14 Comments
founding

Thank you so much for all your work in gathering and explaining this complex information to us. I was hoping you were going to address the risks of long covid for fully vaxxed and boosted folks. In my blue bubble, people are very scared to unmask because they are worried about long covid. Can you give us some context and information about what we know about that risk?

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Thanks for the very interesting newsletters, it's always great to get a summary of the latest research! I have to point out that one part in this is not correct, however- concerning the pregnancy compensation theory.

>This evolution allowed more protection against a virus during pregnancy.

This is not actually correct, and is wrong also in the Guardian article you linked. The idea behind the pregnancy compensation hypothesis is that during pregnancy, immune reactivity is actually 'dialled down'. The theory says that because the mechanisms that recognize self vs non-self tissues might attack the placenta, which is a mix of parent and offspring tissues, immune reactivity must be lowered.

To compensate for this, immune reactivity is higher during non-pregnant periods- which in a world post-birth control is most of the time for most women. This results in a higher incidence of autoimmune disorders specifically for women. You can see this visualized in the article here: https://pubmed.ncbi.nlm.nih.gov/31200807/#&gid=article-figures&pid=figure-1-key-figure-uid-0

I think it's important to point this out, because the way it is implies that women have more robust immune responses while pregnant, including to SARS-CoV-2- but it's actually more likely to be the opposite. For the story on Long Covid, it's the same result (women have more immune reactivity), but a tiny thing that I think is worth correcting.

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Thank you, as always for helping us make informed decisions. To that end, I'm wondering if there are/will be blood tests available for folks who want to check their IgM and IgG3 antibody levels proactively in order to assess their personal long COVID risk and ease their COVID anxiety. We would be happy to pay for these out of pocket for peace of mind -- or at least an increased peace of mind as we navigate this new world in which most people seem to be partying like it's 1999.

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founding

As someone now in my third year of Long COVID, I have greatly appreciated this series (as well as your work throughout the pandemic). Re: today's NL, two thoughts: 1) I'm less of a fan of the January Cell paper. Its main cohort was >70% hospitalized, so the findings may not apply to the majority of people with Long COVID. 2) on the clinics, they are so oversubscribed they barely exist for most of us -- 2 year waiting lists when they have waiting lists. Some also only see people who were hospitalized in their facility. That's changing (thankfully), but the overall capacity is still just a small fraction of what it should be.

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Thank you Katelyn for these interesting posts. I wondered, in the gender discrepancy of long covid in this last post, whether the varying death rates on gender aren't salient as an additional feature. Perhaps men's higher death rate from covid interrelate with incidences of male long covid because women with long covid did not die, but they continue to struggle, and men who were likely to develop long covid, on the margins, died. It's a small thought.

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Thank you for this series! I began experiencing somewhat extreme symptoms after my second Pfizer vaccine. Two ER visits, with followups to neurologist and cardiologist. Nothing. Finally, PCP did an antibody test and said I had long covid and that the antibodies showed I'd probably had it three months prior to my first vaccine. My husband had been very ill with "allergies" during that time, but I'd never experienced symptoms. Anyway, I'm still struggling with this idea and how to address the ongoing fatigue, anhedonia, etc. I thought the antibodies were due to the vaccine, but PCP said they could see the age of the antibodies? Guess I'm just struggling to accept the diagnosis.

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Hi and thanks for your wonderful work. The citation you gave to support the assertion that the risk of Long Covid may be as much as 4X in women compared to men doesn't touch on that subject at all. Can you provide us with the correct citation(s) for that figure?

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I just found the article link:

https://pubs.acs.org/doi/full/10.1021/jacs.2c03925

Amyloidogenesis of SARS-CoV-2 Spike Protein

Sofie Nyström* and Per Hammarström*

May 17, 2022

Abstract:

SARS-CoV-2 infection is associated with a surprising number of morbidities. Uncanny similarities with amyloid-disease associated blood coagulation and fibrinolytic disturbances together with neurologic and cardiac problems led us to investigate the amyloidogenicity of the SARS-CoV-2 spike protein (S-protein). Amyloid fibril assays of peptide library mixtures and theoretical predictions identified seven amyloidogenic sequences within the S-protein. All seven peptides in isolation formed aggregates during incubation at 37 °C. Three 20-amino acid long synthetic spike peptides (sequence 192–211, 601–620, 1166–1185) fulfilled three amyloid fibril criteria: nucleation dependent polymerization kinetics by ThT, Congo red positivity, and ultrastructural fibrillar morphology. Full-length folded S-protein did not form amyloid fibrils, but amyloid-like fibrils with evident branching were formed during 24 h of S-protein coincubation with the protease neutrophil elastase (NE) in vitro. NE efficiently cleaved S-protein, rendering exposure of amyloidogenic segments and accumulation of the amyloidogenic peptide 194–203, part of the most amyloidogenic synthetic spike peptide. NE is overexpressed at inflamed sites of viral infection. Our data propose a molecular mechanism for potential amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated by endoproteolysis. The prospective of S-protein amyloidogenesis in COVID-19 disease associated pathogenesis can be important in understanding the disease and long COVID-19.

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*IF* this holds up then it could elegantly explain the mechanism behind several postulated causes of Long COVID.

https://scienceblog.com/530702/cause-of-covids-mysterious-bloody-symptom-found/

QUOTED SEGMENTS:

Cause Of Covid’s Mysterious Bloody Symptom Found

May 20, 2022 Linköping University

...researchers at Linköping University (LiU), Sweden, have discovered that the body’s immune system can affect the spike protein on the surface of the SARS-CoV-2 virus, leading to the production of ...amyloid. The discovery of a possible connection between harmful amyloid production and symptoms of COVID-19 has been published in the Journal of American Chemical Society…

Using computer simulation, the researchers discovered that the coronavirus’ spike protein contained seven different sequences which potentially could produce amyloid. Three of the seven sequences met the researchers’ criteria for being counted as amyloid-producing sequences when experimentally tested. They produced, among other things, so-called fibrils…

an enzyme from immune system’s white blood cells can cut up coronavirus’ spike protein. When the spike protein is cut up, it produces the exact piece of protein which, according to the researchers’ analysis, is most likely to produce amyloid. This enzyme is released in large quantities from one type of white blood cells, neutrophils, which are released early on during infections such as COVID-19. When the researchers mixed pure spike protein with this enzyme, called neutrophil elastase, unusual fibrils were produced...

Per Hammarström, professor at the Department of Physics, Chemistry and Biology (IFM) at Linköping University…

Sofie Nyström, who is an associate professor at IFM and the other author on the study.

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In addition to getting vaccinated, boosted, and having the stamina to continue reducing risk with things like masking and ventilation - I am hopeful that antivirals like Paxlovid will also help reduce long Covid incidence.

Paxlovid is currently indicated for high risk individuals to reduce hospitalizations and death. But since it reduces viral loads by 10 FOLD, it can be intuited that taking Paxlovid will reduce long Covid rates. Further surveillance and study is needed to confirm this of course, but it seems logical to me... and a reason to extend treatment to low and medium risk individuals as soon as supplies/ethics allow.

I toiled for a few day on a (paywalled) letter about this specifically, reply to this comment if anyone wants a free version :)

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I would appreciate your (paywalled) letter. I am very interested in the possibilities for ME/ CFS patients at-risk for Long Covid due inability to tolerate current vaccines.

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Ok… Hmmm. I guess sign up for the newsletter and I’ll comp you! You can unsubscribe after that of course

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Good summary. Again. Thank you. I'm digesting what you've summarized and looking at the references.

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founding

Another great article.

In the reading the section “Presence of EBF and autoantibodies

A few questions came to mind

The study indicated that EBV and autoantibodies was higher in long COVID patients (my summary is shortened from the actual statement), the key question is when did the levels increases. Information we don’t have. The second paragraph indicates this information was collected. IF so, what fraction of folks that had high levels of this at the start of the infection did not get long COVID.

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