Characterization Model of the Post COVID-19 Condition Based on Immunological, Biochemical and Cytokine Markers

Background: The persistence or development of new symptoms three months after the initial acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is referred to as post-coronavirus disease (COVID) condition (PCC). The identification of new biomarkers specific for the occurrence of PCC is vital to proceed in the future towards prediction of its evolution. T-cell dysfunction, cytokine imbalance, and coagulation defects have been reported in PCC. While a wide variety of symptoms associated with PCC has been described, diagnostic biomarker panels are in short supply.Methods: We compared a variety of biomarkers in two age and gender-matched parallel groups (PCC individuals versus participants who had recovered within 3 months after an episode of acute COVID-19 in 2020; n=85 each group). Biomarkers were analyzed 12-24 months after the initial COVID-19 diagnosis to determine a biochemical profile, complete blood cell counts, coagulation status, antibody serology, the counts of specialized lymphocyte populations and levels of cytokines in all participants. Findings: In comparison to controls, PCC individuals showed altered levels of 49 out of 167 markers tested including: circulating K+ levels, αGAD antibodies, antithrombin III, IGFBP3 and IL-10 levels. In addition, the counts of specific lymphocyte subsets (i.e., NK cells and CD8+ effector cells) were significantly altered in PCC participants. Interpretation: We describe a panel based on a limited number of biomarkers (αGAD; IL-10 levels; potassium levels and the presence of circulating CD16brightCD56- cells) that discriminates PCC individuals from recovered individuals with > 88% accuracy and < 92% precision. Funding: This study has been funded by Health Institute Carlos III (ISCIII) through the research grants FIS PI22/01070 and by the European Regional Development Fund (EDRF) “A way of making Europe”. J.S and D.L-I were supported by the HERVCOV project, funded by the HORIZONHLTH-2021-DISEASE project (Personalized medicine and infectious disease: understanding the individual host response to virus) of the European Commission under the Horizon Europe Framework Program. G.A.101057302.Declaration of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Ethical Approval: The project was approved by the Clinical Research Ethics Committee of Aragon (Spain) (protocol reference PI21/278). The study was developed in accordance with the Declaration of Helsinki. Since the project involves the collection and processing of personal data (including personal information) the collection, treatment, communication, and transfer of personal data of all participating subjects comply with the provisions of the General Data Protection Regulation (EU) (GDPR 2016/679) and the applicable national legislation, Organic Law 3/2018, of December 5, on the Protection of Personal Data. Samples and data from patients included in this study were provided by the Biobank of the Aragon Health System (National Registry of Biobanks B. B.0000873) (PT20/00112), integrated in the Platform ISCIII Biobanks and Biomodels and they were processed following standard operating procedures with the appropriate approval of the Ethics and Scientific Committees. Informed consent was obtained from all participants. This study has been reported according to Strengthening the Reporting of Observational studies in Epidemiology STROBE guidelines.