{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:10:15Z","timestamp":1785431415702,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationEU","award":["SFZG-15-2025"],"award-info":[{"award-number":["SFZG-15-2025"]}]},{"award":["SFZG-15-2025"],"award-info":[{"award-number":["SFZG-15-2025"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Cervical necrotizing fasciitis (CNF) is a rare but rapidly progressive deep-neck infection. Reports suggest a rising incidence after the COVID-19 pandemic, but host-response biomarkers remain poorly characterized. We evaluated whether the pandemic\/post-pandemic era was associated with higher CNF frequency and a distinct immunonutritional profile. Methods: Retrospective cohort at a Croatian national tertiary referral center. Adults with CNF were grouped by admission era: pre-pandemic (2010\u20132019; n = 11; 10.00 years) and pandemic\/post-pandemic (January 2021\u2013April 2026; n = 15; 5.29 years). Incidence was compared by Poisson rate ratio (IRR). Admission biomarkers included classical indices (NLR, PLR, LMR, SII, AISI) and albumin-integrated composites (CAR, NAR, NPAR, PNI, CALLY, CAR\/PNI, SIRI\/albumin, AISI\/albumin). Mann\u2013Whitney U and Fisher\u2019s exact tests were used with the Benjamini\u2013Hochberg FDR correction; ROC analysis with bootstrap 95% CIs assessed era discrimination. Results: Incidence rose 2.6-fold (IRR = 2.58; 95% CI 1.18\u20135.61; p = 0.021); sensitivity analysis excluding 2026 was consistent (IRR = 2.36; p = 0.048). All 21 odontogenic cases originated from mandibular culprit teeth. Comorbidities (27% vs. 67%) and complications (27% vs. 53%) were more frequent in the pandemic\/post-pandemic era, while overall mortality was 11.5%. Among the evaluated biomarkers, NPAR (q = 0.030) and CAR\/PNI (q = 0.030) showed the strongest discriminatory performance for era classification (AUC 0.867 and 0.855, respectively) within this exploratory cohort. Streptococci fell from 82% to 33% (p = 0.021); S. pyogenes disappeared, S. anginosus\/constellatus persisted, and atypical organisms (Acinetobacter, Candida, Corynebacterium) emerged exclusively post-pandemic (0% vs. 20%). Conclusions: Pandemic\/post-pandemic CNF was more frequent, more comorbid, and biologically distinct, with a coherent hypoalbuminemic hyperinflammatory profile with diversified microbiology. In this single-center cohort, these associations are exploratory and hypothesis-generating, and the era label denotes a calendar period rather than a confirmed individual SARS-CoV-2 infection. NPAR and CAR\/PNI emerged as the most promising exploratory biomarkers and warrant prospective multicenter validation.<\/jats:p>","DOI":"10.3390\/jcm15145350","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"5350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cervical Necrotizing Fasciitis Across the COVID-19 Pandemic: A Single-Center Exploratory Retrospective Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-1278","authenticated-orcid":false,"given":"Marko","family":"Tarle","sequence":"first","affiliation":[{"name":"Department of Maxillofacial and Oral Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9203-7254","authenticated-orcid":false,"given":"Marina","family":"Ragu\u017e","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-9163","authenticated-orcid":false,"given":"Igor","family":"\u010cvrljevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial and Oral Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7058-4123","authenticated-orcid":false,"given":"Koraljka","family":"Hat","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial and Oral Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-2037","authenticated-orcid":false,"given":"Ivica","family":"Luk\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial and Oral Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1056\/NEJMra1600673","article-title":"Necrotizing Soft-Tissue Infections","volume":"377","author":"Stevens","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1002\/hed.25184","article-title":"Cervical necrotizing fasciitis: Systematic review and analysis of 1235 reported cases from the literature","volume":"40","author":"Gunaratne","year":"2018","journal-title":"Head Neck"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1111\/bjd.15615","article-title":"Henri Mondor Hospital Necrotizing Fasciitis Group. Mortality of necrotizing fasciitis: Relative influence of individual and hospital-level factors, a nationwide multilevel study, France, 2007\u20132012","volume":"177","author":"Audureau","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3390\/surgeries5030042","article-title":"Cervical Necrotizing Fasciitis in Adults: A Life-Threatening Emergency in Oral and Maxillofacial Surgery","volume":"5","year":"2024","journal-title":"Surgeries"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bottger, S., Zechel-Gran, S., Schmermund, D., Streckbein, P., Wilbrand, J.F., Knitschke, M., Pons-Kuhnemann, J., Hain, T., Weigel, M., and Imirzalioglu, C. (2022). Odontogenic Cervicofacial Necrotizing Fasciitis: Microbiological Characterization and Management of Four Clinical Cases. Pathogens, 11.","DOI":"10.3390\/pathogens11010078"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12610-022-00162-y","article-title":"Management of Fournier\u2019s gangrene during the COVID-19 pandemic era: Make a virtue out of necessity","volume":"32","author":"Paladini","year":"2022","journal-title":"Basic Clin. Androl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1089\/sur.2023.233","article-title":"Increase in Streptococcal Necrotizing Fasciitis During and After the Coronavirus Disease 2019 Pandemic","volume":"25","author":"Breidung","year":"2024","journal-title":"Surg. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1177\/00031348221074251","article-title":"The Epidemiology of Necrotizing Fasciitis at a Rural Level 1 Trauma Center During the COVID-19 Pandemic","volume":"89","author":"McGee","year":"2023","journal-title":"Am. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100413","DOI":"10.1016\/j.ijregi.2024.100413","article-title":"Necrotizing fasciitis of the head and neck in era of COVID-19: A single-institution experience","volume":"12","author":"Zadjali","year":"2024","journal-title":"IJID Reg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102145","DOI":"10.1016\/j.jormas.2024.102145","article-title":"Facing a new reality: Significant increase in necrotizing fasciitis in the post-COVID era?","volume":"126","author":"Nadjmi","year":"2025","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1007\/s15010-025-02564-2","article-title":"A rise in severe necrotizing fasciitis- another consequence of the COVID-19 pandemic?","volume":"53","author":"Eijkenboom","year":"2025","journal-title":"Infection"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1007\/s00268-023-07040-2","article-title":"Necrotising Fasciitis During the COVID-19 Pandemic: An Australian Hospital Network Experience","volume":"47","author":"Nguyen","year":"2023","journal-title":"World J. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100488","DOI":"10.1016\/j.ijso.2022.100488","article-title":"Necrotising fasciitis in the COVID-19 era: A consequence of caution\u2014A case series","volume":"43","author":"Feeney","year":"2022","journal-title":"Int. J. Surg. Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s10654-018-0472-y","article-title":"The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: The Rotterdam Study","volume":"34","author":"Fest","year":"2019","journal-title":"Eur. J. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6212","DOI":"10.1158\/1078-0432.CCR-14-0442","article-title":"Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ranzani, O.T., Zampieri, F.G., Forte, D.N., Azevedo, L.C., and Park, M. (2013). C-reactive protein\/albumin ratio predicts 90-day mortality of septic patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059321"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yang, M., Lin, S.Q., Liu, X.Y., Tang, M., Hu, C.L., Wang, Z.W., Zhang, Q., Zhang, X., Song, M.M., and Ruan, G.T. (2023). Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1131496"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tarle, M., Cvrljevic, I., Hat, K., Raguz, M., Salaric, I., and Luksic, I. (2026). C-Reactive Protein-to-Platelet Inflammatory Index (CPII) and Symptom Severity Score for Early Differentiation of Odontogenic Cervicofacial Necrotizing Fasciitis from Odontogenic Abscesses: A Retrospective Cohort Study. Dent. J., 14.","DOI":"10.3390\/dj14030162"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.hpb.2021.06.414","article-title":"Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma","volume":"24","author":"Iida","year":"2022","journal-title":"HPB"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.ctrv.2012.08.003","article-title":"The systemic inflammation-based Glasgow Prognostic Score: A decade of experience in patients with cancer","volume":"39","author":"McMillan","year":"2013","journal-title":"Cancer Treat. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"107233","DOI":"10.1016\/j.intimp.2020.107233","article-title":"Neutrophils and COVID-19: The road so far","volume":"90","author":"Carvalho","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rowlands, M., Segal, F., and Hartl, D. (2021). Myeloid-Derived Suppressor Cells as a Potential Biomarker and Therapeutic Target in COVID-19. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.697405"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.imlet.2020.06.013","article-title":"Lymphopenia during the COVID-19 infection: What it shows and what can be learned","volume":"225","author":"Tavakolpour","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1002\/jmv.26003","article-title":"Hypoalbuminemia predicts the outcome of COVID-19 independent of age and co-morbidity","volume":"92","author":"Huang","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41590-023-01724-6","article-title":"Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2","volume":"25","author":"Yin","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101401","DOI":"10.1016\/j.beha.2022.101401","article-title":"COVID-19 disease and immune dysregulation","volume":"35","author":"Davitt","year":"2022","journal-title":"Best Pr. Res. Clin. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102622","DOI":"10.1016\/j.jiph.2024.102622","article-title":"Invasive group A streptococcal infections as a consequence of coexisting or previous viral infection in the post-COVID-19 pandemic period","volume":"18","author":"Mania","year":"2025","journal-title":"J. Infect. Public Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/j.bjoms.2020.09.014","article-title":"Impacts of lockdown during the SARS-CoV-2 pandemic on patients presenting with cervicofacial infection of odontogenic origin: A comparative study","volume":"59","author":"Dawoud","year":"2021","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijsu.2020.07.002","article-title":"Acute Care Surgery during the COVID-19 pandemic in Spain: Changes in volume, causes and complications. A multicentre retrospective cohort study","volume":"80","author":"Morales","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jpen.1451","article-title":"Hypoalbuminemia: Pathogenesis and Clinical Significance","volume":"43","author":"Soeters","year":"2019","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tran, S., Pullano, K.J., Henry, S., and Ribeiro, M.A.F. (2025). Predictive Models for Necrotizing Soft Tissue Infections: Are the Available Scores Trustable?. J. Clin. Med., 14.","DOI":"10.3390\/jcm14134550"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Pilarczyk-Zurek, M., Sitkiewicz, I., and Koziel, J. (2022). The Clinical View on Streptococcus anginosus Group\u2014Opportunistic Pathogens Coming Out of Hiding. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.956677"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.21037\/apm-20-2120","article-title":"Streptococcus anginosus group infection as a predictor for the progression of descending necrotizing mediastinitis","volume":"10","author":"Sakai","year":"2021","journal-title":"Ann. Palliat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.cmi.2020.12.018","article-title":"Antibiotic prescribing in patients with COVID-19: Rapid review and meta-analysis","volume":"27","author":"Langford","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pham Dang, N., Delbet-Dupas, C., Mulliez, A., Devoize, L., Dallel, R., and Barthelemy, I. (2020). Five Predictors Affecting the Prognosis of Patients with Severe Odontogenic Infections. Int. J. Environ. Res. Public Health, 17.","DOI":"10.21203\/rs.3.rs-28101\/v1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"tkaf031","DOI":"10.1093\/burnst\/tkaf031","article-title":"Consensus on the Diagnosis and Treatment of Adult Necrotizing Fasciitis (2025 Edition)","volume":"13","author":"Zhou","year":"2025","journal-title":"Burn. Trauma"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5350\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:52:36Z","timestamp":1783533156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":36,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15145350"],"URL":"https:\/\/doi.org\/10.3390\/jcm15145350","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]}}}