The biology of coronavirus COVID-19 - including research and treatments

MAIT cell activation and dynamics associated with COVID-19 disease severity

https://immunology.sciencemag.org/content/5/51/eabe1670.full

Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.
 
I'm speaking as a novice here(I mostly do :D ) . But weren't some phase 3-trials in their finishing stages these months and shouldn't results come out for a few of them? Obviously Russia is number one, but are any serious studies underway too?
 
I'm speaking as a novice here(I mostly do :D ) . But weren't some phase 3-trials in their finishing stages these months and shouldn't results come out for a few of them? Obviously Russia is number one, but are any serious studies underway too?

Phase 3 studies of what? Vaccines? Monoclonal antibodies? Antiviral drugs?
 
Neuropathology of patients with COVID-19 in Germany: a post-mortem case series

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30308-2/fulltext

43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes.
In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included.





 


Some interesting speculation there in a very long twitter thread. Some of the things he says I agree with (platelet activation and vasoconstriction in lung microvasculature, leading to a feedback loop), but I think the scenario he described is still incomplete. The activation itself is due to fast build up of immune complexes that is unable to be cleared, leading to the platelet activation in the first place. The fast build up occurs as the pendulum swings from interferon suppression early in the infection to the point which viral load is so high, leading to a rapid increase in immune activity.

The hypothesis about 5-HT build up due to lack of clearance is curious. (if it manages to clear the lung into regular circulation the 5-HT will no longer have much effect)
I suggest this is a local effect, I don't believe there is any evidence of organ failure related to ARDS due to excess platelet derived 5-HT spill over into central circulation.

Farid also believes that longcovid is due to MCAS, but I find this hypothesis unconvincing, due to the lack of overlap of symptoms - (histamine related symptoms for example, and the lack of evidence for a "cytokine storm", even in severe patients)
http://farid.jalali.one/MCAS_COVID.pdf
edit - and this more fleshed out hypothesis that he cites: https://www.sciencedirect.com/science/article/pii/S1201971220307323
 
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The brain stem is one of the systems they felt was wrong in ME. This sounds relevant to us. I had to look up myoclonus but it describes one of my most disabling symptoms.
 
Professor Stephen Holgate is to give Southampton University's Distinguished Lecture on Thursday 15th October from 18.00 to 19.00(BST). The subject is "Understanding and living with COVID-19 -- past, present and future?".

'He said "COVID-19 has caught us all by surprise. From the experience being gained both personally and professionally and in the wider environment, there are important lessons to be learnt - not only about this virus, but about how society ensures we are best prepared to cope now and into the future".'

It seems that the lecture is already oversubscribed but I have registered and am able to email a question to Professor Holgate for the question and answer session. What shall I ask and would it be from me personally or on behalf of the members of Science4ME?
 
What shall I ask and would it be from me personally or on behalf of the members of Science4ME?
It should, I think be from you personally, though you could say you have discussed it with members of S4ME.

How about does he see any parallels with ME/CFS in the symptoms and in the way people with long Covid are being treated by doctors, for example being assumed to have mental health problems such as anxiety.

Or you could say that some doctors who have long Covid are saying on social media that they now have a better understanding of the symptoms of ME and how serious they are, and are sorry they haven't understood their patients with ME previously, and does he have any comment on whether he thinks research on long Covid should also encompass comparisons with ME.
 
It should, I think be from you personally, though you could say you have discussed it with members of S4ME.

Or you could say that some doctors who have long Covid are saying on social media that they now have a better understanding of the symptoms of ME and how serious they are, and are sorry they haven't understood their patients with ME previously, and does he have any comment on whether he thinks research on long Covid should also encompass comparisons with ME.

This sounds good. I may go with that.
 
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