Persistent immune abnormalities discriminate post-COVID syndrome from convalescence, 2024, Sbierski-Kind et al.

Persistent immune abnormalities discriminate post-COVID syndrome from convalescence
Sbierski-Kind, Julia; Schlickeiser, Stephan; Feldmann, Svenja; Ober, Veronica; Grüner, Eva; Pleimelding, Claire; Gilberg, Leonard; Brand, Isabel; Weigl, Nikolas; Ahmed, Mohamed I. M.; Ibarra, Gerardo; Ruzicka, Michael; Benesch, Christopher; Pernpruner, Anna; Valdinoci, Elisabeth; Hoelscher, Michael; Adorjan, Kristina; Stubbe, Hans Christian; Pritsch, Michael; Seybold, Ulrich; Roider, Julia

BACKGROUND
Innate lymphoid cells (ILCs) are key organizers of tissue immune responses and regulate tissue development, repair, and pathology. Persistent clinical sequelae beyond 12 weeks following acute COVID-19 disease, named post-COVID syndrome (PCS), are increasingly recognized in convalescent individuals. ILCs have been associated with the severity of COVID-19 symptoms but their role in the development of PCS remains poorly defined.

METHODS AND RESULTS
Here, we used multiparametric immune phenotyping, finding expanded circulating ILC precursors (ILCPs) and concurrent decreased group 2 innate lymphoid cells (ILC2s) in PCS patients compared to well-matched convalescent control groups at > 3 months after infection or healthy controls. Patients with PCS showed elevated expression of chemokines and cytokines associated with trafficking of immune cells (CCL19/MIP-3b, FLT3-ligand), endothelial inflammation and repair (CXCL1, EGF, RANTES, IL-1RA, PDGF-AA).

CONCLUSIONS
These results define immunological parameters associated with PCS and might help find biomarkers and disease-relevant therapeutic strategies.

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Cohort selection:

n=32 healthy, uninfected controls (HC)
n=32 healthy, previously with SARS-COV-2 infected people without persisting symptoms (CC)
n=27 Long-Covid patients (PC)

I wasn’t able to understand how exactly they ensured the HC group was never infected. It seems they took people from 40 households, of which they new at least one person had been infected and then looked for an uninfected person amongst that household. Seems knowing someone was infected in said household gives a higher chance that a member of the HC group might have been infected as well. These people didn’t show any “seropositive tests for SARS-CoV-2” but they don’t specify which tests were performed. I find that the control cohort part of the study is written far more confusing than it could be.

In any case they tried to select patients and controls well and glancing at Table 1, apart from a focus on people with too short of an illness duration, that seems to be the case. The BMI isn’t too high, the majority of PC patients are female, minimum illness duration is 12 weeks (mean is 4 months), the mean age is 37 years and only few patients were hospitalised (2 patients were hospitalised) and the matching is quite good. There is however one significant difference in the matching with the time that has passed since the acute infection being twice as long in the CC group compared to the PC group.

Most people in the PC cohort have fatigue (93%) and neurological symptoms were also very common. PEM was not assessed, but with a focus on patients that had been ill for a shorter period of time that would in any case probably not be too fruitful. Of course non of that tells us how ill these people were due to PC which is where some focus should be.