{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:33:22Z","timestamp":1788968002331,"version":"build-2803163510"},"reference-count":147,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["075-15-2025-013"],"award-info":[{"award-number":["075-15-2025-013"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"award":["075-15-2025-013"],"award-info":[{"award-number":["075-15-2025-013"]}],"id":[{"id":"https:\/\/ror.org\/05dwvd537","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Almazov National Medical Research Center"},{"id":[{"id":"https:\/\/ror.org\/03qepc107","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Post-COVID-19 syndrome (PCS), also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), represents a heterogeneous set of persistent clinical manifestations developing after acute infection. These conditions are associated with immune dysregulation, autonomic imbalance, impaired thymic function, and possible viral persistence. Objective: This study aims to systematically synthesise current evidence on the immunopathogenesis of PCS and to critically evaluate the application of artificial intelligence (AI) and machine learning (ML) approaches for its prediction and clinical stratification. Methods: A PRISMA 2020\u2013informed systematic review was conducted using PubMed\/MEDLINE, Scopus, Web of Science, elibrary.ru and Embase databases (January 2020\u2013December 2025). Studies addressing immunopathological mechanisms and AI\/ML applications in PCS were selected based on predefined eligibility criteria. Risk of bias in prediction studies was assessed using the PROBAST tool. Due to heterogeneity, a structured qualitative synthesis was performed. Current evidence indicates that PCS may result from sustained systemic inflammation, cytokine dysregulation, autoimmunity, and delayed restoration of T-cell homeostasis, including reduced thymic output of na\u00efve T lymphocytes. Persistent thymic dysfunction may contribute to prolonged immune imbalance, increased susceptibility to secondary infections, and reactivation of latent viruses. AI\/ML approaches\u2014including gradient boosting, ensemble learning, deep neural networks, and natural language processing\u2014have demonstrated promising performance across multimodal datasets. However, significant limitations were identified, including small sample sizes, overfitting, lack of external validation, and heterogeneity in outcome definitions. Conclusions: The integration of immunopathological insights with data-driven modelling highlights the potential of combined approaches for improving PCS risk stratification. However, current AI models remain insufficiently validated for clinical implementation. Future research should prioritise methodological standardisation, external validation, and incorporation of mechanistically informed biomarkers.<\/jats:p>","DOI":"10.3390\/microorganisms14061313","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T01:52:08Z","timestamp":1781229128000},"page":"1313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunological Mechanisms and Machine Learning Applications in Post-COVID-19 Syndrome: A Narrative Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6359-0026","authenticated-orcid":false,"given":"Leonid P.","family":"Churilov","sequence":"first","affiliation":[{"name":"Institute of Medicine, Department of Pathology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-6986","authenticated-orcid":false,"given":"Anna","family":"Starshinova","sequence":"additional","affiliation":[{"name":"Faculty of Mathematics and Computer Science, St. Petersburg State University, 199034 St. Petersburg, Russia"},{"name":"Almazov National Medical Research Centre, 197341 St. Petersburg, Russia"},{"name":"Medical Department, Bashkir State Medical University, 450008 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Kudryavtsev","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 197341 St. Petersburg, Russia"},{"name":"Institution of Experimental Medicine, Department of Immunology, 197376 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-5211","authenticated-orcid":false,"given":"Artem","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 197341 St. Petersburg, Russia"},{"name":"Institution of Experimental Medicine, Department of Immunology, 197376 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olesya","family":"Koroteeva","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 197341 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Kulpina","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Department of Pathology, St. Petersburg State University, 199034 St. Petersburg, Russia"},{"name":"Almazov National Medical Research Centre, 197341 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6973-9901","authenticated-orcid":false,"given":"Varvara A.","family":"Ryabkova","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Department of Pathology, St. Petersburg State University, 199034 St. Petersburg, Russia"},{"name":"Medical Department, I.P. Pavlov 1st Saint Petersburg State Medical University, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adilya","family":"Sabirova","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Department of Pathology, St. Petersburg State University, 199034 St. Petersburg, Russia"},{"name":"Medical Department, Bashkir State Medical University, 450008 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Sobolevskaia","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Department of Pathology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2723-4590","authenticated-orcid":false,"given":"Tamara","family":"Fedotkina","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1878-4467","authenticated-orcid":false,"given":"Dmitry","family":"Kudlay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"},{"name":"Institute of Immunology FMBA of Russia, 115478 Moscow, Russia"},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1016\/S1473-3099(21)00703-9","article-title":"A clinical case definition of post-COVID-19 condition by a Delphi consensus","volume":"22","author":"Soriano","year":"2022","journal-title":"Lancet Infect. 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