{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T11:03:23Z","timestamp":1781348603062,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council of Republic of China","doi-asserted-by":"publisher","award":["NSTC 113-2313-B-002-032"],"award-info":[{"award-number":["NSTC 113-2313-B-002-032"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Long COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, has emerged as a significant public health challenge with wide-ranging clinical and socioeconomic implications. Developing an effective risk assessment strategy is essential for the early identification and management of individuals susceptible to prolonged symptoms. This study uses a quantitative approach to characterize the dose\u2013response relationships between spike protein concentrations and effects, including Long COVID symptom numbers and the release of proinflammatory mediators. A mathematical model is also developed to describe the time-dependent change in spike protein concentrations post diagnosis in twelve Long COVID patients with a cluster analysis. Based on the spike protein concentration\u2013Long COVID symptom numbers relationship, we estimated a maximum symptom number (~20) that can be used to reflect a persistent predictor. We found that among the crucial biomarkers associated with Long COVID proinflammatory mediator, CXCL8 has the lowest 50% effective dose (0.01 \u03bcg mL\u22121), followed by IL-6 (0.39), IL-1\u03b2 (0.46), and TNF-\u03b1 (0.56). This work provides a comprehensive risk assessment strategy with dose\u2013response tools and mathematical modeling developed to estimate potential spike protein concentration. Our study suggests persistent Long COVID guidelines for personalized care strategies and could inform public health policies to support early interventions that reduce long-term disability and healthcare burdens with possible other post-infection syndromes.<\/jats:p>","DOI":"10.3390\/v17091215","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T14:53:01Z","timestamp":1757083981000},"page":"1215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biomarker-Based Risk Assessment Strategy for Long COVID: Leveraging Spike Protein and Proinflammatory Mediators to Inform Broader Postinfection Sequelae"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0304-1628","authenticated-orcid":false,"given":"Ying-Fei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-2753","authenticated-orcid":false,"given":"Min-Pei","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Taiwan Ocean University, Keelung City 20224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3998-0355","authenticated-orcid":false,"given":"Szu-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jun","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Food Safety and Health Risk Assessment, National Yang Ming Chia Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4440-3138","authenticated-orcid":false,"given":"Shu-Han","family":"You","sequence":"additional","affiliation":[{"name":"Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung City 20224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Hsuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Science Education and Application, National Taichung University of Education, Taichung 403514, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5536-857X","authenticated-orcid":false,"given":"Chi-Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5695-8283","authenticated-orcid":false,"given":"Si-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Hsuan","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-An","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Taiwan Ocean University, Keelung City 20224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-7996","authenticated-orcid":false,"given":"Chung-Min","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","unstructured":"CDC (Centers for Disease Control and Prevention) (2025, May 06). Long COVID or Post-COVID Conditions, Available online: https:\/\/www.cdc.gov\/covid\/long-term-effects\/index.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1001\/jama.2020.22717","article-title":"A proposed framework and timeline of the spectrum of disease due to SARS-CoV-2 infection: Illness beyond acute infection and public health implications","volume":"324","author":"Datta","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e001366","DOI":"10.1136\/bmjmed-2025-001366","article-title":"Long COVID as a long-term condition","volume":"4","author":"Sivan","year":"2025","journal-title":"BMJ Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13643-023-02250-0","article-title":"A systematic review and meta-analysis of Long COVID symptoms","volume":"12","author":"Natarajan","year":"2023","journal-title":"Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"DeVoss, R., Carlton, E.J., Jolley, S.E., and Perraillon, M.C. (2025). Healthcare utilization patterns before and after a Long COVID diagnosis: A case-control study. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-21393-4"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hayes, L.D., Ingram, J., and Sculthorpe, N.F. (2021). More than 100 persistent symptoms of SARS-CoV-2 (Long COVID): A scoping review. Front. Med., 8.","DOI":"10.3389\/fmed.2021.750378"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Abbas, U., Ahmed, I., Afshan, S., Jogezai, Z.H., Kumar, P., Ahsan, A., Rehan, F., Hussain, N., Faheem, S., and Baloch, I.A. (2024). Impact of SARS-CoV-2 viral load on restrictive spirometry patterns in mild COVID-19 recovered middle-aged individuals: A six-month prospective study. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09959-w"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1093\/cid\/ciae539","article-title":"Relationship between acute SARS-CoV-2 viral clearance and Long COVID symptoms: A cohort study","volume":"80","author":"Herbert","year":"2025","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41590-021-01113-x","article-title":"Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection","volume":"23","author":"Phetsouphanh","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109518","DOI":"10.1016\/j.celrep.2021.109518","article-title":"Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms","volume":"36","author":"Peluso","year":"2021","journal-title":"Cell Rep."},{"key":"ref_11","first-page":"e64137","article-title":"The Impact of viral load on the severity and outcome among patients with COVID-19: A cross-sectional study","volume":"16","author":"Shire","year":"2024","journal-title":"Cureus"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"da Silva, S.J.R., de Lima, S.C., da Silva, R.C., Kohl, A., and Pena, L. (2022). Viral load in COVID-19 patients: Implications for prognosis and vaccine efficacy in the context of emerging SARS-CoV-2 variants. Front. Med., 8.","DOI":"10.3389\/fmed.2021.836826"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S2213-2600(23)00142-X","article-title":"Association of SARS-CoV-2 infection and persistence with long COVID","volume":"11","author":"Yang","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Patterson, B.K., Guevara-Coto, J., Yogendra, R., Francisco, E.B., Long, E., Pise, A., Mora, J., Rojas, L., Hlaing, A., and Sutter, K. (2022). Persistence of SARS-CoV-2 S1 protein in CD16+ monocytes in post-acute sequelae of COVID-19 (PASC) up to 15 months post-infection. Front. Immunol., 13.","DOI":"10.1101\/2021.06.25.449905"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"eadi9379","DOI":"10.1126\/sciadv.adi9379","article-title":"Spontaneous, persistent, T cell-dependent IFN-\u03b3 release in patients who progress to Long COVID","volume":"10","author":"Krishna","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Menezes, F., Palmeira, J.D.F., Oliveira, J.D.S., Arga\u00f1araz, G.A., Soares, C.R.J., N\u00f3brega, O.T., Ribeiro, B.M., and Arga\u00f1araz, E.R. (2024). Unraveling the SARS-CoV-2 spike protein long-term effect on neuro-PASC. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1481963"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1016\/j.cmi.2024.09.001","article-title":"Measurement of circulating viral antigens post-SARS-CoV-2 infection in a multicohort study","volume":"30","author":"Swank","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gultom, M., Lin, L., Brandt, C.B., Milusev, A., Despont, A., Shaw, J., D\u00f6ring, Y., Luo, Y., and Rieben, R. (Inflammation, 2024). Sustained vascular inflammatory effects of SARS-CoV-2 spike protein on human endothelial cells, Inflammation, online ahead of print.","DOI":"10.21203\/rs.3.rs-5003230\/v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1038\/s41380-022-01831-0","article-title":"SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein","volume":"28","author":"Albornoz","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"eadg7942","DOI":"10.1126\/science.adg7942","article-title":"Persistent complement dysregulation with signs of thromboinflammation in active Long COVID","volume":"383","author":"Hoch","year":"2024","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/GME.0000000000002490","article-title":"Pre-pandemic leukocyte count is associated with severity of post-acute sequelae of SARS-CoV-2 infection among older women in the Women\u2019s Health Initiative","volume":"32","author":"Ng","year":"2025","journal-title":"Menopause"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gir\u00f3n P\u00e9rez, D.A., Fonseca-Ag\u00fcero, A., Toledo-Ibarra, G.A., Gomez-Valdivia, J.J., D\u00edaz-Resendiz, K.J.G., Benitez-Trinidad, A.B., Razura-Carmona, F.F., Navidad-Murrieta, M.S., Covantes-Rosales, C.E., and Giron-P\u00e9rez, M.I. (2022). Post-COVID-19 syndrome in outpatients and its association with viral load. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192215145"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e487","DOI":"10.1093\/cid\/ciac722","article-title":"Persistent circulating severe acute respiratory syndrome Coronavirus 2 Spike is associated with post-acute Coronavirus Disease 2019 sequelae","volume":"76","author":"Swank","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Palestra, F., Poto, R., Ciardi, R., Opromolla, G., Secondo, A., Tedeschi, V., Ferrara, A.L., Di Crescenzo, R.M., Galdiero, M.R., and Cristinziano, L. (2023). SARS-CoV-2 spike protein activates human lung macrophages. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24033036"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/jimmun\/vkaf033","article-title":"The immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years","volume":"214","author":"Yang","year":"2025","journal-title":"J. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.jval.2022.11.011","article-title":"One-year temporal changes in long COVID prevalence and characteristics: A systematic review and meta-analysis","volume":"26","author":"Huang","year":"2023","journal-title":"Value Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25254","DOI":"10.1073\/pnas.2010722117","article-title":"Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation","volume":"117","author":"Cheng","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Patterson, B.K., Francisco, E.B., Yogendra, R., Long, E., Pise, A., Rodrigues, H., Hall, E., Herrera, M., Parikh, P., and Cabrera-Mora, M. (2021). Immune-based prediction of COVID-19 severity and chronicity decoded using machine learning. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.700782"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41593-020-00771-8","article-title":"The S1 protein of SARS-CoV-2 crosses the blood\u2013brain barrier in mice","volume":"24","author":"Rhea","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12933-021-01359-7","article-title":"Persistent clotting protein pathology in Long COVID\/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin","volume":"20","author":"Pretorius","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"Huang","year":"2020","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5500","DOI":"10.1016\/j.cell.2024.07.054","article-title":"Mechanisms of long COVID and the path toward therapeutics","volume":"187","author":"Peluso","year":"2024","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wynberg, E., Han, A.X., van Willigen, H.D.G., Verveen, A., van Pul, L., Maurer, I., van Leeuwen, E.M., van den Aardweg, J.G., de Jong, M.D., and Nieuwkerk, P. (2024). Inflammatory profiles are associated with long COVID up to 6 months after COVID-19 onset: A prospective cohort study of individuals with mild to critical COVID-19. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0304990"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100663","DOI":"10.1016\/j.xcrm.2022.100663","article-title":"The IL-1\u03b2, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19","volume":"3","author":"Willscher","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tilikete, C., Zamali, I., Meddeb, Z., Kharroubi, G., Marzouki, S., Dhaouadi, T., Ben Hmid, A., Samoud, S., Galai, Y., and Charfeddine, S. (2024). Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-10222-5"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/nyas.15132","article-title":"Long COVID and post-acute sequelae of SARS-CoV-2 pathogenesis and treatment: A Keystone Symposia report","volume":"1535","author":"Durstenfeld","year":"2024","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Low, R.N., Low, R.J., and Akrami, A. (2023). A review of cytokine-based pathophysiology of Long COVID symptoms. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1011936"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Robineau, O., H\u00fce, S., Surenaud, M., Lemogne, C., Dorival, C., Wiernik, E., Brami, S., Nicol, J., de Lamballerie, X., and Blanch\u00e9, H. (2025). Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): A cohort study. eBioMedicine, 117.","DOI":"10.1016\/j.ebiom.2025.105792"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Silva, M.J.A., Ribeiro, L.R., Gouveia, M.I.M., Marcelino, B.D.R., Santos, C.S.D., Lima, K.V.B., and Lima, L.N.G.C. (2023). Hyperinflammatory response in COVID-19: A systematic review. Viruses, 15.","DOI":"10.3390\/v15020553"},{"key":"ref_40","first-page":"e57008","article-title":"Impact of the SARS-CoV-2 spike protein on the innate immune system: A review","volume":"16","year":"2024","journal-title":"Cureus"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"109504","DOI":"10.1016\/j.celrep.2021.109504","article-title":"Systemic IL-15, IFN-\u03b3, and IP-10\/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients","volume":"36","author":"Bergamaschi","year":"2021","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11239-020-02224-2","article-title":"COVID-19: The role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness","volume":"51","author":"Du","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105295","DOI":"10.1016\/j.psyneuen.2021.105295","article-title":"Interleukin-6 as potential mediator of long-term neuropsychiatric symptoms of COVID-19","volume":"131","author":"Kappelmann","year":"2021","journal-title":"Psychoneuroendocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Queiroz, M.A.F., Neves, P.F.M.D., Lima, S.S., Lopes, J.D.C., Torres, M.K.D.S., Vallinoto, I.M.V.C., Bichara, C.D.A., Santos, E.F.D., de Brito, M.T.F.M., and da Silva, A.L.S. (2022). Cytokine profiles associated with acute COVID-19 and Long COVID-19 syndrome. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.922422"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41591-020-01202-8","article-title":"Immune determinants of COVID-19 disease presentation and severity","volume":"27","author":"Brodin","year":"2021","journal-title":"Nat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e70029","DOI":"10.1002\/rmv.70029","article-title":"Oral SARS-CoV-2 infection and risk for Long COVID","volume":"35","author":"Schwartz","year":"2025","journal-title":"Rev. Med. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s10020-024-00986-6","article-title":"Chronic inflammation in post-acute sequelae of COVID-19 modulates gut microbiome: A review of literature on COVID-19 sequelae and gut dysbiosis","volume":"31","author":"Iqbal","year":"2025","journal-title":"Mol. Med."},{"key":"ref_48","first-page":"20","article-title":"Low-grade inflammation in long COVID syndrome sustains a persistent platelet activation associated with lung impairment","volume":"10","author":"Brambilla","year":"2025","journal-title":"Basic Transl. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41591-021-01292-y","article-title":"Attributes and predictors of long COVID","volume":"27","author":"Sudre","year":"2021","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e002528","DOI":"10.1136\/bmjresp-2024-002528","article-title":"Risk of long COVID in patients with pre-existing chronic respiratory diseases: A systematic review and meta-analysis","volume":"12","author":"Terry","year":"2025","journal-title":"BMJ Open Respir. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.cell.2022.01.014","article-title":"Multiple early factors anticipate post-acute COVID-19 sequelae","volume":"185","author":"Su","year":"2022","journal-title":"Cell"},{"key":"ref_52","unstructured":"LabCorp (2025, August 15). SARS-CoV-2 Semi-Quantitative IgG Antibody (Spike). Available online: https:\/\/www.labcorp.com\/tests\/164055\/sars-cov-2-semi-quantitative-igg-antibody-spike."},{"key":"ref_53","unstructured":"LMU Munich (2025, August 15). Long COVID: Spike Protein Accumulation Linked to Long-Lasting Brain Effects. Available online: https:\/\/www.lmu.de\/en\/newsroom\/news-overview\/news\/long-covid-spike-protein-accumulation-linked-to-long-lasting-brain-effects.html."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Patrascu, R., and Dumitru, C.S. (2025). Advances in Understanding Inflammation and Tissue Damage: Markers of Persistent Sequelae in COVID-19 Patients. J. Clin. Med., 14.","DOI":"10.3390\/jcm14051475"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tsilingiris, D., Vallianou, N.G., Karampela, I., Christodoulatos, G.S., Papavasileiou, G., Petropoulou, D., Magkos, F., and Dalamaga, M. (2023). Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202305.1487.v1"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Vassiliou, A.G., Vrettou, C.S., Keskinidou, C., Dimopoulou, I., Kotanidou, A., and Orfanos, S.E. (2023). Endotheliopathy in Acute COVID-19 and Long COVID. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098237"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s40246-025-00810-0","article-title":"MicroRNAs in Long COVID: Roles, Diagnostic Biomarker Potential and Detection","volume":"19","author":"Paval","year":"2025","journal-title":"Hum. Genom."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1186\/s12967-024-05560-6","article-title":"Multi-omics landscapes reveal heterogeneity in long COVID patients characterized with enhanced neutrophil activity","volume":"22","author":"Lin","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e188182","DOI":"10.1172\/JCI188182","article-title":"Long COVID is associated with lower percentages of mature, cytotoxic NK cell phenotypes","volume":"135","author":"Tsao","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"eado2106","DOI":"10.1126\/scitranslmed.ado2106","article-title":"Translating Insights into Therapies for Long Covid","volume":"16","author":"Antar","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/infdis\/jiaf030","article-title":"The current and future burden of Long COVID in the United States (US)","volume":"231","author":"Bartsch","year":"2025","journal-title":"J. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"m3026","DOI":"10.1136\/bmj.m3026","article-title":"Management of post-acute COVID-19 in primary care","volume":"370","author":"Greenhalgh","year":"2020","journal-title":"BMJ"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41586-024-08477-8","article-title":"SARS-CoV-2 evolution on a dynamic immune landscape","volume":"639","author":"Raharinirina","year":"2025","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e221809","DOI":"10.1001\/jamahealthforum.2022.1809","article-title":"The costs of Long COVID","volume":"3","author":"Cutler","year":"2022","journal-title":"JAMA Health Forum"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19","volume":"41","author":"Huang","year":"2020","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/9\/1215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:40:20Z","timestamp":1760035220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/9\/1215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":65,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["v17091215"],"URL":"https:\/\/doi.org\/10.3390\/v17091215","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]}}}