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COVID, clotting and long-term recovery - some thoughts
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In the early days of the pandemic, clinical focus was (understandably) on acute management and understanding the disease. However, now that we are many months in, increasing focus is on the recovery and long-term health of people who have been infected.
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For obvious reasons, with a new infectious disease it wasn't known at the start whether this was something that was nasty but you "took it on the chin", recovered, and got back to normal life. Plenty of infectious diseases are like that.
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However, there are increasing personal histories indicating this isn't the case for COVID-19. @GuitarMoog has shared his own experiences, as have many others such as @DaniOliver
3/ https://twitter.com/DaniOliver/status/1279155358666305541?s=20
3/ https://twitter.com/DaniOliver/status/1279155358666305541?s=20
COVID-19 is a complex, multi-organ disease. A lot of stuff is going on. A hyperinflammatory cytokine storm is never good news, the virus may lead to cell death of infected cells, and so on. What I want to pick up here is one aspect of the disease - clotting
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At the start of the pandemic, it soon became clear to frontline clinicians that something was happening with blood clotting. Patients on dialysis, or on ECMO (where blood is pumped thru a machine to get oxygen into it) were seeing their blood clog the tubes of the machines.
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In parallel, autopsy studies were showing instances of multiple blood clots in the lungs of severe covid patients.
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The good news is that clinicians are now aware of this issue, so keep an eye on clotting status of patients in hospital, and have various drugs they can use to control that clotting.
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Very recently, a team at Yale has released a study showing sky-high markers of clotting activation in severe COVID. One of the team reviews the study here:
8/ https://twitter.com/GeorgeGoshuamd/status/1278097990465576965?s=20
8/ https://twitter.com/GeorgeGoshuamd/status/1278097990465576965?s=20
Quick detour into biology. Clotting is a normal function, it's how blood vessels repair themselves after injury. If you've ever cut yourself, you know this. Invisible to the eye, it fulfils a similar function for blood vessels inside your body that get damaged.
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This is coordinated by the cells that line your blood vessels, the endothelial cells. If they get damaged, they release factors that trigger a local clotting reaction so as to fill the hole and allow it to be repaired. Once repaired, that clot is degraded.
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The Yale study and others suggests that in especially severe cases, endothelial cells are producing very high amounts of pro-clotting factors.
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Why this happens is not known, although since SARS-CoV-2 can infect endothelial cells, it could be a direct response to them being infected.
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The lungs are full of endothelial cells because they form the fine blood vessel network that takes oxygen from the lungs and into the blood system. Not hard to see how they would get infected.
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So, if viral infection leads (directly or indirectly) to endothelial cells becoming activated and producing lots of pro-clotting factors, what next? An obvious place clots would form would be the lungs.
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If there are lots of small clots in the lungs, you'd see reduced blood oxygen saturation even though the person was still able to mechanically breathe and get air into their lungs.
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That would fit with the "cryptic hypoxia" symptoms, where blood O2 drops despite the lungs appearing to work. The lungs are working in this model - it's just that some bits aren't getting the blood flow to take the oxygen away.
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Going a bit wider, other organs that might get affected by such microclots would include the kidneys, heart, brain.
The kidney is like a "reverse lung" and again has a diffuse network of fine blood vessels, this time to allow waste materials to pass out
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The kidney is like a "reverse lung" and again has a diffuse network of fine blood vessels, this time to allow waste materials to pass out
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Likewise, the brain is heavily dependent on blood vessels to bring food and oxygen, with consequences if any of them become blocked (eg a stroke).
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It's not hard therefore to extrapolate for clotting to be a potentially significant component of various multi-organ features of COVID, alongside the immunopathology.
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Now to recovery. One can imagine several reasons for ongoing symptoms. Tissue damage (eg due to local hypoxia), ongoing localised hypoxia due to continued clotting, etc.
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This raises questions as to whether dysregulation of clotting continues after the initial acute disease phase (and thus causes sporadic symptoms due to new microclots). If there has been significant endothelial damage, it could take a while before it repairs and calms down.
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But the big question is the extent to which the consequences of this clotting (and potentially ongoing clotting issues) should be monitored during recovery.
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Equally, should we be considering active intervention in the recovery phase, above and beyond the control of coagulation that is now done during hospital treatment.
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This may be particularly relevant for people who get a nasty infection, self-treat at home and don't become hospitalised. Their coagulation status won't be monitored or regulated.
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