Elevated vascular transformation blood biomarkers in Long-COVID indicate angiogenesis as a key pathophysiological mechanism 2022, Patel et al

[Sly Saint]

Abstract
Background

Long-COVID is characterized by prolonged, diffuse symptoms months after acute COVID-19. Accurate diagnosis and targeted therapies for Long-COVID are lacking. We investigated vascular transformation biomarkers in Long-COVID patients.

Methods
A case–control study utilizing Long-COVID patients, one to six months (median 98.5 days) post-infection, with multiplex immunoassay measurement of sixteen blood biomarkers of vascular transformation, including ANG-1, P-SEL, MMP-1, VE-Cad, Syn-1, Endoglin, PECAM-1, VEGF-A, ICAM-1, VLA-4, E-SEL, thrombomodulin, VEGF-R2, VEGF-R3, VCAM-1 and VEGF-D.

Results
Fourteen vasculature transformation blood biomarkers were significantly elevated in Long-COVID outpatients, versus acutely ill COVID-19 inpatients and healthy controls subjects (P < 0.05). A unique two biomarker profile consisting of ANG-1/P-SEL was developed with machine learning, providing a classification accuracy for Long-COVID status of 96%. Individually, ANG-1 and P-SEL had excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, P < 0.0001; validated in a secondary cohort). Specific to Long-COVID, ANG-1 levels were associated with female sex and a lack of disease interventions at follow-up (P < 0.05).

Conclusions
Long-COVID patients suffer prolonged, diffuse symptoms and poorer health. Vascular transformation blood biomarkers were significantly elevated in Long-COVID, with angiogenesis markers (ANG-1/P-SEL) providing classification accuracy of 96%. Vascular transformation blood biomarkers hold potential for diagnostics, and modulators of angiogenesis may have therapeutic efficacy.

https://molmed.biomedcentral.com/articles/10.1186/s10020-022-00548-8

eta:

Long-COVID has been compared to Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is an overwhelming fatigue that is not improved by rest and worsened by any physical or mental exertion. Our data suggests that Long-COVID is biochemically distinct from ME/CFS as all 14 vascular transformation biomarkers increased significantly in plasma from Long-COVID patients when compared to healthy control subjects. In contrast, plasma levels of P-SEL, MMP-1, ICAM-1, VEGF-A and VEGF-D either do not change with ME/CFS or are depressed (VanElzakker et al. 2019; Roerink et al. 2017; Roerink et al. 2018). In addition, plasma ANG-1 is unchanged or depressed in common autoimmune and inflammatory diseases, such as rheumatoid arthritis (Senna et al. 2013) and systemic lupus erythematosus (Kümpers et al. 2009).

 

[dreampop]

This paper is interesting, the findings of increase in ANG-1 and P-SEL are large in the long covid cohort vs others with no overlap. I don't know how meaningful grouping 14 factors together is, but AUC=1 is quite good, no? I don't know how frequently the ANG-1/P-SEL factors are tested for, but it seems like something that should have come up in other studies if it's meaningful.

On the other hand, the long covid cohort is a group of very poorly defined ("diffuse lingering symptoms") sequential referrals. Having had an intervention, which seems to be any treatment at any point along the way, seem to strongly influence ANG-1, so a much tighter study would need to be done to clear that up.

 

[Jaybee00]

“Second, our data show elevated biomarkers in Long-COVID patients at one to six months (median 98.5 days) after acute infection, with clustering at approximately 100 days, but we did not have longitudinal samples from each of these patients to determine individual biomarker resolution.”

They really need to do longitudinal sampling over a much longer time course before they can declare that LC is distinct from MECFS.

 

[Milo]

“Second, our data show elevated biomarkers in Long-COVID patients at one to six months (median 98.5 days) after acute infection, with clustering at approximately 100 days, but we did not have longitudinal samples from each of these patients to determine individual biomarker resolution.”

They really need to do longitudinal sampling over a much longer time course before they can declare that LC is distinct from MECFS.

Exactly. They would have to compare LC patients with ME pts with similar onset date.

 

[Hutan]

Diagnosing long COVID: Canadian researchers discover unique new clue

What they found was that patients with presumed long COVID had proteins in their blood demonstrating rapid changes in their blood vessels in weeks and months after confirmed COVID-19 infections.

These same biomarkers were not present in patients who did not develop long COVID.

Not only can identifying these elevated proteins be used to diagnose patients with this condition, it also points to processes going on in the body that could help in the development of potential treatments, Fraser said.

https://globalnews.ca/news/9194036/long-covid-canada-researchers-diagnosis/

Link to an article about the study

 

[Hutan]

Using all 14 vascular transformation blood biomarkers, a t-SNE plot illustrated that Long-COVID patients were easily separable from acutely ill COVID-19 inpatients and healthy control subjects (Fig. 1A, B; classification accuracy 88%).

This tells us that people who have had Covid-19 one to 6 months ago are different to healthy controls (I think the healthy controls had never had Covid, as the blood was taken from a blood bank) and also are different to people hospitalised with acute Covid-19.

The healthy control subjects were individuals without disease, acute illness, or prescription medications, and that were previously banked in the Translational Research Centre, London, ON (Directed by Dr. D.D. Fraser; https://translationalresearchcentre.com/)

I don't think it tells us that the people with Long Covid are different to people who had Covid and were recovering without any lingering symptoms - that is, with respect to the 16 biomarkers they looked at. Indeed the elevations of the two molecules identified as most diagnostic are recognised as being helpful in healing.

As COVID-19 patients have increased angiogenesis due to the endothelial injury (Ackermann 2020), the significantly elevated ANG-1 observed in our Long-COVID patients may represent a long-term, wound-repairing angiogenesis response.

They also noted that the people with the highest levels of ANG-1 actually were the ones that didn't need interventions at follow-up

Our study has also identified ANG-1 to be significantly elevated in Long-COVID individuals receiving no interventions at follow-up. There were no sex differences for individuals receiving interventions and those without interventions. These latter findings suggest that ANG-1 is critically important for angiogenesis and it is protective at higher levels, perhaps by hastening the healing response.

I find it a bit amazing that the authors don't even mention the absence of post-Covid healthy controls as a problem in this study.

Perhaps these molecules are important, perhaps post-Covid people without Long Covid have even higher levels when they are recovering from an infection. Perhaps the Long Covid levels are consistent with a normal response to recovery from infection. We can't tell from this study.

(I hope I haven't misunderstood something.)

 

[TigerLilea]

Merged thread

Patients and physicians struggling to officially diagnose long COVID may be one step closer to an answer, thanks to new research from a team of Canadian scientists.

The researchers at Lawson Health Research Institute have discovered patients with post-COVID-19 condition, known as long COVID, have unique signs in their blood that show rapid changes in their blood vessels.

https://globalnews.ca/news/9194036/...KZAwyPoFKCK6c1QsiIDhOD4422Z1NYtdmg7Beu3w-XPms

 

[Creekside]

One of these days there will be a study showing some markers that supposedly differentiate people who spend a lot of time complaining about symptoms vs healthy controls.

 

[Sean]

One of these days there will be a study showing some markers that supposedly differentiate people who spend a lot of time complaining about symptoms vs healthy controls.

Yeah, I want to see the brains scans on people who lust for power over other people.