u/TomasTTEngin

Abstract

Long COVID (LC) - a chronic condition characterized by persistent, debilitating symptoms following SARS-CoV-2 infection - has emerged as a major public health challenge. Although many interrelated mechanisms have been proposed as drivers of LC, the root causes have yet to be identified, posing significant challenges for therapeutic development. While many blood-based studies have been conducted, they have not yielded conclusive mechanistic insights into LC pathogenesis.

Attention has therefore turned toward direct tissue investigation, with the gastrointestinal (GI) tract becoming a major focus due to evidence that virus or viral components can persist at this site for months to years following an episode of COVID-19. Here, we performed a high-dimensional characterization of colorectal tissue and peripheral blood in a highly characterized cohort of 44 people with LC and 13 recovered controls. We profiled SARS-CoV-2 persistence, host immune responses, and tissue inflammation using bulk and single-cell RNA sequencing, nCounter RNA probe hybridization, quantitative PCR, metagenomic next-generation sequencing, plasma proteomics, high-dimensional spectral flow cytometry, in situ-hybridization/immunohistochemistry, and single-cell digital spatial omics.

Our results support a model in which LC is driven by long-term immune dysregulation and perturbations of the regulatory gut immune environment which imply ongoing viral persistence, although direct viral detection was only observed in a subset of participants. Specifically, we identify a tissue-based transcriptional environment in which SARS-CoV-2 activates innate myeloid immune signaling, driving chronic inflammation while simultaneously downregulating pathways responsible for immune-mediated clearance of infected cells, including antigen presentation, phagocytosis, cytotoxic immune cell trafficking, and granzyme production.

Importantly, signatures in peripheral blood are considerably weaker than those observed in tissue. Together, these findings provide a direct biological rationale for therapeutic strategies in LC aimed at enhancing or redirecting cytotoxic immune function to overcome immune dysregulation and clear persistent viral reservoirs.

Abstract

Chronic viral infections are ubiquitous in humans, with individuals carrying multiple viruses that can reactivate during physiological stress, including severe illness1. Notably, SARS-CoV-2 infection has been shown to reactivate chronic viruses such as Epstein–Barr virus and cytomegalovirus, yet the full extent, temporal dynamics and immunological impact of viral reactivation in COVID-19 remain incompletely understood.

Here, leveraging multi-omic longitudinal data from 1,154 hospitalized patients with COVID-19 from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, we reveal significant reactivation of Herpesviridae and Anelloviridae during acute COVID-19, with distinct temporal dynamics for different viruses, and demonstrate that reactivation correlates with disease severity, host immune effects and clinical outcomes.

Although our results do not establish causation between virus reactivation and clinical outcomes, we highlight the prevalence of chronic viral reactivation during acute COVID-19 and long COVID. Our findings challenge the prevailing view that chronic viral reactivation is primarily a consequence of immunosuppression, demonstrating that reactivations occur frequently in immunocompetent individuals during severe illness and in association with increased systemic inflammation. Additionally, we demonstrate persistence of viral reactivation in convalescence, and report an association of Anelloviridae with long COVID. This study provides immune, transcriptomic and metabolomic signatures of viral reactivation that could inform future strategies to prognosticate and treat acute COVID-19 and long COVID.

I came across a buch of studies suggesting sodium butyrate supplementation can help with gut health - if your gut microbiome is screwed up you may lack the bacteria that produce butyrate, which the gut cells need as an input to do their job. It's potentially a gut health vicious circle.

Sodium butyrate is famously hard to supplement because it is absorbed into the blood super fast in the upper digestive tract.

There's only one country, apparently, where sodium butyrate has been taken seriously and they invented a way of encapsulating it so the product can make it to the lower digestive tract. That country is Poland. Apparently over there it's available in every pharmacy, they consider it a basic medicinal staple - like paracetamol or vitamin C or something.

I have bought two types of sodium butyrate, one I am unsure where it came from but it did nothing for me. The other type, the pack was covered in Polish text and it has done things to my digestion that I consider almost like magic.

I have no idea why the rest of the world hasn't caught onto Polish sodium butyrate yet but if you're struggling with fodmaps and your guts and you feel like you've tried everything and nothing has worked yet, I gently suggest researching whether this might be good for you.

(I'm not saying it will cure or help anyone; I do not have any stake in it; I do not recommend any particular brand; and I'm not Polish. I'm just someone who is happy to have found a substance that seems to make a difference and trying to pay it forward.)

The sports i watch, nobody touches the officials, ever.

The checkout situation is 1990-coded, and the whole store is just trapped in time. I bet there's some tinned pineapple at the back of a shelf in there that expired in 2013;

IGAs are usually forced by Metcash to refurb but the owners of this one must have some kompromat on the Metcash bosses because they are not investing a single cent!

Any other IGAs like that?

The problem this would solve is that people are delaying having their first kid for financial reasons.

It is designed not to encourage teen pregnancies or interfere excessively with education. it doesn't kick in *too* early to avoid encouraging people to have kids with their first partner, unwisely.

It would cost a lot but I suspect the multiplier would be strong for wealthy parents and the child welfare upside would be very strong for less wealthy people. I bet the school system would experience fewer problems when kids are raised in less financially strained homes.

If houses have 2 kids in them by age 32 the odds of a third kid presumably rises. Could also add another column and also pay for that third kid I guess!

Age of parent	Baby 1	Baby 2
20	$100	0
21	$200	$0
22	$400	$100
23	$800	$200
24	$1600	$400
25	$3200	$800
26	$6400	$1600
27	$12800	$3200
28	$12800	$6400
29	$12800	$12800
30	$6400	$12800
31	$3200	$6400
32	$1600	$3200
33	$800	$1600
34	$400	$800
35	$200	$400
36	$100	$200
37	0	$100

2021 Melbourne property was an extremely hot market. I lost these two auctions

https://www.realestate.com.au/property/51-heller-st-brunswick-west-vic-3055/ $1.675m for a single story house in west brunswick is crazy.

https://www.realestate.com.au/property/34-ewing-st-brunswick-vic-3056/ 1.63 for this seems less insane but it certainly needed work.

I doubt those have gone up much.

I went on to pay considerably less than those for my house but I did probably overpay and as a result it has not appreciated.

Even though I did overpay, at least I invested less in a market that has cooled considerably!!

We walked past several dogs on this evenings walk with no reaction.

The trick? Sorry to say: 15 years of waiting. Now she is old, completely deaf, partly blind and has spinal issues. She still loves a walk but the desire to fight Every Other Dog? It has finally gone. She is chill. Took me a while to realise because I was still avoiding those dogs . But she doesn't care now.

I have flaired this as a success story because getting this dog successfully to a genuine old age has been a saga. Lot of stress, especially in the early days. I've done 15 years of high alertness daily walks, that's 5000 walks pretty much. My partner has done as many.

Probably at *least* 20,000 roads crossed to avoid other dogs. A couple of bad moments of mismanagement, including vet fees for an off leash miniature poodle (it was fine ), but as the sun goes down I have to say that through perhaps 10,000km of diligently avoiding other dogs I think the dog and I have made it.

In If I Ran the Circus the whale spouts eject water. Which is not what they're for. Whales are mammalian. They inahle and exhale air. Any spray is a mere byproduct.

The misunderstanding is clearer still in If I Had Duck Feet. The whale spout also ejects water - even though the boy wearing it is on land.

I have begun to suspect Seuss's doctorate is not in Marine biology.