{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:29:34Z","timestamp":1768908574777,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Research suggests that periodontal disease may exacerbate symptoms of coronavirus disease (COVID-19). The etiology of this condition has been associated with cytokines such as IL-6. The inflammatory response in COVID-19 can be partially attributed to periodontopathic bacteria and their metabolites. Furthermore, the aspiration of periodontal pathogens and the stimulation of ACE2 expression may lead to an increased production of inflammatory cytokines, potentially worsening COVID-19 symptoms in patients with periodontitis. Materials and Methods: A cross-sectional study was conducted involving patients with both periodontal disease and COVID-19, patients with either condition alone, and healthy subjects. All participants underwent RT-PCR testing for SARS-CoV-2, and a self-reported periodontal disease (Self-RPD) questionnaire was administered. Saliva samples were collected to assess IL-6 levels using the ELISA technique. Results: A total of 28 patients were classified as COVID-19\/Self-RPD+, 32 patients had only COVID-19, 25 were Self-RPD+ only, and 17 were healthy controls. The COVID-19\/Self-RPD+ group frequently exhibited symptoms such as fever, body aches, nasal congestion, and olfactory disturbances and showed significantly higher IL-6 levels compared to the other groups. Cough with phlegm was significantly more frequent in the COVID-19-only group. Additionally, IL-6 levels in saliva were elevated in patients with nasal congestion and in those with 11 or more symptoms in the Self-RPD+ group.<\/jats:p>","DOI":"10.3390\/diagnostics15131650","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T05:00:37Z","timestamp":1751259637000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Periodontal Disease Elevates IL-6 Levels During Initial Symptoms of COVID-19"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0712-0334","authenticated-orcid":false,"given":"Ruth","family":"Rodr\u00edguez-Monta\u00f1o","sequence":"first","affiliation":[{"name":"Departamento de Salud-Enfermedad como Proceso Individual y Colectivo, del Centro Universitario de Tlajomulco, de la Universidad de Guadalajara (CUTLAJO-UdeG), Tlajomulco de Zu\u00f1iga 45641, Jalisco, Mexico"},{"name":"Instituto de Investigaci\u00f3n en Odontolog\u00eda, Departamento de Cl\u00ednicas Odontol\u00f3gicas Integrales, Universidad de Guadalajara, Guadalajara 44100, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4243-4224","authenticated-orcid":false,"given":"Tonatiuh Abimael","family":"Baltazar-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico-Degenerativas, Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Hern\u00e1ndez-Mora","sequence":"additional","affiliation":[{"name":"Especialidad de Periodoncia, Departamento de Cl\u00ednicas Odontol\u00f3gicas Integrales, Universidad de Guadalajara, Guadalajara 44100, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-6866","authenticated-orcid":false,"given":"Mario Alberto","family":"Isiordia-Espinoza","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas, Divisi\u00f3n de Ciencias Biom\u00e9dicas, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitl\u00e1n de Morelos 47620, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatima","family":"Del Muro-Casas","sequence":"additional","affiliation":[{"name":"Dental Academic Unit, Research Department, Universidad Aut\u00f3noma de Zacatecas, Ciudad de Zacatecas 98160, Zacatecas, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4457-704X","authenticated-orcid":false,"given":"Rogelio","family":"Gonz\u00e1lez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Research, School of Dentistry, Universidad Ju\u00e1rez del Estado de Durango, Durango 34000, Durango, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9755-4779","authenticated-orcid":false,"given":"Ronell","family":"Bologna-Molina","sequence":"additional","affiliation":[{"name":"Department of Research, School of Dentistry, Universidad Ju\u00e1rez del Estado de Durango, Durango 34000, Durango, Mexico"},{"name":"Molecular Pathology Area, School of Dentistry, Universidad de la Rep\u00fablica, Montevideo 11600, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8397-1720","authenticated-orcid":false,"given":"Sandra","family":"L\u00f3pez-Verd\u00edn","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Odontolog\u00eda, Departamento de Cl\u00ednicas Odontol\u00f3gicas Integrales, Universidad de Guadalajara, Guadalajara 44100, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ijsu.2020.02.034","article-title":"World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)","volume":"76","author":"Sohrabi","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1136\/postgradmedj-2020-138234","article-title":"Origin, Transmission, Diagnosis and Management of Coronavirus Disease 2019 (COVID-19)","volume":"96","author":"Umakanthan","year":"2020","journal-title":"Postgrad. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Banakar, M., Bagheri Lankarani, K., Jafarpour, D., Moayedi, S., Banakar, M.H., and MohammadSadeghi, A. (2020). COVID-19 transmission risk and protective protocols in dentistry: A systematic review. BMC Oral Health, 20.","DOI":"10.1186\/s12903-020-01270-9"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and Grading of Periodontitis: Framework and Proposal of a New Classification and Case Definition","volume":"89","author":"Tonetti","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mootha, A. (2023). Is There a Similarity in Serum Cytokine Profile Between Patients with Periodontitis or 2019-Novel Coronavirus Infection?\u2014A Scoping Review. Biology, 12.","DOI":"10.3390\/biology12040550"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109969","DOI":"10.1016\/j.mehy.2020.109969","article-title":"Is Periodontal Disease a Risk Factor for Severe COVID-19 Illness?","volume":"144","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Brock, M., Bahammam, S., and Sima, C. (2021). The Relationships Among Periodontitis, Pneumonia and COVID-19. Front. Oral Health, 2.","DOI":"10.3389\/froh.2021.801815"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41368-020-0074-x","article-title":"High Expression of ACE2 Receptor of 2019-NCoV on the Epithelial Cells of Oral Mucosa","volume":"12","author":"Xu","year":"2020","journal-title":"Int. J. Oral Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1021\/acschemneuro.0c00122","article-title":"Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms","volume":"11","author":"Baig","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nor Rashid, N., Amrani, L., Alwan, A., Mohamed, Z., Yusof, R., and Rothan, H. (Mol. Biotechnol., 2024). Angiotensin-Converting Enzyme-2 (ACE2) Downregulation During Coronavirus Infection, Mol. Biotechnol., ahead of print.","DOI":"10.1007\/s12033-024-01277-5"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3000605211002695","DOI":"10.1177\/03000605211002695","article-title":"Nexus between COVID-19 and Periodontal Disease","volume":"49","author":"Sukumar","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1080\/1744666X.2021.1919086","article-title":"The Role of IL-6 and IL-6 Blockade in COVID-19","volume":"17","author":"Potere","year":"2021","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/rmv.2141","article-title":"Interleukin-6 in Covid-19: A Systematic Review and Meta-Analysis","volume":"30","author":"Coomes","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1002\/JPER.20-0455","article-title":"Specific Inhibition of IL-6 Receptor Attenuates Inflammatory Bone Loss in Experimental Periodontitis","volume":"92","author":"Taba","year":"2021","journal-title":"J. Periodontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1007\/s11845-023-03325-6","article-title":"The Effect of Non-Surgical Periodontal Therapy on Salivary IL-6 Levels in Patients with Moderate to Severe Generalized Chronic Periodontitis","volume":"192","author":"Khan","year":"2023","journal-title":"Ir. J. Med. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1002\/jssc.202100384","article-title":"Saliva, a body fluid with recognized and potential diagnostic applications","volume":"44","author":"Boroumand","year":"2021","journal-title":"J. Sep. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/s41591-021-01296-8","article-title":"SARS-CoV-2 Infection of the Oral Cavity and Saliva","volume":"27","author":"Huang","year":"2021","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Santos, C.F., Morandini, A.C., Dion\u00edsio, T.J., Faria, F.A., Lima, M.C., Figueiredo, C.M., Colombini-Ishikiriama, B.L., Sipert, C.R., Maciel, R.P., and Akashi, A.P. (2015). Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134601"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Butera, A., Maiorani, C., Morandini, A., Simonini, M., Colnaghi, A., Morittu, S., Barbieri, S., Ricci, M., Guerrisi, G., and Piloni, D. (2021). Assessment of Oral Microbiome Changes in Healthy and COVID-19-Affected Pregnant Women: A Narrative Review. Microorganisms, 9.","DOI":"10.3390\/microorganisms9112385"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"436.e1","DOI":"10.1016\/j.ajog.2023.12.022","article-title":"The association of post-embryo transfer SARS-CoV-2 infection with early pregnancy outcomes in in vitro fertilization: A prospective cohort study","volume":"230","author":"Li","year":"2024","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s10266-023-00811-2","article-title":"Clinical, Immunological, and Microbiological Analysis of the Association Between Periodontitis and COVID-19: A Case-control Study","volume":"112","author":"Bemquerer","year":"2023","journal-title":"Odontology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bachtiar, B.M., Haerani, N., Soeroso, Y., Ismah, N., and Bachtiar, E.W. (2024). The presence of ACE2 and regulatory miRNAs (miR-200c-3p and miR-421-5p) in the saliva of periodontitis patients post-COVID-19 vaccination. Front. Dent. Med., 5.","DOI":"10.3389\/fdmed.2024.1438139"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Moradi Haghgoo, J., Torkzaban, P., Farhadian, M., and Moosavi Sedeh, S.A. (2023). Association between the severity of periodontitis, COVID-19, C-reactive protein and interleukin-6 levels in hospitalized patients: A case-control study. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-03270-x"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1902\/jop.2016.160196","article-title":"Validity of Self-Reported Periodontal Disease: A Systematic Review and Meta-Analysis","volume":"87","author":"Abbood","year":"2016","journal-title":"J. Periodontol."},{"key":"ref_25","unstructured":"Centers for Disease Control and Prevention (2025, May 23). Symptoms of COVID-19, Available online: https:\/\/www.cdc.gov\/covid\/signs-symptoms\/index.html."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/idj.12170","article-title":"Development and Validation of a Self-Reported Periodontal Disease Measure among Jordanians","volume":"65","author":"Khader","year":"2015","journal-title":"Int. Dent. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1002\/lary.29010","article-title":"Optimum Naso-oropharyngeal Swab Procedure for COVID-19: Step-by-Step Preparation and Technical Hints","volume":"130","author":"Coden","year":"2020","journal-title":"Laryngoscope"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1002\/JPER.17-0719","article-title":"Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"Chapple","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Butera, A., Maiorani, C., Natoli, V., Bruni, A., Coscione, C., Magliano, G., Giacobbo, G., Morelli, A., Moressa, S., and Scribante, A. (2020). Bio-Inspired Systems in Nonsurgical Periodontal Therapy to Reduce Contaminated Aerosol during COVID-19: A Comprehensive and Bibliometric Review. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123914"},{"key":"ref_30","first-page":"1","article-title":"Can Improved Periodontal Health Be a Key Factor in Preventing Severe COVID-19 Complications: An Evidence-Based Review","volume":"2","author":"Bhatia","year":"2021","journal-title":"Adv. Dent."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"88","DOI":"10.9734\/jpri\/2020\/v32i3230937","article-title":"Periodontal Disease and COVID 19","volume":"32","author":"Siddharthan","year":"2020","journal-title":"J. Pharm. Res. Int."},{"key":"ref_32","first-page":"2277","article-title":"Covid-19 and Periodontal Disease\u2014An Overview","volume":"9","author":"Pragya","year":"2020","journal-title":"Int. J. Sci. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/cre2.584","article-title":"Does Periodontitis Influence the Risk of COVID-19? A Scoping Review","volume":"8","author":"Ghosh","year":"2022","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"140","DOI":"10.31436\/ijohs.v4i2.219","article-title":"Molecular Docking Study of Hyaluronic Acid Against Interleukin-6 (7DC8 Protein) in COVID-19 Patients With Periodontitis","volume":"4","author":"Ismail","year":"2023","journal-title":"Iium J. Orofac. Health Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/JPER.21-0272","article-title":"A Case-control Study on the Association Between Periodontitis and Coronavirus Disease (COVID-19)","volume":"93","author":"Anand","year":"2021","journal-title":"J. Periodontol."},{"key":"ref_36","unstructured":"Vilela, A.C.S., Costa, C.A., Perazzo, M.F., Leles, C.R., and Costa, N.L. (2023). Severe Generalized Periodontitis as a Risk Factor for Serious Outcomes of COVID-19: A Structural Equation Modelling Approach. Res. Sq."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6721","DOI":"10.1007\/s00784-022-04631-6","article-title":"Association of Periodontal Therapy, with Inflammatory Biomarkers and Complications in COVID-19 Patients: A Case Control Study","volume":"26","author":"Said","year":"2022","journal-title":"Clin. Oral Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.sdentj.2022.07.001","article-title":"Association Between Periodontitis and COVID-19 Severity in a Tertiary Hospital: A Retrospective Cohort Study","volume":"34","author":"Alolayan","year":"2022","journal-title":"Saudi Dent. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1186\/s12967-021-03198-2","article-title":"Periodontal Disease Increases the Host Susceptibility to COVID-19 and Its Severity: A Mendelian Randomization Study","volume":"19","author":"Wang","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1055\/s-0041-1729139","article-title":"Periodontal Diseases and COVID-19: A Scoping Review","volume":"15","author":"Basso","year":"2021","journal-title":"Eur. J. Dent."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13005-021-00267-1","article-title":"COVID-19 and Periodontitis: Reflecting on a Possible Association","volume":"17","author":"Campisi","year":"2021","journal-title":"Head Face Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1177\/00220345221104725","article-title":"Periodontitis and COVID-19: Biological Mechanisms and Meta-Analyses of Epidemiological Evidence","volume":"101","author":"Baima","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1902\/jop.2011.110207","article-title":"Cytokine Profile in the Gingival Crevicular Fluid of Periodontitis Patients With and Without Type 2 Diabetes: A Literature Review","volume":"83","author":"Javed","year":"2012","journal-title":"J. Periodontol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"333","DOI":"10.2478\/sjecr-2019-0015","article-title":"Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth","volume":"21","author":"Taso","year":"2020","journal-title":"Serbian J. Exp. Clin. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"847","DOI":"10.3892\/etm.2013.1222","article-title":"Assessment of IL-6, IL-8 and TNF-\u03b1 Levels in the Gingival Tissue of Patients With Periodontitis","volume":"6","author":"Noh","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hao, C.-P., Cao, N., Zhu, Y., and Wang, W. (2023). The Impact of Smoking on Periodontitis Patients\u2019 GCF\/Serum Cytokine Profile Both Before and After Periodontal Therapy: A Meta-Analysis. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-02768-8"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mancini, L., Americo, L.M., Pizzolante, T., Donati, R., and Marchetti, E. (2022). Impact of COVID-19 on Periodontitis and Peri-Implantitis: A Narrative Review. Front. Oral Health, 3.","DOI":"10.3389\/froh.2022.822824"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Takahashi, Y., Watanabe, N., Kamio, N., Yokoe, S., Suzuki, R., Sato, S., Iinuma, T., and Imai, K. (2021). Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium Nucleatum in Human Respiratory Epithelial Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031352"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jafrin, S., Aziz, A., and Islam, M.S. (2022). Elevated Levels of Pleiotropic Interleukin-6 (IL-6) and Interleukin-10 (IL-10) Are Critically Involved With the Severity and Mortality of COVID-19: An Updated Longitudinal Meta-Analysis and Systematic Review on 147 Studies. Biomark. Insights, 17.","DOI":"10.1177\/11772719221106600"},{"key":"ref_50","first-page":"120","article-title":"Comparison in Levels of Interleukin 6, Ferritine and Neutrophil-Lymphocyte Ratio in COVID-19 Patiens Treated in ICU and Non-Icu","volume":"16","author":"Oktavia","year":"2022","journal-title":"J. Profesi Med. J. Kedokt. Dan. Kesehat."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Larvin, H., Wilmott, S., Wu, J., and Kang, J. (2020). The Impact of Periodontal Disease on Hospital Admission and Mortality During COVID-19 Pandemic. Front. Med., 7.","DOI":"10.3389\/fmed.2020.604980"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1002\/jmv.26149","article-title":"De Higher Levels of IL-6 Early After Tocilizumab Distinguish Survivors From Nonsurvivors in COVID-19 Pneumonia: A Possible Indication for Deeper Targeting of IL-6","volume":"92","author":"Quartuccio","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41577-021-00536-9","article-title":"Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19","volume":"21","author":"Bonaventura","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/S2213-2600(20)30404-5","article-title":"Cytokine Elevation in Severe and Critical COVID-19: A Rapid Systematic Review, Meta-Analysis, and Comparison With Other Inflammatory Syndromes","volume":"8","author":"Leisman","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e091903","DOI":"10.1136\/bmjopen-2024-091903","article-title":"Vitamin D supplementation for managing COVID-19 in patients with vitamin D deficiency: A systematic review and meta-analysis of randomised controlled trials","volume":"15","author":"Zhu","year":"2025","journal-title":"BMJ Open"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.12998\/wjcc.v8.i17.3763","article-title":"Clinical Efficacy of Tocilizumab Treatment in Severe and Critical COVID-19 Patients","volume":"8","author":"Zeng","year":"2020","journal-title":"World J. Clin. 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