Clinical and Neuroimaging Characteristics of Ischemic Stroke in Rhino-Orbito-Cerebral Mucormycosis Associated with COVID-19.

PURPOSE: The aim of this study was to compare clinical, neuroimaging, and laboratory features of rhino-orbito-cerebral mucormycosis (ROCM) in COVID-19 patients with and without ischemic stroke complications. METHODS: This observational study was conducted between August and December 2021 and 48 patients who had confirmed ROCM due to COVID-19, according to neuroimaging and histopathology/mycology evidence were included. Brain, orbit and paranasal sinus imaging was performed in all included patients. Data pertaining to clinical, neuroimaging, and laboratory characteristics and risk factors were collected and compared between patients with and without ischemic stroke complications. RESULTS: Of the patients 17 were diagnosed with ischemic stroke. Watershed infarction was the most common pattern (N = 13, 76.4%). Prevalence of conventional risk factors of stroke showed no significant differences between groups (patients with stroke vs. without stroke). Cavernous sinus (p = 0.001, odds ratio, OR = 12.8, 95% confidence interval, CI: 2.3-72) and ICA (p < 0.001, OR = 16.31, 95%CI: 2.91-91.14) involvement was more common in patients with stroke. Internal carotid artery (ICA) size (on the affected side) in patients with ischemic stroke was significantly smaller than in patients without stroke (median = 2.4 mm, interquartile range, IQR: 1.3-4 vs. 3.8 mm, IQR: 3.2-4.3, p = 0.004). Superior ophthalmic vein (SOV) size (on the affected side) in patients with stroke was significantly larger than patients without stroke (2.2 mm, IQR: 1.5-2.5 vs. 1.45 mm IQR: 1.1-1.8, p = 0.019). Involvement of the ethmoid and frontal sinuses were higher in patients with stroke (p = 0.007, OR = 1.85, 95% CI: 1.37-2.49 and p = 0.011, OR = 5, 95% CI: 1.4-18.2, respectively). Patients with stroke had higher D­dimer levels, WBC counts, neutrophil/lymphocyte ratios, and BUN/Cr ratio (all p < 0.05). CONCLUSION: Stroke-related ROCM was not associated with conventional ischemic stroke risk factors. Neuroimaging investigations including qualitative and quantitative parameters of cavernous sinus, ICA and SOV are useful to better understand the mechanism of stroke-related ROCM in COVID-19 patients.

[COVID-19 associated sino-orbital mucormycosis]. / COVID-19-assotsiirovannyi sinoorbital'nyi mukormikoz.

OBJECTIVE: To analyze the dynamics of symptoms in patients with COVID-19 associated sino-orbital mucormycosis. MATERIAL AND METHODS: We describe a series of 13 patients with COVID-19 associated sino-orbital mucormycosis aged 43 to 80 years diagnosed from August to October 2021. All of the patients had a severe disease and required noninvasive ventilation or intubation and administration of dexamethasone. 12 out of 13 patients (92.3%) suffered from diabetes mellitus. Symptoms of fungal infections of the nose and paranasal sinuses appeared in the interval from 7 to 25 days of hospital stay, most often in the second week (from 8 to 12 days). According to clinical and CT features the patients were divided into three groups, combining similar phenotypes of the disease. Group 1 - 1 patient with sinonasal mucormycosis, destruction of the alveolar ridge and the hard palate. Group 2 - 12 patients with sino-orbital mucormycosis. We noted, that in cases of bilateral sinus lesions orbital complications were unilateral in all patients, on the side of more severe lesion. Group 2 was divided into 2 subgroups: subgroup 2a included 2 patients with the superior orbital fissure syndrome: ptosis, proptosis, ophthalmoplegia, periorbital pain, pain or hypoesthesia of half face; subgroup 2b included 10 patients with the orbital apex syndrome, who, in addition to the above symptoms, had loss of vision and conjunctival chemosis. Group 3 - rhino-sino-cerebral mucormycosis. 2 patients from subgroup 2b were transferred to this group due to the intracranial spread of the process and focal neurological symptoms. CONCLUSION: Clinical forms of mucormycosis reflect successive stages of invasive spread of fungi.

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India.

Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

A retrospective clinicopathological analysis of rhino-orbital mucormycosis in second wave of COVID-19.

Background: During the present surge of COVID-19 positive cases, concurrent multifold increase in the incidence of mucormycosis cases has resulted into significant morbidity and mortality. We retrospectively evaluated the clinicopathological features along with microbiological examination findings in histologically diagnosed cases of rhino-orbital mucormycosis. Material and Methods: All the H and E and special stained slides of included mucormycosis cases were retrieved from the records and were evaluated with microbiological findings including screening KOH mount examination and culture results. Results: Out of 16 cases with available details, 10 cases had the previous history of diabetes mellitus. The most frequent single site of involvement was maxillary sinus (7/25) followed by nasal cavity, orbit, ethmoid and sphenoid sinuses. While comparing the histological diagnosis with KOH mount findings and culture results, 15 cases revealed consistent results. Conclusion: A high clinical suspicion, monitoring, early diagnosis, and timely management can improve the morbidity and mortality of this life-threatening complication.

Long-term outcomes of transcutaneous retrobulbar amphotericin B in COVID-19-associated mucormycosis.

Purpose: To describe the long-term outcomes of transcutaneous retrobulbar amphotericin B (TRAMB) in COVID-19-associated mucormycosis. Methods: In total, 18 cases of COVID-19-associated mucormycosis were reviewed. In addition to the recommended treatment protocol, all patients were to be given 3.5 mg/ml/day of TRAMB for five days. Results: Of the 18 patients, 2 presented with stage 3a disease, 13 had stage 3c disease, and 3 patients had central nervous system (CNS) involvement (stage 4a and 4c). In addition to planned retrobulbar doses, five patients were given more while two patients received fewer injections (i.e., <5). At the last mean follow-up of 34.67 (±8.88) weeks, 11 patients were in radiological regression and 4 had stable disease while 2 patients had to undergo exenteration; one mortality was observed because of disease progression. Clinical regression in terms of visual and ptosis improvement was seen in seven and nine patients, respectively. Conclusion: Rhino-orbito-cerebral mucormycosis is a serious condition which warrants an aggressive treatment strategy. In unprecedented situations witnessed recently, TRAMB turned out to be an effective and economical alternative. Though large randomized studies are needed to establish its efficacy, TRAMB still manages to halt progression and salvage the globe in significant number of patients, and hence its use should be encouraged on a case-to-case basis especially in developing countries with limited resources.

Mortality and its determinants after an outbreak of post COVID-19 associated rhino-orbito-cerebral mucormycosis in Central India.

AIM: To report cumulative mortality rates using survival analysis from an outbreak of 211 patients with post COVID-19 rhino-orbito-cerebral mucormycosis (ROCM) in central India. METHODS: Case files of eligible patients were evaluated and mucor was identified from deep nasal swabs using freshly prepared KOH mount. All patients underwent contrast enhanced MRI and disease staging was done based on the extent of anatomical involvement. All patients received intravenous Amphotericin B and sinus debridement was done when possible. Orbital exenteration was reserved for patients with advanced orbital disease. RESULTS: The mean age was 50.7 ± 10.2 of which 147 (70%) were men. At presentation, ROCM was limited to sinuses in 72 (34%), orbital extension was seen in 102 (48%) and 31 (15%) had CNS extension. Sinus debridement was possible in 82% cases (n = 173). Thirty-five (16.6%) patients died due to ROCM. The mean follow-up of patients who survived was 126.6 ± 16.4 days. The cumulative mortality rate at day 10 was 4.8% (95%CI = 2.6-8.8%) and increased 13.1% (95%CI = 9.1-18.7%) at day 30 and to 18.4% (95%CI = 13.6-24.8%) at day 60. Majority of deaths (n = 26, 75%) occurred within 1-month of ROCM presentation. Multivariable hazards analysis showed that patients with CNS involvement had a 6.5 times higher risk of death (Hazard Ratio = 6.71, 95% CI = 2.9-15.5, p < 0.001). CONCLUSION: We report significantly lower mortality rates compared to recent literature that varies from 30 to 80% at 1-month follow-up. Timely sinus debridement and systemic Amphotericin B can help reduce mortality. Presence of CNS extension significantly increased the mortality risk with patients with ROCM.

A cross-sectional study to describe the spectrum of ocular manifestations and risk factors of mucormycosis presenting to a tertiary hospital of East India.

Purpose: To report the clinico-demographic profile of rhino-orbito-cerebral mucormycosis (ROCM) in patients during the "second wave" of the COVID-19 pandemic in eastern India, and their ophthalmic manifestations at presentation to our tertiary institute. Methods: Cross-sectional study amongst patients presenting to our center based on their hospital records. Demographic information, history related to COVID-19, records of detailed ocular examination, and microbiological, radiological, and histopathological investigation were entered into an online worksheet and analyzed using SPSS 26.0. Results: A total of 219 patients with ROCM were treated from May to September 2021, and 110 of these had ocular manifestations at presentation (50.2%). The age of patients ranged from 22 to 83 years and the mean ± standard deviation (SD) age was 49.9 ± 12.9 years. Ninety (81.8%) patients had been diagnosed with diabetes mellitus, 31 (34%) had hypertension, and 10 had other comorbidities. The duration between the onset of COVID-19 and mucormycosis symptoms was 0 to 60 days with a mean ± SD interval of 20.9 ± 12.6 days. Fifty-six (50.9%) patients had a history of steroid use. Unrelenting ocular or facial pain was the most common presenting symptom, ptosis was the most common anterior segment manifestation, and ophthalmic artery occlusion was the most common posterior segment manifestation. Conclusion: Our data from eastern India reinforces the relationship between COVID-19, diabetes, corticosteroid use, and ROCM. Knowledge of various presenting anterior and posterior segment manifestations of the disease as described in the present study will guide clinicians to recognize the disease early and make every effort to prevent complications.

Corneal manifestations and treatment among patients with COVID-19-associated rhino-orbito-cerebral mucormycosis.

Purpose: TO report the corneal manifestations in patients with COVID-19-associated rhino-orbito-cerebral mucormycosis (ROCM). Methods: This study was a retrospective, observational, and record-based analysis of patients of ROCM with corneal involvement. Results: A total of 220 patients were diagnosed with ROCM over a period of 3 months. Thirty-two patients had developed corneal manifestations. The mean age at diagnosis was 52.84 ± 12.8 years. The associated risk factors were systemic mucormycosis, uncontrolled diabetes, recent COVID-19 infection, and injudicious use of systemic steroids. Twenty-nine patients were known diabetics, 32 had recent COVID-19 infection, and 13 gave a history of injudicious use of steroids. The right eye (RE) was affected in nine patients, the left eye (LE) in 20 patients, and both eyes in three patients. Nine patients had a round-oval corneal ulcer. One patient each had a perforated corneal ulcer with uveal prolapse, sealed perforated corneal ulcer, spontaneously healed limbal perforation, diffuse corneal haze with hyphemia, panophthalmitis, diffuse corneal stromal abscess, limbal ischemia, anterior uveitis with posterior synechiae, inferior corneal facet, and filamentary keratitis. Three patients each had a corneal melt and inferior conjunctival xerosis with chemosis. Orbital exenteration was performed in six patients. Five patients with corneal ulcers healed. Topical eye drops of amphotericin (0.5 mg/ml) cycloplegic, antiglaucoma medications, and lubricant eye drops were started along with systemic antifungals. Conclusion: Central corneal ulcer was the most common manifestation of mucormycosis. A concentration as low as 0.5 mg/ml of amphotericin eye drops was effective in the treatment.

Rhino-orbito-cerebral mucormycosis and its resurgence during COVID-19 pandemic: A review.

This study aimed to review the current literature for epidemiology, pathogenesis, clinical spectrum and management of rhino-orbito-cerebral-mucormycosis (ROCM), especially highlighting the association between ROCM and COVID-19 disease and factors resulting in its resurgence during the pandemic. Mucormycosis is a rare, but an important emerging opportunistic fungal infection, often associated with high morbidity and mortality. ROCM is the commonest and also the most aggressive clinical form occurring in debilitated patients in conjunction with sinus or para-sinus involvement due to the propensity for contiguous spread. Recently ROCM has shown an unprecedented resurgence during the current pandemic. Reports from different parts of the world indicated an increased risk and incidence of ROCM in patients who had required hospital admission and have recovered from moderate-to-severe COVID-19 disease. A majority of mucormycosis cases have been reported from India. The presence of diabetes mellitus (DM) and use of corticosteroids for COVID-19 pneumonia were found to be the key risk factors, resulting in higher mortality. Amidst the ongoing pandemic, with the third wave already having affected most of the world, it becomes imperative to adopt a risk-based approach toward COVID-19 patients predisposed to developing ROCM. This could be based on the most recently published literature and emerging data from centers across the world. The present review intended to elucidate the causes that brought about the current spike in ROCM and the importance of its early detection and management to reduce mortality, loss of eye, and the need for mutilating debridement.

Novel treatment of recurrent orbital venolymphatic malformation with sirolimus and rivaroxaban.

Orbital venolymphatic malformations are rare vascular malformations that typically appear early in life and harbor acute and chronic threats to vision. Historically, there are four categories of management: observation, medication, sclerotherapy, and surgery. Currently, there is neither a gold standard for treatment nor randomized control trials comparing treatments.The authors present a 20-year-old male who presented with spontaneous hemorrhage of an orbital venolymphatic malformation occurring with increased frequency and involving more of the posterior orbit. Surgery and sclerotherapy were not feasible options due to the extensive intraorbital and intracranial involvement of the venolymphatic malformation. Systemic steroids treated symptoms but was not curative. To this end, a combination of sirolimus, an mTOR inhibitor, and rivaroxaban, a factor Xa inhibitor, were used to reduce the size of the lesion and minimize the risk of thromboembolic events. This treatment has successfully kept the patient's symptoms in remission for greater than 2 years.

A study of rhino-orbito-cerebral mucormycosis with COVID-19: A new challenge in North West of Rajasthan.

Background: Mucormycosis is a life-threatening fungal disease in immunocompromised patients. There has been increase in the number of mucormycosis associated with COVID-19 patients in second wave. Now country battle with both COVID-19 and mucormycosis. An invasive mucormycosis infection has been a significant burden in India after COVID-19. It has been recently emerged a notifiable disease by the Rajasthan government. Our aim is to develop awareness regarding the importance of early detection and treatment of mucormycosis with COVID-19 and reduce the morbidity and mortality. Materials and Methods: This is a Prospective longitudinal study including 34 patients diagnosed with acute invasive fungal infection by contrast enhancement magnetic resonance imaging studies of paranasal, orbit and brain or nasal biopsy for KOH/culture. Diagnosis is made through routine blood tests, biopsy, and radiological imaging. The patients taken for the study were COVID-19 reverse transcription-polymerase chain reaction positive or recent post COVID-19 (within 15 days) or symptoms of COVID-19 with bilateral pneumonitis. The study was conducted with 34 patients admitted to the department of medicine with mucormycosis within a month may 2021. Results: A total of 34 patients with a mean age of 50.92 years old and male female ratio 24/10 (70.5/29.41) were included in this study. The most common comorbidity was diabetes mellitus (23 patients 67.64%). Nine patients were newly diagnosed or recent onset of diabetes with or after COVID-19 infection. Twenty-four (70.58%) patients were COVID-19 positive or recent (within 15 days) history of COVID-19 positive. Seven (20.58) patients had the history of steroid as a treatment during COVID-19 and 5 (14.70) patients was on oxygen inhalation. One (2.94%) patient was fully vaccinated, and 5 (14.70) patients had the history of steam inhalation. The most common involvement was naso-orbital mucormycosis found in 28 patients (82.35%) followed by nasal-and orbital 26 (76.47) and 18 (52.94), respectively. Naso-Orbito-Cerebral was seen in 16 (47.05) patients. The more common reported symptoms and signs were headache (76.47), facial numbness (64.70), Nasal discharge (52.94), and ophthalmoplegia (52.94). Cranial nerve involvement was seen in 10 patients (facial palsy in 8 patients and bulbar palsy in 2 patients). Total mortality was 7 (7/34 20.58%). Conclusion: COVID-19 infection associated with the wide range of invasive mucormycosis. Early diagnosis and Clinical suspicion of acute invasive fungal sinusitis among COVID-19 patients is essential for better outcomes and higher survival.

Résumé Contexte: La mucormycose est une maladie fongique mortelle chez les patients immunodéprimés. Il y a eu une augmentation du nombre de mucormycose associée aux patients Covid - 19 en deuxième vague. Maintenant, le pays se bat contre le Covid-19 et la mucormycose. Une infection invasive en mucormycose a été une charge significative en Inde après Covid - 19. Il a récemment émergé une maladie notifiable du gouvernement du Rajasthan. Notre objectif est de sensibiliser à l'importance de la détection et du traitement précoce de la mucormycose avec Covid-19 et de réduire la morbidité et la mortalité. Matériaux et méthodes: Il s'agit d'une étude longitudinale prospective comprenant 34 patients diagnostiqués avec une infection fongique invasive aiguë par un contraste d'imagerie magnétique des études d'imagerie par résonance magnétique de biopsie paranasale, en orbite et au cerveau ou nasale pour le KOH / la culture. Le diagnostic est posé par des tests sanguins de routine, une biopsie et une imagerie radiologique. Les patients pris pour l'étude ont été la réaction en chaîne de la transcription inverse de Covid-19, la réaction en chaîne de polymérase positive ou le post-COVID-19 récent (dans les 15 jours) ou les symptômes de Covid-19 avec une pneumonite bilatérale. L'étude a été menée avec 34 patients admis au Département de médecine avec mucormycose dans un mois en mai 2021. Résultats: Un total de 34 patients avec un âge moyen de 50,92 ans et un rapport féminine masculin 24/10 (70,5 / 29,41) ont été inclus dans cette étude. La comorbidité la plus courante était le diabète sucré (23 patients 67,64%). Neuf patients ont été récemment diagnostiqués ou un début récent du diabète avec ou après l'infection à Covid - 19. Vingt-quatre (70,58%) patients étaient des antécédents de Covid - 19 positifs ou récents (dans les 15 jours) de Covid - 19 positifs. Sept (20,58) patients avaient des antécédents de stéroïde comme traitement pendant les patients COVID-19 et 5 (14,70) étaient sous inhalation d'oxygène. Un patient (2,94%) a été entièrement vacciné et 5 (14,70) patients avaient des antécédents d'inhalation de vapeur. L'atteinte la plus courante était la mucormycose naso-orbitale trouvée chez 28 patients (82,35%), suivie respectivement par l'orbital nasal et orbital 26 (76,47) et 18 (52,94). Le naso - orbito-cervebral a été observé chez 16 (47,05) patients. Les symptômes et les signes rapportés les plus courants étaient des maux de tête (76,47), un engourdissement facial (64,70), une décharge nasale (52,94) et une ophtalmoplégie (52,94). Une atteinte du nerf crânien a été observée chez 10 patients (paralysie faciale chez 8 patients et paralysie bulbaire chez 2 patients). La mortalité totale était de 7 (7/34 20,58%). Conclusion: Infection Covid - 19 associée à la large gamme de mucormycose invasive. Le diagnostic précoce et la suspicion clinique de sinusite fongique invasive aiguë chez les patients COVID-19 sont essentiels pour de meilleurs résultats et une survie plus élevée. Mots-clés: Covid - 19, fongique, invasive, nasal, rhinocéros orbital cerebral.

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Decreased mortality in coronavirus disease 2019 associated mucormycosis with aspirin use: a retrospective cohort study.

OBJECTIVE: Rhino-orbito-cerebral mucormycosis is a rapidly progressive disease with high mortality rates of about 60 per cent. The increasing incidence of rhino-orbito-cerebral mucormycosis in coronavirus disease 2019 patients in India and worldwide has become a matter of concern owing to the case fatality rate. This study explored the use of low dose aspirin in decreasing the mortality rate of coronavirus disease 2019 associated mucormycosis. METHOD: This was a retrospective observational study. Patients suffering from post-coronavirus disease 2019 mucormycosis were included in the study. Each patient was treated with surgical debridement and systemic amphotericin B. Low dose aspirin was added, and mortality rates were compared with the patients who did not receive aspirin. RESULTS: The demographic data and rhino-orbito-cerebral mucormycosis staging between the two groups were not significantly different. There was a statistically significant difference in mortality outcomes between the two groups (p = 0.029) and a 1.77 times higher risk of dying for patients not receiving aspirin. Kaplan-Meier survival indicated that patients receiving aspirin had better survival rates (p = 0.04). CONCLUSION: Low dose aspirin improves survival rates in coronavirus disease 2019 associated mucormycosis.

MR imaging spectrum in COVID associated Rhino-Orbito-Cerebral mucormycosis with special emphasis on intracranial disease and impact on patient prognosis.

In the wake of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, a new epidemic of COVID associated mucormycosis (CAM) emerged in India. Early diagnosis and prompt treatment of this deadly disease are of paramount importance in improving patient survival. MRI is the cornerstone of diagnosis of early extrasinus disease, particularly intracranial complications which have traditionally been associated with a high mortality rate. In this review, we depict the sinonasal, perisinus, orbital and intracranial involvement in CAM. Special emphasis is laid on intracranial disease which is categorized into vascular, parenchymal, meningeal, bony involvement and perineural spread. Vascular complications are the most common form of intracranial involvement. Some unusual yet interesting imaging findings such as nerve abscesses involving the optic, trigeminal and mandibular nerves and long segment vasculitis of the internal carotid artery extending till its cervical segment are also illustrated. In our experience, patient outcome in CAM (survival rate of 88.5%) was better compared to the pre-pandemic era. Presence of intracranial disease also did not affect prognosis as poorly as traditionally expected (survival rate of 82.8%). Involvement of brain parenchyma was the only subset of intracranial involvement that was associated with higher mortality (p value 0.016). The aim of this review is to familiarise the reader with the MR imaging spectrum of CAM with special focus on intracranial complications and a brief account of their impact on patient prognosis in our experience.

Coronavirus-associated mucormycosis: different from sinonasal mucormycosis.

OBJECTIVE: To study unusual presentations of coronavirus-associated mucormycosis that are rarely seen in sinonasal mucormycosis cases. METHOD: The data of 400 rhino-orbito-cerebral mucormycosis patients admitted to Sawai Man Singh Hospital, Jaipur, from May 2021 to June 2021, were retrospectively collected. The diagnosis of mucormycosis was made by histological examination of biopsy samples. RESULTS: Out of 400 patients, 62 had symptoms other than common symptoms of rhino-orbito-cerebral mucormycosis. Thirty-four patients had facial palsy, 19 complained of gum ulcers, 6 developed a cheek abscess, 2 complained of maggots in the nose along with common rhino-orbito-cerebral mucormycosis symptoms, and 1 had a cerebellar infarct. CONCLUSION: Mucormycosis is a disease with various presentations, and coronavirus-associated mucormycosis has added unusual presentations to the existing list of manifestations of rhino-orbito-cerebral mucormycosis. In this coronavirus disease era, mucormycosis should always be considered as a diagnosis in patients with these unusual presentations.

Rhino-orbito-cerebral mucormycosis: patient characteristics in pre-COVID-19 and COVID-19 period.

BACKGROUND: Rhino-orbito-cerebral-mucormycosis (ROCM), a rare and potentially fatal disease was seen in increasing numbers during the COVID-19 pandemic. This study describes and compares the patient characteristics and outcomes in COVID-19 associated mucormycosis (CAM) and non-COVID-19 mucormycosis (non-CAM). METHODOLOGY: CAM patients (24 cases) were recruited from the COVID-19 period and non-CAM (24 controls) from the pre-COVID-19 period. Clinical data of the CAM group was collected retrospectively with 3 month outcomes prospectively. The non-CAM group data was collected retrospectively. Patient characteristics were compared and risk factors for mortality in ROCM were assessed. RESULTS: Orbital symptoms [altered vision, restricted eye movements, ptosis] and intracranial involvement were higher in CAM patients on presentation. Similarly, the radiological involvement of orbit (orbital apex, superior orbital fissure) and intracranial cavity (intracranial thrombosis, cavernous sinus) was also higher in CAM patients. Newly detected diabetes was found only in CAM patients (29.2%). Although univariate analysis suggested an increased mortality risk in ROCM patients with orbital involvement, the multivariate analysis showed no increased risk with any of the parameters assessed, including COVID-19 positivity. CONCLUSIONS: Compared to the non-CAM, the disease presentation was severe in CAM with higher frequency of orbital and intracranial involvement. However, with early detection and treatment, the short term survival was comparable in both groups.

Exploring the globe salvaging treatment options in patients of COVID-19-associated mucormycosis with orbital involvement.

Purpose: To explore the various globe salvaging treatment strategies for patients with coronavirus disease 2019-associated mucormycosis (CAM). Methods: This was a prospective: interventional analytical study conducted at a Medical College in rural India. A total of 84 patients of CAM admitted between May 2021 and August 2021 were enrolled for the study. Patients with histologically proven CAM with clinical and/or radiological evidence of orbital involvement were divided into three treatment categories based on the site and extent of the lesion. Re-assessment was performed after 7 days. For patients who worsened with the primary approach, orbital exenteration was considered based on a Sion Hospital Scoring System. A novel approach to intra-orbital anti-fungal therapy, site-centered peri-bulbar injection of amphotericin B (SCPeriAmB), was also explored. All the patients were followed up for at least 3 months. Convenience sampling with descriptive statistics was used. Results: Six patients had to finally undergo exenteration by the end of the study period. The rest of the patients were reported to be stable or improved. No mortalities were reported on delaying the exenteration. No adverse events were noted in patients who were given SCPeriAmB. Conclusion: Globe salvaging treatment options should be advocated as a primary approach in patients with CAM. Site-centered peri-bulbar injections can be considered as an approach for delivering intra-orbital anti-fungal therapy in selected patients.

Uncontrolled diabetes mellitus exacerbated by COVID-19-induced inflammation is the risk factor for COVID-19-associated rhino-orbito-cerebral mucormycosis: A matched pair case-control study.

Purpose: Amidst the ongoing coronavirus disease 2019 (COVID-19) pandemic, India experienced an epidemic of COVID-19-associated rhino-orbito-cerebral mucormycosis (ROCM). This study aimed to describe the epidemiology and elucidate the risk factors for developing COVID-19-associated ROCM, comparing the risk factors among COVID-19 patients with and without ROCM. Methods: This case-control study included all COVID-19-associated ROCM patients treated at our hospital from May 1 to July 30, 2021. Controls included age- and sex-matched COVID-19 patients without ROCM, who were treated during the same time (exact matching, in 1:2 ratio). Matched pair analysis using conditional logistic regression was performed to examine the association of various risk factors with the development of ROCM in COVID-19 patients. Results: The study included 69 patients with COVID-19-associated ROCM and 138 age- and gender-matched controls. Epidemiologically, COVID-19-associated ROCM predominantly affected males (59/69, 85%), in their early 50s (mean 52 years), with 48% (33/69) of patients being from medical resource-constrained settings. On multivariate conditional logistic regression, elevated serum glycated hemoglobin (HbA1c) (odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.03-1.78), blood glucose (OR = 1.008, 95% CI: 1.003-1.013), and C-reactive protein (CRP) (OR = 1.07, 95% CI: 1.02-1.17) were associated with increased odds of developing COVID-19-associated ROCM. Patients with undetected diabetes mellitus with increasing HbA1c (OR = 3.42, 95% CI: 1.30-9.02) and blood glucose (OR = 1.02, 95% CI: 1.005-1.03) (P = 0.02) had a higher probability of developing COVID-19-associated ROCM than patients with established DM. Conclusion: Uncontrolled DM evidenced by elevated HbA1c and blood glucose levels, exacerbated by COVID-19-induced proinflammatory state indicated by elevated CRP, is the principal independent risk factor for COVID-19-associated ROCM. Middle-aged males with undetected DM, from a resource-constraint setting, are particularly at risk.