{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:58:33Z","timestamp":1787169513512,"version":"build-2736575974"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3]]},"abstract":"\n Purpose:<\/jats:title>\n Known predisposing factors for mucormycosis are neutropenia and diabetes. Though COVID-19 is associated with hyperinflammatory response, a high surge in rhino-orbital-cerebral mucormycosis (ROCM) cases was observed during the second wave. The histopathological features reflect the background pathogenesis. This study analyzes the histopathological features and clinical presentation of COVID-19-associated ROCM.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n In this retrospective observational study, the clinical details of 89 proven ROCM patients treated during May\u2013July 2021 were collected from the case records. Histopathological features were correlated with clinical staging groups and outcomes. The mean neutrophil-to-lymphocyte ratio (NLR) of clinical and outcome groups were compared.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The mean age was 54.71 \u00b1 11.03 years, with male patients constituting a majority (78.7%). Uncontrolled diabetes mellitus was noted in 70.8% of patients, and 3.4% had normal range of blood sugar. The mean blood sugar was 298.08 \u00b1 99.51 mg\/dL. The mean duration of onset of symptoms of mucormycosis from the diagnosis of COVID-19 was 17.36 \u00b1 7.392 (3\u201345) days. Poor outcome with disease progression or death occurred in 21.3% of patients. Clinical group II patients (44.9%) with ROCM stages 3c and above had poor outcomes (\n P<\/jats:italic>\n = 0.005). Histopathological analysis showed minimal inflammation in 25.8%, neutrophil extracellular trap (NET) in 75.3%, and angio-invasion in 28.1% of patients. Minimal inflammation was associated with clinical group II (\n P<\/jats:italic>\n = 0.004) and poor outcome (\n P<\/jats:italic>\n = 0.001). Angio-invasion correlated with poor outcome (\n P<\/jats:italic>\n = 0.007). Patients with severe clinical group and poor outcome had higher mean NLR with\n P<\/jats:italic>\n = 0.017 and\n P<\/jats:italic>\n = 0.007, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Vision loss and cerebral involvement had poor outcomes. The histopathologic features such as inflammation and angio-invasion along with NLR aid as prognostic indicators in the management of ROCM. The role of NET in the pathogenesis of COVID-19-associated ROCM needs further studies.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijo.ijo_2366_21","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T08:01:36Z","timestamp":1645776096000},"page":"1013-1018","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["A clinico-pathological study of COVID-19 associated rhino-orbital-cerebral mucormycosis"],"prefix":"10.4103","volume":"70","author":[{"given":"Senthilkumar","family":"Mani","sequence":"first","affiliation":[{"name":"Department of Pathology, Thanjavur Medical College, Thanjavur, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anbuselvi","family":"Thirunavukkarasu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Thanjavur Medical College, Thanjavur, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"B1-20240828","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3390\/microorganisms9030523","article-title":"Epidemiology of mucormycosis in India","volume":"9","author":"Prakash","year":"2021","journal-title":"Microorganisms"},{"key":"B2-20240828","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1086\/432579","article-title":"Epidemiology and outcome of zygomycosis: A review of 929 reported cases","volume":"41","author":"Roden","year":"2005","journal-title":"Clin Infect Dis"},{"key":"B4-20240828","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12281-019-0337-1","article-title":"Mucormycosis: Pathogenesis and pathology","volume":"13","author":"Challa","year":"2019","journal-title":"Curr Fungal Infect Rep"},{"key":"B5-20240828","first-page":"288","article-title":"Pathophysiology of COVID-19: Mechanisms underlying disease severity and progression","volume":"35","author":"Bohn","year":"2020","journal-title":"Physiology (Bethesda)"},{"key":"B6-20240828","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1086\/588660","article-title":"Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group","volume":"46","author":"De Pauw","year":"2008","journal-title":"Clin Infect Dis"},{"key":"B7-20240828","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1128\/CMR.00053-10","article-title":"Histopathologic diagnosis of fungal infections in the 21st century","volume":"24","author":"Guarner","year":"2011","journal-title":"Clin Microbiol Rev"},{"key":"B8-20240828","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4103\/0377-4929.64342","article-title":"Role of histopathology as an aid to prognosis in rhino-orbito-cerebral zygomycosis","volume":"53","author":"Goel","year":"2010","journal-title":"Indian J Pathol Microbiol"},{"key":"B9-20240828","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.3390\/cells9092079","article-title":"On Neutrophil extracellular trap (NET) removal: What we know thus far and why so little","volume":"9","author":"Santocki","year":"2020","journal-title":"Cells"},{"key":"B10-20240828","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.4103\/ijo.IJO_1565_21","article-title":"Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India \u2013 Collaborative OPAI-IJO study on mucormycosis in COVID-19 (COSMIC), Report 1","volume":"69","author":"Sen","year":"2021","journal-title":"Indian J Ophthalmol"},{"key":"B11-20240828","doi-asserted-by":"crossref","first-page":"e1006408","DOI":"10.1371\/journal.ppat.1006408","article-title":"Molecular mechanisms of mucormycosis\u2014 The bitter and the sweet","volume":"13","author":"Baldin","year":"2017","journal-title":"PLoS Pathog"},{"key":"B13-20240828","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4103\/tjosr.tjosr_102_19","article-title":"The clinical pattern of orbital mucormycosis in a tertiary eye care hospital","volume":"58","author":"Prakash","year":"2020","journal-title":"TNOA J Ophthalmic Sci Res"},{"key":"B14-20240828","doi-asserted-by":"crossref","first-page":"944.e9","DOI":"10.1016\/j.cmi.2019.11.021","article-title":"A multicentre observational study on the epidemiology, risk factors, management, and outcomes of mucormycosis in India","volume":"26","author":"Patel","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"B15-20240828","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1080\/01676830.2021.1960382","article-title":"Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients","volume":"40","author":"Nair","year":"2021","journal-title":"Orbit"},{"key":"B16-20240828","doi-asserted-by":"crossref","first-page":"244","DOI":"10.4103\/ijo.IJO_3774_20","article-title":"Mucor in a viral land: A tale of two pathogens","volume":"69","author":"Sen","year":"2021","journal-title":"Indian J Ophthalmol"},{"key":"B17-20240828","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1097\/IOP.0000000000002030","article-title":"Clinical presentations, management and outcomes of rhino-orbital-cerebral mucormycosis (ROCM) following COVID-19: A multi-centric study","volume":"37","author":"Dave","year":"2021","journal-title":"Ophthalmic Plast Reconstr Surg"},{"key":"B18-20240828","doi-asserted-by":"crossref","first-page":"e03582021","DOI":"10.1590\/0037-8682-0358-2021","article-title":"Fatal rhino-orbito-cerebral mucormycosis infection associated with diabetic ketoacidosis post-COVID-19","volume":"54","author":"Bonates","year":"2021","journal-title":"Rev Soc Bras Med Trop"},{"key":"B19-20240828","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.3389\/fimmu.2020.02160","article-title":"Neutrophil-to-lymphocyte ratios are closely associated with the severity and course of non-mild COVID-19","volume":"11","author":"Qun","year":"2020","journal-title":"Front Immunol"},{"key":"B20-20240828","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.18203\/2349-3933.ijam20213196","article-title":"Association of serum interleukin 6 levels with clinical outcome of COVID-19 associated mucormycosis","volume":"8","author":"Sivasankaran","year":"2021","journal-title":"Int J Adv Med"},{"key":"B21-20240828","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12026-020-09145-5","article-title":"COVID-19 as part of the hyperferritinemic syndromes: The role of iron depletion therapy","volume":"68","author":"Perricone","year":"2020","journal-title":"Immunol Res"},{"key":"B22-20240828","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.3390\/cells9061383","article-title":"Neutrophils and neutrophil extracellular traps drive necroinflammation in COVID-19","volume":"9","author":"Tomar","year":"2020","journal-title":"Cells"},{"key":"B23-20240828","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1016\/S2213-2600(20)30216-2","article-title":"COVID-19 cytokine storm: The interplay between inflammation and coagulation","volume":"8","author":"Jose","year":"2020","journal-title":"Lancet Respir Med"},{"key":"B24-20240828","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/nm.3887","article-title":"Diabetes primes neutrophils to undergo NETosis which severely impairs wound healing","volume":"21","author":"Wong","year":"2015","journal-title":"Nat Med"}],"container-title":["Indian Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijo.IJO_2366_21","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:07:36Z","timestamp":1787166456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijo.IJO_2366_21"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.4103\/ijo.ijo_2366_21","relation":{},"ISSN":["0301-4738","1998-3689"],"issn-type":[{"value":"0301-4738","type":"print"},{"value":"1998-3689","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]},"assertion":[{"value":"2021-09-11","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}