[...] T cell activation and exhaustion in plasma are associated with persistent symptoms up to 18 months following [COVID], 2025, Ueland et al

[forestglip]

Markers of T cell activation and exhaustion in plasma are associated with persistent symptoms up to 18 months following mild SARS-CoV-2 infection

Thor Ueland, Rebecca Jane Cox, Annika E. Michelsen, Elisabeth Berg Fjelltveit, Kari Otterdal, Tuva Dahl, Fan Zhou, Rebecca Elyanow, Pål Aukrust, Bjørn Blomberg, Bente E. Halvorsen, Nina Langeland

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Background
Persistent symptoms following SARS-CoV-2 is an increasing problem after COVID-19 disease. The pathogenesis of this persistent post Covid-19 Condition (PCC) is, however, largely unknown. We hypothesized that persistent T cell activation and exhaustion play a role in PCC development.

Methods
We examined plasma levels of soluble (s) CD25, TIM-3 and LAG-3, all markers of T cell activation/exhaustion, by enzyme immunoassays in 170 home-isolated and 53 hospitalized patients for up to 18 months after COVID-19 in relation to persistent symptomatology.

Results
Our major findings were:

(i) Cases with persistent dyspnea and fatigue had markedly higher sCD25 at 6–18 months with a more modest increase in sTIM-3.

(ii) Cases with memory problems at 12–18 months had increased sLAG-3

iii) sCD25 correlated with SARS-CoV-2 antibody titers and microneutralization titers only in cases with PCC while sTIM-3 correlated with these parameters irrespectively of symptoms.

iv) Although hospitalized patients had markedly elevated levels of T cell activation/exhausting markers during follow-up, there was no relation to PCC symptoms.

Conclusion
Our study indicates a role for T cell activation/exhaustion in PCC following home isolated COVID-19 infection, with somewhat different patterns of sCD25, sTIM-3 and sLAG-3, but not in hospitalized COVID-19 patients where disease severity may be more important.

Link | PDF (Front. Immunol.) [Open Access]

 

[Utsikt]

I can’t find an explanation for what they mean by T-cell exhaustion.

Symptoms related to fatigue and cognitive symptoms were recorded by the validated Chalder Fatigue Scale (CFS) (14) which is also validated in the Norwegian general population (15).

The validated Chalder Fatigue Scale (CFS) questions 1, 8, and 11 were used for symptoms of fatigue, impaired concentration, and memory problems using a bimodal score. The prevalence of fatigue, impaired concentration, and memory problems was derived from the corresponding bimodal score of the CFS item 1, 8, and 11, respectively. The severity of dyspnea was also recorded as a bimodal score.

Bimodal means that answering «less/no more than usual» equals 0, and «more/much more than usual» equals 1. You are supposed to compare with the last time you felt good.

I can’t find a direct comparison in the norm data, but a prevalence of fatigue of 31 % at 18 months is way higher than the average for «total fatigue» (both physical and mental) at <14 % for all age groups (fig. 2). It’s also way higher than when compared to the norm for sick people at ~20 % (table IV).

 

[Hutan]

Norwegian study

All home isolated patients had mild disease, and none were hospitalized at any time-point during follow-up.

Thus, of the original study population, we included 170 home-isolated participants who all were sampled at 2, 6 and 12 months and 147 had an additional sample at 18-month follow-up. This study population of home-isolated participants and 53 hospitalized patients with available blood samples is described in Table 1.

All home-isolated and hospitalized patients with available serum samples were included, regardless of if they had PCC.

It doesn't look as though there was undue selection of the home-isolated (acute mild) patients for persistent symptoms in this prospective study. Around 50% of the home-isolated patients were men.

 

[Hutan]

FIGURE 1
T cell activation markers in home-isolated COVID-19 cases during long-term follow-up in relation to persisting symptoms. (A) prevalence of symptoms at 6, 12 and 18 (x-axis) months after infection. Numbers at the top re ect the percentage of patients with symptoms at each time-point. Tukey plots showing plasma levels of (B) soluble (s)CD25 (C) T-cell immunoglobulin and mucin domain 3 (sTIM-3) and (D) Lymphocyte-activationgene 3 (sLAG-3) in relation to symptoms at 6, 12 and 18 months after infection. *p<0.05, **p<0.01 vs. no symptoms. Data were analyzed by multivariate GLM adjusted for age, sex and comorbidities.

Sadly, it's not looking like there is much of an effect there. Just possibly, there is an initial elevation of CD25 in a small proportion of people reporting fatigue, but it is gone by 18 months. Perhaps fatigue is just too common a symptom.

 

[Hutan]

Figure 2, where people with more than one persistent symptom are separated out, is a bit more interesting. This is still just of home-isolated participants. but, there's still only a small number of people with elevated levels.