Since the COVID-19 story broke we have been focusing on the immune system, because after all the immune system will ultimately get rid of the virus. We have made the point that many MS-DMT may not grossly inhibit the cells responsible for the anti-viral response and so MS-DMT may not stop you responding sufficiently to the SARS-CoV-2 virus. More recently we have been suggesting that a central part of the pathology of COVID was due to damage to the vasculature (blood vessels) and clots and that MS and MS-drugs were unlikely to be impacted by this and are unlikely to impact on this. Obviously this is a ongoing story and we have to modify the view as new evidence emerges, at present I do not feel I need to do this yet. Indeed the concept has gained more and more support.
When we first started with our ideas we had knowledge of immunology 101, but was looking to the pathology. So as the neutrophil club was getting their science consortium to get mega bucks in grants, I was asking where are the Neutrophils in the lesions. I had spotted the microthrombi but did not get their significance, because I am not a vascular biologist. It was hard because I was having to use Google translate to try and understand what was going on as most of the articles were written in Chinese and the programme only translated so many characters at a time. I could see blood patches in the lungs but thought theu may be haemorrhage (blood leaking from the vessels rather than blood clots), I got it two days after the first review was revised and submitted and wish I could have updated it. However you have had that information weeks ago.
In this study they looked a severe flu and severe covid and the noticable difference “The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular (inside the cell) virus and disrupted cell membranes”. As we said many weeks ago such damage would liberate clotting factors. There were 9 times more clotting in COVID than in flu and attempts were there to make new blood vessels to get round the problem of clotted vessels
Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D.N Engl J Med. 2020 May 21. doi: 10.1056/NEJMoa2015432.
Background: Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.
Methods: We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression.
Results: In patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth – predominantly through a mechanism of intussusceptive angiogenesis – was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).
Conclusions: In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.).