COVID-Associated Sinonasal Mucormycosis: Radiological Pathological Correlation and Prognostic Value of MR Imaging

Purpose  Our aim was to assess the sinonasal magnetic resonance imaging (MRI) features of acute invasive fungal rhinosinusitis (AIFRS) in coronavirus disease (COVID)-associated mucormycosis (CAM) and to correlate these with histopathology and patient outcome in terms of duration of hospital stay and survival at 10 weeks. Methods  Twenty patients with histopathologically confirmed sinonasal CAM underwent MRI (including postcontrast T1-weighted and diffusion-weighted imaging). Histopathological findings (presence of coagulative necrosis, granulomatous reaction, and fungal burden) were recorded and all patients were followed up at 6 and 10 weeks. Statistical analysis was done using chi-square test and Fischer's exact test. Results  Enhancement patterns seen in our subjects included homogeneous, heterogeneous, and lack of contrast enhancement (LOC), with LOC being the most common (65%). Diffusion restriction was found in 90% patients. Statistically significant correlation was found between LOC pattern and presence of coagulative necrosis ( p -value = 0.007), extent of fungal hyphae ( p -value = 0.047), and duration of hospital stay ( p -value = 0.004). Restricted diffusion was also seen to correlate with a high fungal load ( p -value = 0.007). Conclusion  Our study describes the MRI findings of AIFRS in CAM and highlights the imaging features which may be surrogate markers for coagulative necrosis and fungal burden.

COVID-Associated Sinonasal Mucormycosis: Radiological Pathological Correlation and Prognostic Value of MR Imaging.

Purpose Our aim was to assess the sinonasal magnetic resonance imaging (MRI) features of acute invasive fungal rhinosinusitis (AIFRS) in coronavirus disease (COVID)-associated mucormycosis (CAM) and to correlate these with histopathology and patient outcome in terms of duration of hospital stay and survival at 10 weeks. Methods Twenty patients with histopathologically confirmed sinonasal CAM underwent MRI (including postcontrast T1-weighted and diffusion-weighted imaging). Histopathological findings (presence of coagulative necrosis, granulomatous reaction, and fungal burden) were recorded and all patients were followed up at 6 and 10 weeks. Statistical analysis was done using chi-square test and Fischer's exact test. Results Enhancement patterns seen in our subjects included homogeneous, heterogeneous, and lack of contrast enhancement (LOC), with LOC being the most common (65%). Diffusion restriction was found in 90% patients. Statistically significant correlation was found between LOC pattern and presence of coagulative necrosis ( p -value = 0.007), extent of fungal hyphae ( p -value = 0.047), and duration of hospital stay ( p -value = 0.004). Restricted diffusion was also seen to correlate with a high fungal load ( p -value = 0.007). Conclusion Our study describes the MRI findings of AIFRS in CAM and highlights the imaging features which may be surrogate markers for coagulative necrosis and fungal burden.

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.

Effect of Yoga on the Stress, Anxiety, and Depression of COVID-19-Positive Patients: A Quasi-Randomized Controlled Study.

The spread of COVID-19 has resulted in reports of increase in stress, anxiety, and depression across society, especially in people who have tested positive for COVID-19, which affects their mental health and well-being. This article reports a quasi-randomized controlled study conducted in the COVID wards of a hospital to examine the efficacy of add-on yoga intervention in reducing stress, anxiety, and depression in COVID-affected patients under quarantine. The peripheral capillary oxygen saturation level and heart rate of the COVID-19-affected patients were also measured. A total of 62 COVID-19-positive patients participated in the study. The participants were randomized into a control group (n = 31), which received conventional medical treatment alone, and a yoga intervention group (n = 31), which received 50 minutes of yoga intervention along with the conventional medical treatment. Standardized Hospital Anxiety and Depression Scale, Generalized Anxiety Disorder-7 Item, Patient Health Questionnaire-9, and Perceived Stress Scale were administered at the beginning and end of the quarantine period. A significant decrease in stress, anxiety, and depression was observed in the patients who undertook the add-on yoga intervention. There was also a significant decrease in anxiety in the control group, but the intervention group had a larger decrease compared to the control group. Further significant improvements in oxygen saturation and heart rate levels were observed in the group of patients who were practicing yoga, but no significant improvement was observed in the control group. Findings of this study suggest that yoga intervention can be an effective add-on practice in reducing stress, anxiety, and depression levels of COVID-19 patients.

Sensitivity of liquid-based cytology in the diagnosis of mucormycosis in COVID-19 treated patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) infection caused by the novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is associated with a wide range of disease patterns, ranging from mild to life-threatening pneumonia. COVID-19 can be associated with a suppressed immune response and/or hyperinflammatory state due to cytokine storm. Reduced immunity, combined with steroid usage to prevent cytokine storm along with various pre-existing co morbidities can prove to be a fertile ground for various secondary bacterial and fungal infection, including mucormycosis. Diagnosis of mucor is a challenging task given high negativity rate of various detection methods. While histopathology is considered the gold standard, the acquisition of necessary tissue biopsy specimens requires invasive procedures and is time consuming. METHOD: In this study various methods of mucor detection, like conventional cytopathology (CCP), liquid-based cytology (LBC, BD SurepathTM ), potassium hydroxide mount (KOH) preparation, culture and histopathology were analysed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for various methods. RESULTS: This study showed that LBC has sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 72.4%,100%,100% and 38.4% respectively. CONCLUSION: This study showed that, liquid-based cytology (LBC) can be a rapid and effective alternative to histopathology in mucor diagnosis.

CT Imaging Features in Acute Invasive Fungal Rhinosinusitis- Recalling the Oblivion in the COVID Era.

OBJECTIVE: Recent pandemic of COVID19 infection has witnessed a re-emergence of invasive fungal sinusitis especially of the Mucor species, which has been a rare entity in the pre covid era. Covid associated mucormycosis (CAM) is one of the dreaded and fatal complications which has surfaced up and early diagnosis is critical for management and survival .It is identified to affect both subset of patients, those with active COVID-19 infection and those who have recovered from the disease in the last 4-6 weeks. Imaging features suggestive of early invasion with supportive imaging examples and relevance of these findings in clinical decision making is presented. METHODS: This paper reviews the various imaging signs of early invasion in CAM A comprehensive checklist for clinically relevant and quick reporting is also presented. RESULTS: Emphysematous or ulcerative mucosal changes in the nasal cavity is an early imaging feature of CAM. Periantral soft tissue and soft tissue within the pterygopalatine fossa are important imaging signs to indicate extrasinus invasion. Disease within pterygopalatine fossa may lead to multidirectional spread and is an important check site. These findings are seen even in absence of bony erosions owing to the neurovascular spread of disease. Intra orbital and intracranial extensions were found to be fairly common and must be sought for. CONCLUSION: The knowledge of early subtle signs of CAM on imaging can aid in prompt diagnosis of this fatal entity in the pertinent clinical setting. Imaging signs of spread of disease and delineation of its extent as inferred from CT imaging aids in prognosis and appropriate surgical management.

Clinico-Radiological-Pathological Correlation of Visual Loss in COVID-Associated Rhino-Orbito-Cerebral Mucormycosis.

PURPOSE: To correlate the clinical, radiological, and histopathological features in Covid-associated Rhino-orbito-cerebral mucormycosis cases presenting with acute visual loss. DESIGN: Cross-sectional study. METHODS: Covid-associated Rhino-orbito-cerebral mucormycosis cases with unilateral visual loss, planned for exenteration, underwent orbital and ophthalmological ocular examination. The available radiological sequences, doppler ultrasonography and histopathology findings were correlated with clinical manifestations. RESULTS: The median age was 51 years and the male: female ratio was 3:1. All except one presented with unilateral ophthalmoplegia. The ocular media were hazy in 2 eyes. In 8 eyes, retinal changes were suggestive of occlusion of CRA (6), combined occlusion of CRA and central retinal vein (1), and myopic degeneration with hypertensive retinopathy (1). The contralateral eye showed retinal ischemic changes in one patient. Radiological imaging showed orbital apex involvement in the 10 affected eyes and one contralateral eye. Ipsilateral cavernous sinus thrombosis, diffusion restriction on MRI of optic nerve, internal carotid artery narrowing/thrombosis, and cortical watershed infarcts were seen in 8, 4, 4, and 2 cases, respectively. The blood flow in CRA and ophthalmic artery was absent or reduced in all the 10 affected eyes and in 1 contralateral eye. On histopathology, orbital fat necrosis, fungal hyphae, acute inflammation, granuloma formation, ischemic thrombosis of ophthalmic artery was observed in 10 specimens. CRA was patent in 9 and thrombosed in 1 eye. Optic nerve was ischemic in 8 and viable in 2 eyes. CONCLUSION: Acute visual loss in ROCM cases is associated with orbital apex involvement and thrombotic ischemia of ophthalmic artery. Cessation of flow in CRA possibly occurs secondary to ophthalmic artery thrombosis.

Emergence and expansion of highly infectious spike protein D614G mutant SARS-CoV-2 in central India.

COVID-19 has emerged as global pandemic with largest damage to the public health, economy and human psyche.The genome sequence data obtained during the ongoing pandemic are valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating SARS-CoV-2 strains in India will enable the scientific community to understand the emergence of new variants and their impact on human health. The first case of COVID-19 was detected in Chambal region of Madhya Pradesh state in mid of March 2020 followed by multiple introduction events and expansion of cases within next three months. More than 5000 COVID-19 suspected samples referred to Defence Research and Development Establishment, Gwalior, Madhya Pradesh were analyzed during the nation -wide lockdown and unlock period. A total of 136 cases were found positive over a span of three months that included virus introduction to the region and its further spread. Whole genome sequences employing Oxford nanopore technology were generated for 26 SARS-CoV-2 circulating in 10 different districts in Madhya Pradesh state of India. This period witnessed index cases with multiple travel histories responsible for introduction of COVID-19 followed by remarkable expansion of virus. The genome wide substitutions including in important viral proteins were identified. The detailed phylogenetic analysis revealed the circulating SARS-CoV-2 clustered in multiple clades including A2a, A4 and B. The cluster-wise segregation was observed, suggesting multiple introduction links and subsequent evolution of virus in the region. This is the first comprehensive whole genome sequence analysis from central India, which revealed the emergence and evolution of SARS-CoV-2 during thenation-wide lockdown and unlock.

COVID associated mucormycosis: A preliminary study from a dedicated COVID Hospital in Delhi.

BACKGROUND: It is an incontrovertible fact that the Rhino Orbital Cerebral Mucormycosis (ROCM) upsurge is being seen in the context of COVID-19 in India. Briefly presented is evidence that in patients with uncontrolled diabetes, a dysfunctional immune system due to SARS-COV-2 and injudicious use of corticosteroids may be largely responsible for this malady. OBJECTIVE: To find the possible impact of COVID 19 infection and various co-morbidities on occurrence of ROCM and demonstrate the outcome based on medical and surgical interventions. METHODOLOGY: Prospective longitudinal study included patients diagnosed with acute invasive fungal rhinosinusitis after a recent COVID-19 infection. Diagnostic nasal endoscopy (DNE) was performed on each patient and swabs were taken and sent for fungal KOH staining and microscopy. Medical management included Injection Liposomal Amphotericin B, Posaconazole and Voriconazole. Surgical treatment was restricted to patients with RT PCR negative results for COVID-19. Endoscopic, open, and combined approaches were utilized to eradicate infection. Follow-up for survived patients was maintained regularly for the first postoperative month. RESULTS: Out of total 131 patients, 111 patients had prior history of SARS COVID 19 infection, confirmed with a positive RT-PCR report and the rest 20 patients had no such history. Steroids were received as a part of treatment in 67 patients infected with COVID 19. Among 131 patients, 124 recovered, 1 worsened and 6 died. Out of 101 known diabetics, 98 recovered and 3 had fatal outcomes. 7 patients with previous history of COVID infection did not have any evidence of Diabetes mellitus, steroid intake or any other comorbidity. CONCLUSION: It can be concluded that ROCM upsurge seen in the context of COVID-19 in India was mainly seen in patients with uncontrolled diabetes, a dysfunctional immune system due to SARS-COV-2 infection and injudicious use of corticosteroids.

Rhino-Orbito-Cerebral-Mucormycosis During the COVID-19 Second Wave in 2021 - A Preliminary Report from a Single Hospital.

PURPOSE: To list the clinico-epidemiological profile and possible risk factors of COVID-19 associated rhino-orbital-cerebral mucormycosis (CA-ROCM) patients presenting to a COVID dedicated hospital during the second wave of COVID-19 in India. PATIENTS AND METHODS: A cross-sectional, single-center study was done on 60 cases of probable CA-ROCM based on clinical features and supportive diagnostic nasal endoscopic findings and/or radiologic findings. Patients with recent or active COVID-19 were included. The demographic profile, clinical features, possible risk factors and diagnostic workup (microbiological, pathological and radiological) were analysed to identify the triggering factors for CA-ROCM. RESULTS: The age of patients ranged from 29 to 75 years and male-female ratio was 3:1. The duration between the first positive COVID report and onset of CA-ROCM was 0 to 47 days. Forty-nine (81.66%) patients had a recent COVID infection and 11 (18.33%) had active COVID infection at presentation. Thirty-five patients (58%) had ocular/orbital involvement at presentation. In the affected eye, 10 had no perception of light and in the rest visual acuity ranged from log MAR 0 to +1.5. Ocular manifestations were ptosis (29), ophthalmoplegia (23), periocular tenderness and edema (33), proptosis (14), black discoloration of eyelids (3), facial palsy (3), endophthalmitis (4), retinal artery occlusion (8), disc edema (4) and disc pallor (5). Twenty-two (25%) patients had neither received steroids nor oxygen. Thirty patients (50%) were managed with oxygen while 38 patients (63.3%) with systemic steroids. The most common risk factor was diabetes in 59 patients. The average glycosylated hemoglobin (HbA1c) was 10.31 ± 2.59%. Systemic Amphotericin B was started in all the patients. Radical surgical debridement was performed in 12 patients and the remaining were planned. CONCLUSION: SARS-CoV-2 variant with accompanying glycaemic dysregulation was found to be the triggering factor for the epidemic of CA-ROCM.

A meta-analysis of SARS-CoV-2 patients identifies the combinatorial significance of D-dimer, C-reactive protein, lymphocyte, and neutrophil values as a predictor of disease severity.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to be the causative agent of COVID-19, has led to a worldwide pandemic. At presentation, individual clinical laboratory blood values, such as lymphocyte counts or C-reactive protein (CRP) levels, may be abnormal and associated with disease severity. However, combinatorial interpretation of these laboratory blood values, in the context of COVID-19, remains a challenge. METHODS: To assess the significance of multiple laboratory blood values in patients with SARS-CoV-2 and develop a COVID-19 predictive equation, we conducted a literature search using PubMed to seek articles that included defined laboratory data points along with clinical disease progression. We identified 9846 papers, selecting primary studies with at least 20 patients for univariate analysis to identify clinical variables predicting nonsevere and severe COVID-19 cases. Multiple regression analysis was performed on a training set of patient studies to generate severity predictor equations, and subsequently tested on a validation cohort of 151 patients who had a median duration of observation of 14 days. RESULTS: Two COVID-19 predictive equations were generated: one using four variables (CRP, D-dimer levels, lymphocyte count, and neutrophil count), and another using three variables (CRP, lymphocyte count, and neutrophil count). In adult and pediatric populations, the predictive equations exhibited high specificity, sensitivity, positive predictive values, and negative predictive values. CONCLUSION: Using the generated equations, the outcomes of COVID-19 patients can be predicted using commonly obtained clinical laboratory data. These predictive equations may inform future studies evaluating the long-term follow-up of COVID-19 patients.