@PacificNic

I started to post about this on Friday, but decided against it as I don't know what it actually shows in the end. Here's the notes I took at the time:

- Same group that showed "Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection" previously.

https://www.nature.com/articles/s41590-021-01113-x

- Naive B and T cells show improvement between 8 and 24 months.

- Interestingly, AJ Leonardi said previously that age 50 would be an inflection point in immune response, as above that people would not make more naive T cells and the exhaustion would be permanent.

The average age of participants in this study is 50.

- While some things improved between 8 and 24 months(higher levels of PD-1 and TIM-3), some did not.

"A 2.8-fold higher frequency of spike-specific CD8+ T cells were found in LC at 3-months (p = 0.031) that increased at 8-months (5.6-fold; p = 0.007) and was maintained at 24-months (2.7-fold; p = 0.004)"

"Similarly, nucleocapsid-specific CD8+ T cell responses were elevated in LC at 3- (4.2-fold, p = 0.029), 8- (5.1-fold, p = 0.029), and 24- months (1.7-fold, p = 0.034)"

(not a complete list)

- Insanely small sample size for something affecting millions. n=31 with long COVID. 7 of those "lost" before 2 years, so n=24 at the end.

- Only used 3 symptoms to qualify as having long COVID. Fatigue, dyspnea, or chest pain.

- Self reported health scores are subjective, and overall better, but maybe not significantly. For example:

6 of the long COVID cohort reported mobility problems at 8 months, and 5 still did at 24 months.

19 reported anxiety/depression at 8 months and 17 still did at 24. months.

The only things that went down significantly were "usual activities" and "poor health status" both of which could be easily due to adapting to circumstances over 2 years.

Interestingly, part of the reason there was no difference seen in "pain/discomfort" was due mostly to the control group increasing from 23% to 50%, while the long COVID group dropped from 55% to 46%. This is not an indication that the long COVID group "got better" so much as it is that the control group got worse.

- Some blood work did appear to improve by 24 months.

- Importantly, one measure, Pentraxins (PTX3 and CRP) improved and are said to be related to endothelial damage, indicating some improvement in that category.

- They acknowledge small sample size and unusually narrow long COVID definition in their limitations.

- How much is really applicable to other "types" of long COVID?

- Overall, shows some improvement in some people, but given the narrow definition of long COVID and small sample size, this study is getting too much press for what it shows. The real news worthy story would be if they showed ZERO improvement, not if they showed some improvement over two full years.