[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.

An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity.

Activation of the innate immune system via pattern recognition receptors (PRRs) is key to generate lasting adaptive immunity. PRRs detect unique chemical patterns associated with invading microorganisms, but whether and how the physical properties of PRR ligands influence the development of the immune response remains unknown. Through the study of fungal mannans, we show that the physical form of PRR ligands dictates the immune response. Soluble mannans are immunosilent in the periphery but elicit a potent pro-inflammatory response in the draining lymph node (dLN). By modulating the physical form of mannans, we developed a formulation that targets both the periphery and the dLN. When combined with viral glycoprotein antigens, this mannan formulation broadens epitope recognition, elicits potent antigen-specific neutralizing antibodies, and confers protection against viral infections of the lung. Thus, the physical properties of microbial ligands determine the outcome of the immune response and can be harnessed for vaccine development.

Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum.

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.

CT and MRI Findings of Invasive Mucormycosis in the Setting of COVID-19: Experience From a Single Center in India.

An increasing incidence of rhinoorbitocerebral mucormycosis (ROCM) among patients with COVID-19 has recently been reported in India. We report the imaging findings for 25 patients with COVID-19 and invasive ROCM at a single hospital in India. Findings included sinus wall erosions (n = 20), air within bony sinus structures (n = 11), and focal mucosal nonenhancement (n = 8). Orbital, vascular, and intracranial complications were also observed. Radiologists should recognize the increasing incidence of ROCM among patients with COVID-19 to facilitate early diagnosis.

Spectrum of MR imaging findings of sinonasal mucormycosis in post COVID-19 patients.

ADVANCES IN KNOWLEDGE: Radiological findings of mucormycosis in post COVID-19 patients show varied patterns of disease involvement and spectrum of imaging features. One should not solely rely on CT imaging to detect the extent of disease. MRI helps in early and accurate detection of invasion into adjacent structures and so helpful in early intervention.

Computational modeling of nasal nitric oxide flux from the paranasal sinuses: Validation against human experiment.

BACKGROUND: Nitric oxide (NO) is important in respiratory physiology and airway defense. Although the paranasal sinuses are the major source of nasal NO, transport dynamics between the sinuses and nasal cavities are poorly understood. METHODS: Exhaled nasal NO tracings were measured in two non-asthmatic subjects (one with allergic rhinitis, one without) using NO analyzer connected via face mask. We subsequently performed computational fluid dynamics NO emission simulations based on individual CT scans and compared to the experimental data. RESULTS: Simulated exhaled NO tracings match well with experimental data (r > 0.84, p < 0.01) for both subjects, with measured peaks reaching 319.6 ppb in one subject (allergic-rhinitis), and 196.9 ppb in the other. The CFD simulation accurately captured the peak differences, even though the initial sinus NO concentration for both cases was set to the same 9000 ppb based on literature value. Further, the CFD simulation suggests that ethmoid sinuses contributed the most (>67%, other sinuses combined <33%) to total nasal NO emission in both cases and that diffusion contributes more than convective transport. By turning off diffusion (setting NO diffusivity to ~0), the NO emission peaks for both cases were reduced by >70%. CONCLUSION: Historically, nasal NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). Here, we showed that the ethmoid sinuses and diffusive transport dominate the process. These findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.

The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis.

The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders' pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.

Temporal patterns of nasal symptoms in patients with mild severity SARS-CoV-2 infection.

BACKGROUND: No study to date has analyzed the progression of sinonasal symptoms over time in COVID-19 patients. The purpose of this study is to analyze the progression of sinonasal symptoms and risk factors for olfactory dysfunction in the mild severity COVID-19 patient. METHODS: An internet survey was used to assess sinonasal symptoms in patients with COVID-19. Changes in rhinologic domain and symptom-specific Sinonasal Outcome Test (SNOT-22) scores were compared at five time points: two weeks before diagnosis, at diagnosis, two weeks after diagnosis, four weeks after diagnosis, and six months after diagnosis. RESULTS: 521 responses were collected. Rhinologic domain SNOT-22 scores increased significantly (p < 0.001) to 8.94 at the time of diagnosis, remained elevated two weeks post-diagnosis (5.14, p = 0.004), and decreased significantly four weeks post-diagnosis (3.14, p = 0.004). Smell-specific SNOT-22 scores peaked at the time of diagnosis (2.05, p < 0.001), remained elevated two weeks after diagnosis (1.19, p < 0.001), and returned to baseline four weeks post-diagnosis (0.64, p > 0.999). Taste-specific SNOT-22 scores also peaked at diagnosis (2.06, p < 0.001), remained elevated two weeks after diagnosis (1.19, p < 0.001), and returned to baseline four weeks after diagnosis (0.71, p > 0.999). There were no significant differences in sense of smell or taste between 1-month and 6-month timepoints. CONCLUSION: Sinonasal symptoms, particularly loss of smell and taste, may be important presenting symptoms in the mild severity COVID-19 patient. Our findings support incorporating these symptoms into screening protocols. LEVEL OF EVIDENCE: 4.

Reducing the risks of endoscopic sinonasal surgery in the Covid-19 era.

OBJECTIVES: Many routine sinonasal procedures utilising powered instruments are regarded as aerosol-generating. This study aimed to assess how different instrument settings affect detectable droplet spread and patterns of aerosolised droplet spread during simulated sinonasal surgery in order to identify mitigation strategies. DESIGN: Simulation series using three-dimensional (3-D) printed sinonasal model. Fluorescein droplet spread was assessed following microdebriding and drilling of fluorescein-soaked grapes and bones, respectively. SETTING: University dry lab. PARTICIPANTS: 3-D printed sinonasal model. MAIN OUTCOME MEASURES: Patterns of aerosolised droplet spread. RESULTS AND CONCLUSION: There were no observed fluorescein droplets or splatter in the measured surgical field after microdebridement of nasal polyps at aspecific irrigation rate and suction pressure. Activation of the microdebrider in the presence of excess fluid in the nasal cavity (reduced or blocked suction pressure, excessive irrigation fluid or bleeding) resulted in detectable droplet spread. Drilling with either coarse diamond or cutting burs resulted in detectable droplets and greater spread was observed when drilling within the anterior nasal cavity. High-speed drilling is a high-risk AGP but the addition of suction using a third hand technique reduces detectable droplet spread outside the nasal cavity. Using the instrument outside the nasal cavity inadvertently, or when unblocking, produces greater droplet spread and requires more caution.

Radiologic Assessment of the Sinonasal Tract, Nasopharynx and Mastoid Cavity in Patients with SARS-Cov-2 Infection Presenting with Acute Neurological Symptoms.

BACKGROUND: Acute neurological sequela in patients with COVID-19 infection include acute thromboembolic infarcts related to cytokine storm and post infectious immune activation resulting in a prothrombotic state. Radiologic imaging studies of the sinonasal tract and mastoid cavity in patients with COVID-19 infection are sparse and limited to case series. In this report, we investigate the radiologic involvement of nasal cavity, nasopharynx, paranasal sinuses, and mastoid cavity in patients with SARS-CoV-2 infection who presented with acute neurological symptoms. METHODS: Retrospective review of medical records and neuroradiologic imaging in patients diagnosed with acute COVID-19 infection who presented with acute neurological symptoms to assess radiologic prevalence of sinus and mastoid disease and its correlation to upper respiratory tract symptoms. RESULTS: Of the 55 patients, 23 (42%) had partial sinus opacification, with no evidence for complete sinus opacification. The ethmoid sinus was the most commonly affected (16/55 or 29%). An air fluid level was noted in 6/55 (11%) patients, most commonly in the maxillary sinus. Olfactory recess and mastoid opacification were uncommon. There was no evidence of bony destruction in any of the studies, Cough, nasal congestion, rhinorrhea, and sore throat were not significantly associated with any radiological findings. CONCLUSION: In patients who present with acute neurological symptoms, COVID-19 infection is characterized by limited and mild mucosal disease within the sinuses, nasopharynx and mastoid cavity. LEVEL OF EVIDENCE: 4.

The Risk of Spread of Infection During Craniotomy/Craniostomy on Patients with Active Coronavirus Disease 2019 (COVID-19) Infection: Myth or Fact?

OBJECTIVES: Craniotomies/craniostomies have been categorized as aerosol-generating procedures and are presumed to spread coronavirus disease 2019 (COVID-19). However, the presence of severe acute respiratory distress syndrome coronavirus 2 virus in the generated bone dust has never been proved. Our objective is to evaluate the presence of virus in the bone dust (aerosol) generated during emergency neurosurgical procedures performed on patients with active COVID-19. This would determine the true risk of disease transmission during the surgery. METHODS: Ten patients with active COVID-19 infection admitted to our institute in 1 month required emergency craniotomy/craniostomy. The bone dust and mucosal scrapings form paranasal sinuses (if opened) collected during these procedures were tested for the virus using reverse transcription polymerase chain reaction. The entire surgical team was observed for any symptoms related to COVID-19 for 14 days following surgery. RESULTS: Nine patients had moderate viral load in their nasopharyngeal cavity, as detected on reverse transcription polymerase chain reaction. None of the samples of bone dust from these 10 patients tested positive. Mucosal scrapping obtained in 1 patient in which mastoid air cells were inadvertently opened tested negative as well. No health workers from the operating room developed COVID-19-related symptoms. CONCLUSIONS: The bone dust generated during craniotomy/stomy of active patients does not contain the virus. The procedure on an active patient is unlikely to spread the disease. However, a study with larger cohort would be confirmatory.

COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation, and many patients with anosmia show no or only minor respiratory symptoms1. Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 transgenic mice that were originally developed for SARS studies4, we show that infection with SARS-CoV-2 causes severe disease in the lung and, in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions.

Impact of COVID-19 Pandemic on Ambulatory and Operating Room Rhinology Practice in the US.

INTRODUCTION: The pandemic caused by the novel coronavirus virus has altered all facets of clinical practice in the United States. The goal of this study is to better understand the impact of COVID-19 on rhinologic ambulatory and operative practice. METHODS: A 27-item survey to assess these objectives was created and approved by the Division of Rhinology faculty at Rush University Medical Center in April 2020. The survey was then distributed to rhinologists in a web based format via www.surveymonkey.com from April 10 through April 23, 2020. RESULTS: A total of 277 U.S based rhinologists responded to the survey (23.04%). The most common practice types were single specialty private (44.9%) and academic (24.6%). 90.2% practice in a state under a shelter in place order. Comparing pre-COVID baseline to during-COVID, there was statistically significant reduction in the number of patients of seen daily in clinic (p < 0.001). The number of nasal endoscopies in the office and surgical procedures fell dramatically. Overall, 5 respondent rhinologists have been infected with COVID-19 and 27 have been furloughed. CONCLUSION: COVID-19 has drastically affected rhinologic practice. There is a dramatic reduction of in person care in the office setting and surgical management of sinonasal and skull base disease. Enhanced PPE is being used in only half of potentially aerosolizing procedures which represents an area of further education. Novel approaches such as use of virtual encounters and point of care testing should be considered as options to facilitate care.

Quantification of Aerosol Particle Concentrations During Endoscopic Sinonasal Surgery in the Operating Room.

BACKGROUND: Recent indirect evidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission during endoscopic endonasal procedures has highlighted the dearth of knowledge surrounding aerosol generation with these procedures. As we adapt to function in the era of Coronavirus Disease 2019 (COVID-19) a better understanding of how surgical techniques generate potentially infectious aerosolized particles will enhance the safety of operating room (OR) staff and learners. OBJECTIVE: To provide greater understanding of possible SARS-CoV-2 exposure risk during endonasal surgeries by quantifying increases in airborne particle concentrations during endoscopic sinonasal surgery. METHODS: Aerosol concentrations were measured during live-patient endoscopic endonasal surgeries in ORs with an optical particle sizer. Measurements were taken throughout the procedure at six time points: 1) before patient entered the OR, 2) before pre-incision timeout during OR setup, 3) during cold instrumentation with suction, 4) during microdebrider use, 5) during drill use and, 6) at the end of the case prior to extubation. Measurements were taken at three different OR position: surgeon, circulating nurse, and anesthesia provider. RESULTS: Significant increases in airborne particle concentration were measured at the surgeon position with both the microdebrider (p = 0.001) and drill (p = 0.001), but not for cold instrumentation with suction (p = 0.340). Particle concentration did not significantly increase at the anesthesia position or the circulator position with any form of instrumentation. Overall, the surgeon position had a mean increase in particle concentration of 2445 particles/ft3 (95% CI 881 to 3955; p = 0.001) during drill use and 1825 particles/ft3 (95% CI 641 to 3009; p = 0.001) during microdebrider use. CONCLUSION: Drilling and microdebrider use during endonasal surgery in a standard operating room is associated with a significant increase in airborne particle concentrations. Fortunately, this increase in aerosol concentration is localized to the area of the operating surgeon, with no detectable increase in aerosol particles at other OR positions.

Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19.

BACKGROUND: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. OBJECTIVE: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. METHODS: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. RESULTS: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). CONCLUSIONS: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.

Paranasal sinuses computed tomography findings in anosmia of COVID-19.

OBJECTIVE: Olfactory dysfunction in coronavirus disease-2019 (COVID-19) is poorly understood. Thus, mechanistic data are needed to elucidate the pathophysiological drivers of anosmia of COVID-19. METHODS: We performed the current study in patients who presented with anosmia and COVID-19 as documented by the polymerase chain reaction (PCR) assay between April 1st and May 15st, 2020. We assessed for the conductive causes of anosmia with computed tomography (CT) of paranasal sinuses. RESULTS: 49 patients who presented with anosmia and positive PCR assay for COVID-19 were included. The average age was 45 ± 12.2 years. Complete anosmia was present in 85.7% of patients and 91.8% of patients reported sudden onset of olfactory dysfunction. Taste disturbance was common (75.5%). There were no significant pathological changes in the paranasal sinuses on CT scans. Olfactory cleft and ethmoid sinuses appeared normal while in other sinuses, partial opacification was detected only in some cases. CONCLUSION: We did not find significant mucosal changes or olfactory cleft abnormality on CT imaging in patients with anosmia of COVID-19. Conductive causes of anosmia (i.e., mucosal disease) do not seem play a significant role in anosmia of COVID-19.