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.

Optical Coherence Tomography Angiography Parameters of the Retina in SARS-CoV-2 Recovered Subjects.

INTRODUCTION: This study aims to evaluate retinochoroidal optical coherence tomography angiography (OCTA) parameters in patients recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This study was an observational study that included 80 subjects being discharged after having negative reports on the reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 to evaluate OCTA parameters of the retina. The subjects underwent an ophthalmic evaluation that included best-corrected visual acuity (BCVA), intraocular pressure (IOP), color vision (CV), contrast sensitivity (CS), and optical coherence tomography (OCT) parameters. OCTA was done for all patients and was evaluated for foveal avascular zone (FAZ) area, perimeter, and circularity index, and vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), outer retina chorio-capillaries (ORCC), chorio-capillaries (CC), and choroid (C) using 3 x 3 mm scans. The OCTA parameters were compared with normative data of the Indian population for various parameters in question. RESULTS: The subjects included 54/80 (67.5%) males and 26/80 (32.5%) females having a mean age of 52.40 ± 15.71 (18-60) years. The systemic evaluation revealed 38.75% of subjects had hypertension, 30% had diabetes, 20% had kidney disease, 5% had tuberculosis, and 3.75% had coronary artery disease. The mean distance BCVA was logarithm of the minimum angle of resolution (LogMAR) (1.17 ± 0.22), mean IOP was 17.0 ± 4.0 mmHg, mean CS was 2.13 ± 0.36, 50.62% of subjects had normal CV on Farnsworth test while 47% had tritanopia, and none of the subjects had red-green CV defect on Ishihara plates. The OCT scan was normal in 90% of eyes while the posterior vitreous detachment was seen in 4% of eyes, broad vitreomacular adhesion in 2.5% of eyes, and the globally adherent epiretinal membrane was seen in 2.5% of eyes. The mean central macular thickness (CMT) measured 245.14 ± 28.41 micrometers. The mean FAZ area measured 0.37 ± 0.15 mm2, the perimeter was 3.28 ± 1.08 mm, and the circularity index measured 0.41 ± 0.10. The average VD in SCP measured 16.06 ± 12.29, in DCP measured 9.11 ± 8.75, in OR measured 6.38 ± 7.37, in ORCC measured 42.53 ± 12.46, in CC measured 25.83 ± 16.31, and in C measured 25.52 ± 17.49. The VD in coronavirus disease 2019 (COVID-19) subjects was significantly lesser than that in the healthy Indian population in all layers except ORCC. CONCLUSIONS: The SARS-CoV-2 recovered subjects have a reduced VD in retinochoroidal layers from COVID-19, an underlying systemic disease, or both. The CS values fall within normal limits. Several subjects show tritanopia on the Farnsworth test but no red-green CV defect on Ishihara plates.

Ocular sequelae in severe COVID-19 recovered patients of second wave.

Purpose: To evaluate the retinal microvascular changes in patients, recovered from severe COVID-19 during the second wave of the pandemic in North India. Methods: In this observational cross-sectional study, 70 eyes of 35 patients who recovered from severe COVID-19 during the second wave underwent detailed ophthalmic evaluation 4-6 weeks after discharge. Twelve controls were also enrolled, and the difference in the findings between the case and control groups on optical coherence tomography (OCTA) were studied. Result: The ages of study participants ranged from 27 to 60 years with the male:female ratio being 1.05:1. The fundus changes suggestive of ischemia in the form of cotton wool spots and vascular tortuosity were seen in 25 eyes (35.71%). Increased venous tortuosity was the most common finding seen in 23 eyes (32.85%), of which 10 eyes (28.57%) had concurrent hypertensive retinopathy (HTR) changes. There was a significant reduction in the mean vascular density (VD) and perfusion density (PD) for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at inner, outer ring, and whole (P < 0.05). Foveal avascular zone was significantly enlarged in both the SCP (P = 0.01) and the DCP (P = 0.03). The mean ganglion cell-inner plexiform layer (GC-IPL) was significantly reduced in comparison to controls (P < 0.001). Conclusion: Severe COVID-19 can result in microvascular changes at the macula in the form of reduction in vascular and perfusion density, which can be evaluated using OCTA. As structural changes precede functional changes, a close watch is recommended in patients showing compromise in retinal microvasculature.

Bilateral sequential non-arteritic optic neuropathy post-COVID-19.

Corona virus disease 2019 (COVID-19) has been documented to have a spectrum of neuro-ophthalmic manifestations. However, bilateral non-arteritic anterior ischemic optic neuropathy (NAION) post-COVID-19 has not been reported in the literature. We studied the case of a 45-year-old male who presented to our outpatient department (OPD) with bilateral blurring of vision following an episode of COVID-19, 1 month back. Examination and investigations were conclusive of a bilateral NAION. The patient was given a trial of oral steroids. However, the vision loss could not be recovered. Thus, through this case report, we would like to highlight the importance of a close follow-up of patients following COVID-19 infection to detect any sequelae.

Bilevel transportation problem in neutrosophic environment

In the current times of the predominance of COVID-19, almost all the countries are conducting inoculation drives. Given the market’s inability to compute how much to manufacture, how to transport and the frequently changing demand, the cost of safely and timely transporting the vaccines from factory to syringe is currently indeterminate. In this paper, we formulate this situation using a bilevel transportation problem with neutrosophic numbers (BLTP-NN). The problem comes from a vaccine manufacturing company where the vaccine is produced and then transported to different distribution centres from where it is further transported to various health centres for the conduction of their vaccination drive. The authors have tried to perceive this situation from two perspectives by formulating two different problems. The first problem is a bilevel linear fractional transportation problem which aims at minimizing the transportation cost in proportion to per unit maximization of quantity transported. The second problem is a bilevel indefinite quadratic transportation problem which aims at minimizing the transportation cost and depreciation cost. In both problems, cost coefficients are neutrosophic numbers along with availabilities and demands in the constraint set. These formulated bilevel transportation problems in neutrosophic environment are solved using goal programming strategy to arrive at a satisfactory solution. The relevance of this work is to help the decision makers in budgeting their finances related to the transportation by strategic disbursement leading to a smooth administration of vaccination program.

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.

Utility of Antigen-Based Rapid Diagnostic Test for Detection of SARS-CoV-2 Virus in Routine Hospital Settings.

OBJECTIVE: This study aims to evaluate the performance of an antigen-based rapid diagnostic test (RDT) for the detection of the SARS-CoV-2 virus. METHODS: A cross-sectional study was conducted on 677 patients. Two nasopharyngeal swabs and 1 oropharyngeal swab were collected from patients. The RDT was performed onsite by a commercially available immune-chromatographic assay on the nasopharyngeal swab. The nasopharyngeal and oropharyngeal swabs were examined for SARS-CoV-2 RNA by real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay. RESULTS: The overall sensitivity of the SARS-CoV-2 RDT was 34.5% and the specificity was 99.8%. The positive predictive value and negative predictive value of the test were 96.6% and 91.5%, respectively. The detection rate of RDT in RT-qPCR positive results was high (45%) for cycle threshold values <25. CONCLUSION: The utility of RDT is in diagnosing symptomatic patients and may not be particularly suited as a screening tool for patients with low viral load. The low sensitivity of RDT does not qualify its use as a single test in patients who test negative; RT-qPCR continues to be the gold standard test.

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.

Comparative Evaluation of Tears and Nasopharyngeal Swab for SARS-CoV-2 in COVID-19 Dedicated Intensive Care Unit Patients.

Purpose: To compare the cycle threshold (Ct) values of tears and nasopharyngeal (NP) swab in severe COVID-19 ICU patients with positive NP swabs.Procedure: A cross-sectional study for the detection of SARS-CoV-2 by real-time RT-PCR on simultaneously collected NP swabs and tears was performed. Detailed demographic profile, including comorbidities, ocular, and systemic features were analyzed.Results: In the 78 cases, the mean tear positivity was 26.92% (21/78), 2 tear samples being positive despite a negative NP swab. The mean Ct value of tears and NP were 28.17 ± 4.76 and 23.71 ± 6.19, respectively (p= .003). None of the cases had ocular findings or relationship between tear positivity and comorbidity.Conclusions: The viral load of tears is less than the NP secretions with the possibility of prolonged shedding in tears. Tears act as an additional source of contact transmission in ICU that can possibly be decreased by frequent hand hygiene by the patient.Abbreviations: SARS-CoV-2: Severe acute respiratory syndrome coronavirus; RT-PCR: Real-time Reverse transcriptase-polymerase chain reaction; COVID-19: Corona virus disease 2019; ICU: Intensive care unit; RdRp: RNA-dependent RNA polymerase; ORF 1b: Open reading frame 1b; AIIR: Airborne infection isolation room; HCW: Health care workers; VTM: viral transport media; NP: Nasopharyngeal swab; PPE: Personal protective equipment.

Role of Reverse Transcriptase Polymerase Chain Reaction in Cornea Donors During the COVID-19 Pandemic.

PURPOSE: The purpose of this study was to report the analysis of reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal (NP) samples of cornea donors dying because of causes unrelated to severe acute respiratory coronavirus (SARS-CoV-2). METHODS: A retrospective analysis of all cornea donors dying from causes other than SARS-CoV-2 between August 2020 and December 2020 was performed. Informed consent was obtained from the next of kin of the deceased for RT-PCR testing from NP swabs. Rapid antigen testing from all the deceased was performed before in situ cornea excision. In addition, NP samples in viral transport media for RT-PCR were also collected for SARS-CoV-2 analysis. Corneas were released from the eye bank only after a negative RT-PCR report. RESULT: One hundred eighteen corneas from 59 donors were obtained by the eye bank. Eleven donors (18.64%) were positive for SARS-CoV-2 on RT-PCR testing. Six of these 11 donors had a Ct value of E gene less than 25. CONCLUSIONS: NP samples of cornea donors dying due to causes other than coronavirus disease-19 were positive for SARS-CoV-2 on RT-PCR. This implicates that donors could be having asymptomatic/undetected coronavirus disease infection. We recommend adding the routine testing of NP samples of all cornea donors in the eye banking protocol in this ongoing SARS-CoV-2 pandemic.

Evaluation of SARS-CoV-2 in Tears of Patients with Moderate to Severe COVID-19.

PURPOSE: To investigate the presence of SARS-CoV-2 RNA in tears of patients with moderate to severe coronavirus disease 2019 (COVID-19). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with laboratory-proven moderate to severe COVID-19. METHODS: Tears were collected within 48 hours of laboratory confirmation using 3 methods: conjunctival swab plus Schirmer's test strips (group 1), conjunctival swab (group 2), and Schirmer's test strips (group 3). Samples from both the eyes of each patient were transported in a single viral transport media for real-time RT-PCR. Detailed demographic profiles, systemic symptoms, comorbidities, and ocular manifestations were noted. MAIN OUTCOME MEASURES: Viral load of a sample was determined using cycle threshold (Ct) value of E gene. A specimen was considered to show positive results if the amplification curve for the E gene crossed the threshold line within 35 cycles and if it showed positive results on an RNA-dependent RNA polymerase or open reading frame 1b gene assay. RESULTS: Of the 78 patients enrolled in the study, samples from 3 patients were found to be inadequate for analysis. Thirty-six patients (48%) had moderate disease, whereas 39 patients (52%) had severe disease, with no ocular involvement in any patient. In the 75 patients, RT-PCR analysis of tears showed positive results in 18 patients (24%), and 29 of 225 samples (12.9%) showed positive results. Positive results were found in 11 (14.7%), 11 (14.7%), and 7 (9.3%) patients in groups 1, 2, and 3, respectively (P = 0.3105). Mean Ct values in groups 1, 2, and 3 were 28.36 ± 6.15, 29.00 ± 5.58, and 27.86 ± 6.46 (P = 0.92), respectively. Five patients showed positive RT-PCR results by all 3 methods (mean Ct value, 25.24 ± 6.33), and 12 patients showed positive results by any of the 3 methods (mean Ct value, 32.16 ± 1.94), the difference in Ct values being statistically significant (P = 0.029). The median value of symptomatology in patients with positive RT-PCR results from tears was 5 days (range, 4-9 days). CONCLUSIONS: SARS-CoV-2 RNA was detected in tears of 24% of patients with laboratory-proven moderate to severe COVID-19. Conjunctival swab remains the gold standard of tear collection for RT-PCR assay. A significantly higher possibility of viral transmission exists through tears in patients with moderate to severe COVID-19.