SARS-CoV-2 and Long / POST-COVID

The SARS-CoV-2 disease is directly related to the first defense line of our organism, the so-called innate immunity.

The activated innate immune response to inflammation and inflammatory events such as SARS-CoV-2 infection together or alone with a cytokine storm syndrome will lead to an increased risk of a long-term illness called either post COVID syndrome (< 3 months duration) or long-COVID syndrome (> 3 months duration, from cough and shortness of breath to fatigue, headache, palpitations, chest pain, joint pain, physical limitations, depression, and insomnia). In children, this disease is named today the pediatric inflammatory multiorgan syndrome (PIMS).

Numerous studies published over the last months suggest that SARS-CoV-2 infection unleashed a powerful and uncontrolled inflammatory response that most likely adds to the tissue damages already caused by the viral infection toward the COVID-19 underlying pathology.

In a most recent study [1], kynurenine was identified as being able not only to depict the inflammatory situation during the acute phase of the SARSCoV2 disease but furthermore to give prognostic information.

Our clinical study showed evidence that the level of kynurenine may be used to identify an ongoing subclinical inflammatory situation in patients with long COVID syndrome far beyond measurements of CRP or IL-6.

Salion´s saliva test is based on a specific monoclonal antibody against kynurenine and uses a lateral flow assay (LFA) technology. To our knowledge this is a worldwide unique antibody sensitive enough to cover the given blood concentrations. Furthermore, the assay is able to measure saliva as a prerequisite for a truly non-invasive test format.

We investigated in our study one of the inflammatory markers, kynurenine (Kyn), and the use for diagnosis/detection of the Long-COVID syndrome.

The study compromised in total 151 inpatients with a SARS-CoV-2 infection hospitalized between 03/2020 and 09/2021. The group NC (normal controls) included blood bank donors (n=302,144f/158m, mean age 47.1 ± 18.3 years (range 18-75)).

To further groups were generated based on (Group A n=85, 27f/58m, mean age 63.1 ± 18.3 years (range 19-90), acute admission to the hospital) and (Group B; n=66, 22f/44m, mean age 66.6 ± 17.6 years (range 17-90), admitted either for weaning or for rehabilitation period due to Long-COVID symptoms /syndrome). Plasma concentrations of Kyn, C-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured on admission.

In Group B we determined Kyn 6 weeks after the negative PCR-test. In a subset of patients (n=11) concentrations of Kyn and CRP were measured in sera and saliva 2, 3 and 4 months after dismission. We identified 12 patients with POST-COVID symptoms >20 weeks with still significantly elevated Kyn-levels.

Mean values for NC used as reference were 2.79 + 0.61 µM, range 1.2-4.1 µM. On admission, patients showed significantly higher concentrations of Kyn compared to NC (p-values < 0.001). Kyn significantly correlated with IL-6 peak-values (p=0.411; p-values <0.001) and CRP (p=0.488, p-values<0.001). Kyn values in Group B (Long-COVID) showed still significantly higher values (8.77±1.72 µM, range 5.5-16.6 µM), whereas CRP values in Group B were in the normal range.

Conclusion

Serum and saliva Kyn is reflecting the acute and long-term pathophysiology of the SARS-CoV-2 disease concerning the innate immune response and thus may serve as a useful biomarker for diagnosis and monitoring Long/POST -COVID syndrome and its therapy.


References

[1] Michaelis S, Zelzer S, Schnedl WJ, Baranyi A, Meinitzer A, Enko D. Assessment of tryptophan and kynurenine as prognostic markers in patients with SARS-CoV-2. Clin Chim Acta. 2022 Jan 15;525:29-33. doi: 10.1016/j.cca.2021.12.005. Epub 2021 Dec 10. PMID: 34902346; PMCID: PMC8662911.

Mangge H, Herrmann M, Meinitzer A, Pailer S, Curcic P, Sloup Z, Holter M, Prüller F. Increased Kynurenine Indicates a Fatal Course of COVID-19. Antioxidants (Basel). 2021 Dec 7;10(12):1960. doi: 10.3390/antiox10121960. PMID: 34943063; PMCID: PMC8750518.