Why are MS treatments having limited influence on #MSCOVID19


Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study.Goshua G, Pine AB, Meizlish ML et al. :ancet Haematology

What has this got to do with MS and MS-drugs….very little. I think and this is one of the reasons why MS drugs are not influencing COVID-19 in a negative way.

It says that a problem for COVID-19 is that there is damage to the blood vessels and this results in blood clots as a central problem in COVID-19. The clot blocks the vessels making it hard to breathe, but they are also causing all sorts of organ failure. If you have been reading our reviews, we brought this concept to you about two months ago.

This is thought to be in part due to the damage to the vessels facilitating the release something called von Willebrand factor (VWF), which is a pro-blood clotting factor. In more severe COVID-19 you can see it is much higher in the blood (see below) in people in red (intensive care unit = ICU). However you can see it also occurs in people that are not in intensive care….that’s because it probably central to a real problem with the SARS-CoV-2 virus

We had got this in our first paper just but it it is in the latest paper on COVID-19.

David Baker, Charles Roberts, Gareth Pryce, et al. COVID-19 vaccine-readiness for ocrelizumab and other anti-CD20-depleting therapies in multiple sclerosis and other autoimmune diseases. Authorea. June 23, 2020.
DOI: 10.22541/au.159292858.82650822

We have been given assistance to drawn a figure so figure 1 got a make over

Thanks to Alison Schroeer for this

Please note I said limited influence, I won’t say no influence.

However, this is an opinion, there are other views that don’t even consider co-aggulation as a problem

Vallamkondu J, John A, Wani WY, et al. SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets [published online ahead of print, 2020 Jun 27]. Biochim Biophys Acta Mol Basis Dis. 2020;165889. doi:10.1016/j.bbadis.2020.165889. Epithelial cells are tbe lung lining cells, endothelial cells are those lining the blood vessels.

Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study.Goshua G, Pine AB, Meizlish ML et al. :ancet Haematology. Lancet Haematol DOI:https://doi.org/10.1016/S2352-3026(20)30216-7

Summary Background An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19- associated coagulopathy (clotting) , characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell (Blood vessel cell) injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.

Methods In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital. Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range. We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anti-coagulants, and fibrinolytic enzymes. We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable. We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality. Kaplan–Meier analysis was used to further explore the association between biochemical markers and survival.

Findings 68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014). VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients. We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients. In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan–Meier analysis (hazard ratio 5·9, 95% CI 1·9–18·4; p=0·0087).

Interpretation Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.

We have been saying this for weeks. It is in their in our review

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  • Just to situate my reply I have quoted what is probably the most basic component of this topic:
    “In normal conditions, virus-infected cells are destroyed by NK cells of the innate immunity and CD8 positive cytolytic T cells of the adaptive immunity, using perforin-mediated granulysin secretion. This leads to apoptosis of antigen-presenting cells and relevant cytotoxic T cells to avoid unnecessary activation after the antigenic activity is over. However, if a defect occurs in lymphocyte cytolytic activity, whether due to genetic problems or acquired conditions, this may lead to the inability of NK and cytolytic CD8 T cells to lyse infected and activated antigen-presenting cells, resulting in prolonged and exaggerated interactions between innate and adaptive immune cells. In this case, many pro-inflammatory cytokines, including TNF, interferon-γ, IL-1, IL-6, IL-18, and IL-33, are secreted in an unrestrained way causing a cytokine storm.”

    — My feeling on the clotting issue is that “acquired conditions” plays the biggest part with intubation leading the list. For example, if IL-6 is instead tended towards its myokine function by allowing some conscious stress a.k.a cortisol or effort, natural circulation would benefit. Also among “acquired conditions” is the inflammation associated with obesity. This is potentially mediated by the cytokine IL6, and already plays a role in causing poor lung function. Not a good candidate for intubation. Like so many problems, this is probably a level of care issue.

    • Please provide the reference you are quoting from.
      You are citing from immunology 101 because it starts in normal conditions…therefore you are presuming knowledge and where is the evidence that NK cells are involved in COVID19? I am sure there are but SARS was noted for their paucity

      As for “acquired conditons” plays the biggest part in intubation…what does this mean, age? Co-morbiditities? I am sure co-morbititities are very important…look at divergent twins.
      Now to the last bit and killing of APC. The spleens are apparently decimated and it is the lymphocytes that get it.

      IL-6 causing poor lung function, we know that anti-IL-6 can improve some function based on case reports. These issues are not kutally exclsuive however to ignore the coaggulation to think it is all immune is the immunologists view of the world

      I will also point out that the anti-IL-6 receptor in ventilated COVID has just failed

  • One thing that its really strange to me, is why some covid-19 patients develops lymphopenia?

    If your adaptive immune arm is trying to get rid of the virus it would make sense to increase it

    Or it may be some from of regulatory homeostatic apoptosis ?


    Nice post

  • Sorry if this is a dim question (I’m just a pwMS I’m allowed to be dim) but are people in ICU put on heparin? Lying down for ages…. or doesn’t this make any difference?
    What about people on existing anti coagulants ie warfarin, rivaroxaban etc would they help?
    Lay answer please 😉 thanks 🙂

    • Not Dim at all, I was asking this question last week at a covid meeting. Are people put on heparin I would say yes but this is not a simple solution White et al. Heparin resistance in COVID-19 patients in the intensive care unit.J Thromb Thrombolysis. 2020 May 22 : 1–5. doi: 10.1007/s11239-020-02145-0 but is is case of too late again?

  • Am I interpreting the first diagram as indicating most of the damage to blood vessels/risk of clotting is mediated by inflammation. Would immunosuppression be beneficial (provided it doesn’t allow the virus to reign free)?

    • That is one view but the inflammation is due to macrophages and neutrophils and our immunosuppressives are targetting T and B cells…this may be part of reason why steroids work

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