosis, and ischemia, as suggested by Gavriatopoulou et al., Lang et al., Jaunmuktane et al., MacLean et al., and AbdelMassih et al. [5,17,39–41].

I thought this was interesting about a link between nerve damage and 'vein wall signalling' in MS. (I'm not sure what vein wall signalling is actually doing though.)

Interestingly, a microvascular basis was also found in the pathogenesis of MS, as reported by Ge et al. [45]. With the help of 7T ultra-high-field MRI, they were able to delineate a very intimate relation between MS lesions and the anatomical distribution of veins, as the lesions showed a strict perivascular distribution following the form, orientation, and course of vessels.

Moreover, changes in the venous wall signaling as well as an increase in the size of some lesions and decrease in others were detected during follow-up imaging, suggesting a dynamic vascular inflammatory activity [46].

 

[Hutan]

Treatment
They suggest that if something similar to what happens in diabetes in terms of neuropathy/vascular issues is happening, then the drugs developed for helping the problem in diabetes might help.

For example:

Gliptins have been known to be used in the treatment of diabetic patients beside their anti-diabetic effect, they have proven to have anti-inflammatory and vascular relaxation [79], some studies have shown that they might improve neuropathies. ....Interestingly, as gliptins are known to cause little or no hypoglycemic effects, they could also be safely used in non-diabetic patients [81].

I'm getting tired, so will have to stop reading. But I'd be interested to know what any members with diabetes who have been on various drugs think of the possibilities listed in the paper.