Association of vascular netosis with COVID-19 severity in asymptomatic and symptomatic patients, 2024, Kapoor et al.

[SNT Gatchaman]

Association of vascular netosis with COVID-19 severity in asymptomatic and symptomatic patients
Suman Kapoor; Lucia Mihalovičová; Ekaterina Pisareva; Brice Pastor; Alexia Mirandola; Benoit Roch; Joe Bryant; Anna Philip Princy; Salem Chouaib; Alain Roger Thierry

We examined from a large exploratory study cohort of COVID-19 patients (N = 549) a validated panel of neutrophil extracellular traps (NETs) markers in different categories of disease severity. Neutrophil elastase (NE), myeloperoxidase (MPO), and circulating nuclear DNA (cir-nDNA) levels in plasma were seen to gradually and significantly (p < 0.0001) increase with the disease severity: mild (3.7, 48.9, and 15.8 ng/mL, respectively); moderate (9.8, 77.5, and 27.7 ng/mL, respectively); severe (11.7, 99.5, and 29.0 ng/mL, respectively); and critical (13.1, 110.2, and 46.0 ng/mL, respectively); and are also statistically different with healthy individuals (N = 140; p < 0.0001). All observations made in relation to the Delta variant-infected patients are in line with Omicron-infected patients.

We unexpectedly observed significantly higher levels of NETs in asymptomatic individuals as compared to healthy subjects (p < 0.0001). Moreover, the balance of cir-nDNA and circulating mitochondrial DNA level was affected in COVID-19 infected patients attesting to mitochondrial dysfunction.


Link | PDF (iScience) [Open Access]

 

[SNT Gatchaman]

This was from March. The relevance to Long Covid relates to the findings in asymptomatic patients.

Unexpectedly, the plasma concentrations of the NETs markers in asymptomatic patients were higher than those observed in patients with more severe disease. This observation is most striking for the cir-nDNA marker, which shows values more than twice those of patients with mild condition, and nearly 10 times higher than those of healthy individuals.

the accuracy of our unanticipated observations regarding asymptomatic patients is largely supported by combining NETs proteic markers with cir-nDNA concentration values. This highlights the necessity of combining NETs proteic markers with cir-nDNA in order to obtain a robust interpretation of data. This phenomenon might result from the treatment offered to patients, especially anti-inflammatory and anti-coagulation drugs which are given to those with mild clinical conditions.

An alternative if counterintuitive possibility to consider is that the higher inflammation state of a mild, symptomatic patient may result in greater inhibition of netosis. The slightly but significantly higher degree of netosis, such as observed in asymptomatic cases as compared to healthy individuals, as well as in mild cases (consequently a low grade of inflammation), needs to be confirmed and further investigated.

As a result, the ‘‘asymptomatic’’ clinical condition of those patients could be questioned. This might have medical consequences, given the implication that an uncontrolled NETs production in part of these patients remains a distinct possibility, and offers an explanation of long-term post-infection sequelae, or long COVID. An examination of NETs markers in a large cohort of subjects experiencing long-term sequelae, but who were previously considered as asymptomatic individuals at the time of infection, is needed to evaluate this hypothesis.