Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection, Matthews et al, 2024

[John Mac]

n=31

Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection

Abstract
This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months.

LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4+ T cells, PD-1, and TIM-3 expression on CD4+ and CD8+ T cells were observed at 3 and 8 months, but these differences do not persist at 24 months.

Some LC participants had detectable IFN-γ and IFN-β, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC.

No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time.

Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.


https://www.nature.com/articles/s41467-024-47720-8

 

[Hutan]

31 people with Long covid, with these people not necessarily primarily having fatigue - some primarily had breathlessness or chest pain. So, quite a mixed group, and then only 24 people were in the 24 month post-infection followup.

It looks as though LC symptoms were not significantly different between the LC and MC groups at 24 months.

Self-reported health-related quality of life was assessed through the validated EQ-5D-5L index score collected at all timepoints. Participants with LC more often reported problems with mobility, usual activities, and pain/discomfort EQ-5D-5L domains at 4-month visit, but by 24-months no significant differences were observed between the groups (Table 2). Participants with LC had a significantly lower EQ-5D index score 4-months [0.87 (IQR: 0.80, 0.94)] compared to matched controls [0.94 (IQR: 0.92, 1.00); p value: 0.001], however there was no significant difference in median EQ-5D-5L index scores at 24-months by LC status 0.92 (IQR: 0.83, 0.93) and 0.93 (IQR: 0.86, 1.00) for LC and MC, respectively; p value: 0.16 (Fig. 5A–C).

However, on some of the measures, the 'matched controls' got worse, so that may have masked ongoing poor health in the LC group.
By the 24 month mark, 26% of the controls had 'poor health' (up from 16% at 4 months) while 38% of the LC group had 'poor health' (down from 58% at 4 months).

So, it's a bit hard to make much of the findings. It's a frustrating paper. We need information on LC recovery rates, but this paper doesn't help.

 

[rvallee]

Those are actually some marked differences, and it's odd to have matched controls with significant health issues:

The EQ-5D is a very poor instrument for this.

58% of LC participants had an EQ-5D-5L index score below the lower 95% confidence interval of population normative values (“poor health”) at this timepoint versus 16% for matched controls (p = 0.001)

I don't see how this leads to headlines that most problems resolve by 24 months. It seems to have been taken from this:

In summary, our data provides comprehensive evidence that the majority of measures of immunological dysfunction that we and others have previously reported up to 8-months in people with LC have resolved by 2-years in the majority (62%) of people with LC

Which is definitely not the same. And still 38% is quite significant.

For sure this study doesn't really bring any clarity, mostly mud.

 

[Sean]

Long COVID status was assigned if participants reported >1 persistent symptom of dyspnoea, chest pain, or fatigue/malaise at least 90 days after estimated date of initial infection.

Not sure that qualifies as a robust definition of LC.

 

[Yann04]

It is so frustrating to continually see studies like this taken out of context and extrapolated by the media to feed the narrative that Long Covid is begign and short term.