4/3/23, SABPA:
'Long-COVID: Clinical manifestations, pathophysiology and therapeutics targets by Avindra Nath M.D.'
“..there was one neurologist I talked to, and after she developed COVID, she was talking to me on the phone and she says that I have to lie down to talk to you I can't even sit up in my bed to talk she would get dizzy every time..”
“..there are other kinds of syndromes that we've known for awhile and they've remained a mystery nobody really understands what's going on with these patients for one is Chronic Fatigue Syndrome, the other is post-Lyme disease, then you have Gulf War Illness..”
‘it's been a real dilemma as to how to really manage these patients and study them so one hope is that as we study Long COVID, all the other illnesses will also benefit from the knowledge gained here..’
“is it possible that there's a persistent viral infection or is it possible that there's immune dysregulation or the two may be interacting with one another, what really is the pathophysiology of Long COVID is the mystery..’
“…what we found was that the biggest pathology really was here in these perivascular region of these blood vessels and we found a lot of fibrinogen over here and this fibrinogen should actually be inside the blood vessel - not outside - and there was leakage of fibrogen suggesting that the there's compromise of the blood-brain barrier and leading to leakage of all these proteins..”
“..what I'm going to show you is that the most of it is likely mediated by antibodies or by macrophages…’
“…you can see there's just excessive amounts of microglia cell activation within the brain so the inflammation really is a key part of what is happening in these individuals…”
“…people have also reported increase in neural filament so it suggests that there's ongoing neural injury taking place and there's protein aggregation taking place in the brains of patients with Long COVID.."
“…if you look at these blood vessels here, you will find that a number of these blood vessels have activated platelets…we found a lot of platelets aggregated around the blood vessels… when we looked at the brain stem, here we found that there were neurons that were atrophic and there’s microglia around them and that suggests that there's neuronophagia taking place…suggests to us that two phenomenon taking place - one was within the blood vessels and the second phenomenon that was taking place was all within the brain stem leading to neuronal damage..”
“..what we think is happening is that most of the pathology occurs at the blood vessel… we think the antibodies attached to the blood vessel, there's rupture of the adhesion molecules - cells and protein then come in, then macrophages that come in and kind of clean up the mess -you get some micro hemorrhages here - the microglial cells then get activated, and then they will attack the neurons and cause neuronal injury..”
“so how do we treat patients..? So we think that a lot of this is immune-mediated…I assured you that there is activation of innate immune responses and hence there are several potential candidates that can be used to dampen the innate immune responses - if there is immune exhaustion in these patients, one can use checkpoint inhibitors – there is a subgroup of patients in which there is there are auto-antibodies that people have reported and so for that subgroup, one can use anti-b cell therapies. And then certainly one can use corticosteroids, but that's not a long-term solution - I will tell you that at least it's an immune phenomenon and you can use it for short periods of time.."
"So, I'd like to conclude by saying that direct invasion of the brain by SARS-CoV-2 is rare and does not explain the neurological complications. Neuroimmune dysfunction is driven by activation of innate immunity immune exhaustion and antibody-mediated phenomenon and clinical trials with immunotherapies could be considered in patients with Long COVID and maybe relevant to other post-infection syndromes."
