NAFAMOSTAT AS NASAL CHEMOPROPHYLAXIS FOR SARS-CoV-2 IN HAMSTERS

Background: Chemoprophylaxis is a critical tool for many infectious diseases, and in COVID-19 may have particular benefit for vulnerable patients that do not maximally benefit from vaccination. Nafamostat inhibits TMPRSS2, which catalyses a critical cell entry pathway for SARS-CoV-2. This study sought to assess efficacy of intranasal nafamostat against airborne transmission of SARSCoV-2 in Syrian Golden hamsters. Method(s): Male hamsters were intranasally administered water or 5 mg/kg nafamostat in water twice daily for 5 days (sentinels). One day after treatment initiation, sentinels were co-housed with an untreated hamster that was intranasally inoculated with 1 x 104 PFU of Wuhan SARS-CoV-2 (donor). Sentinels were separated from the donor by a perforated divider, allowing airflow between zones but not contact. Hamsters were weighed and throat-swabbed throughout. At day 4, all animals were culled, and lung and nasal turbinates were harvested. N-RNA was quantified relative to 18S-RNA by qPCR. A 2-way ANOVA with Bonferroni correction was applied to compare weight changes in the nafamostat group to those in controls. An unpaired t-test was used to compare viral RNA in lung and nasal turbinate between groups. Result(s): SARS-CoV-2 viral RNA was significantly lower in the nasal turbinates of nafamostat-treated hamsters compared to water-treated controls (P = 0.012;Figure 1). Within the lung, SARS-CoV-2 RNA was undetectable in the nafamostat-treated hamsters, but was detectable in the water-treated controls. Viral RNA was undetectable in the swabs of the nafamostat-treated hamsters at all timepoints, but was quantifiable in the water-treated control group from day 3. Body weight of the nafamostat-treated hamsters was significantly lower (P = < 0.001) than in the water-treated animals throughout. SARS-CoV-2 viral RNA was detectable in the donor hamsters lung, nasal turbinate and swab samples confirming validity of the experiment. Conclusion(s): This study demonstrated a protective effect of intranasal nafamostat against airborne SARS-CoV-2 transmission in Syrian golden hamsters. A phase IIa study of intravenously administered nafamostat yielded no evidence of clinical efficacy in hospitalised patients, but further investigation of intranasally administered nafamostat in a prophylactic setting may be warranted.

A PHASE 1B STUDY OF ZOTATIFIN FOR THE TREATMENT OF MILD TO MODERATE COVID (PROpel)

Background: Zotatifin (eFT226) is a potent and selective inhibitor of eukaryotic initiation factor 4A (eIF4A), a host RNA helicase required for SARS-CoV-2 replication. In vitro, zotatifin demonstrates broad spectrum antiviral activity against all human coronaviruses tested. Zotatifin has physicochemical and pharmacokinetic (PK) properties suitable for convenient, single subcutaneous (sc) injection. This study assessed the safety, antiviral activity, and PK of zotatifin in non-hospitalized patients (pts) with mild/moderate COVID. Method(s): PROPEL is a randomized, placebo-controlled, double-blind study in non-hospitalized pts with mild/moderate COVID. At randomization, pts must have had a SARS-CoV-2 positive test within 7 days and at least 1 COVID symptom. Pts were randomized (3:1) to zotatifin or placebo sc in 3 cohorts of 12 pts each. Cohort 1, 2 and 3 received a single dose (SD) of zotatifin of 0.01. 0.02 and 0.035 mg/kg or matching placebo. Safety (adverse event (AE) and laboratory tests), antiviral activity (mid-turbinate nasal swabs and saliva), and plasma PK were collected over 30 days. The primary endpoint was safety;key secondary endpoints included SARS-CoV-2 viral load (VL) and PK. The study was not powered for statistical inferential testing. Result(s): 36 pts were enrolled across all three cohorts and completed a 30-day follow up. Data is currently available for pts in cohorts 1 and 2, 18 and 6 of whom received zotatifin and placebo, respectively. Baseline characteristics were comparable between groups. The most common AE was erythema at injection site in cohort 1 (44%) and cohort 2 (89%), vs. 0% in the zotatifin and pooled placebo groups, respectively. Other AE frequencies were comparable between zotatifin and placebo and no serious AEs were reported. The concentrationtime profile of zotatifin from cohorts 1 and 2 following sc administration was similar to that reported previously following IV administration, demonstrated a terminal elimination half-life (t1/2) of ~ 4 days, high steady-state volume of distribution (Vss) of 31 L/kg, and low plasma clearance (Cl) of 3.9 mL/min/kg. A faster time to viral RNA undetectability was observed with zotatifin vs. placebo (see Fig 1. Not statistically significant). Conclusion(s): Zotatifin was safe, well tolerated and demonstrated a trend in clinical antiviral activity in patients with mild to moderate COVID which supports further clinical development. Zotatifin sc route of administration supports a point of care treatment for COVID.

Comparison of upper and lower airway expression of SARS-COV-2 receptors in mild allergic asthmatics

Background: SARS-CoV-2 virus infects host cells through ACE2 and TMPRSS2 receptors. Protein levels of ACE2 and TMPRSS2 have not been assessed in allergic airways. Method(s): We collected biopsies of endobronchial tissue from steroid-naive mild allergic asthmatics (AA n=23) and non-asthmatic controls (NA n=11), and inferior nasal turbinate tissue from AA with allergic rhinitis (AR n=8) and nonAA/AR controls (NR n=5). Tissue was immune-stained for SARS-CoV-2 receptor ACE2 and surface protein TMPRSS2. The number of immuno-positive cells in epithelium and laminae propria was expressed per mm2 of tissue. Result(s): The number of cells expressing ACE2 was higher in AA endobronchial tissue compared to NA control and AR nasal tissue. TMPRSS2 was higher in AR nasal tissue compared to NR control, and higher in control NA endobronchial tissue versus control NR nasal tissue. Co-expression of ACE2+TMPRSS2 was higher in AA endobronchial tissue versus NA control and trending higher in AR nasal tissue versus NR control (p=0.08). Conclusion(s): Overall, ACE2 is more highly expressed in endobronchial tissue versus nasal tissue, suggesting SARS-CoV-2 may more readily infect lower versus upper airways. It is unknown whether the higher expression of ACE2 and ACE2+TMPRSS2 observed in the airways of mild allergic asthmatic donors versus control donors translates to higher susceptibility to infection.

Nasal swab sampling for antigen test identifies COVID-19 well in all ages

Testing is essential for detecting COVID-19 and differentiating it from other respiratory infections with similar symptoms. We investigated the sampling depth to optimize the COVID-19 diagnostics in a real world decentralized setting. Subjects: 160 randomly selected subjects were included, all visiting medical center either exposed to COVID-19 or as symptomatic. Mean age was 17 years (range 1-79), and 57 subjects were <= 6 years of age. Method(s): Nasopharyngeal (NP) and anterior nasal (NS) specimen were collected from all and a subgroup of PCRor mid-turbinate (>=18 years) samples were included. All COVID-19 positive findings (NP or NS) were assumed to be true positives based on the high specificity of the used automated mariPOC (ArcDia Ltd, Finland) SARS-CoV-2 antigen test (>99.8%). Symptoms, COVID-19 vaccinations and other background information were obtained. Result(s): Detection of 11 possible different respiratory pathogens resulted in 41 NP-positive (26%) and 33 NSpositive (21%) results, of which positive for COVID-19 were 26 NP and 21 NS samples, respectively The best detection rate for COVID-19 was among subjects <=6 years of age, 100% for NS compared with 88% for NP. The negative percent agreement was high among all subjects regardless of symptoms (91-99%), whereas detection rate diminished by the length of sick days of >= 4. Conclusion(s): Anterior nasal specimen from the nostrils shows high potential in detecting COVID-19 in small children with a rapid antigen test. Nasal sampling may decrease the need of COVID-19 testing resources compared to NP swab, thus enabling allocation of resources for more effective infection control.

Rhino-orbital mucormycosis in COVID-19 patients—a new threat?

BackgroundCoronavirus disease 2019 (COVID-19) is known to be associated with a myriad of viral, fungal, and bacterial co-infections. Rhino-orbital mucormycosis is a rare angio-invasive fungal infection which has shown a rising trend in the setting of COVID-19.Case presentationWe describe the imaging findings in 3 cases of rhino-orbital mucormycosis in patients with history of COVID-19. All cases had varying involvement of paranasal sinuses extending into the orbital compartment while case 3 had intracranial extension of infection.ConclusionsRhino-orbital mucormycosis can have aggressive necrosis of the involved paranasal sinuses and orbits with or without cerebral extension. Hence, the correct diagnosis is imperative as prompt antifungal drugs and surgical debridement can significantly reduce mortality and morbidity.

Reduced ACE2 and TMPRSS2 immunopositive bronchial cells in asthmatics after inhaled allergen challenge

Rationale: The incidence of SARS-CoV-2 infection and the impact of corticosteroid treatment in patients with symptomatic airway disease has been a concern. We examined airway expression of SARS-CoV-2 receptors following allergen challenge and steroid intervention in asthmatic patients. Method(s): From steroid-naive mild allergic asthmatic (AA n=23) we collected endobronchial biopsies pre and 24hr post allergen inhalation challenge (AIC). In a subset of AA with allergic rhinitis (AR n=8) we collected inferior nasal turbinate biopsies pre and 24hr post-nasal allergen challenges (NAC) after placebo treatment or after 21 days of 22 mg BID triamcinolone nasal spray. FEV1 and PNIF expressed as % fall from baseline quantified the early (ER, 0-2h) and late (LR, 3-7h) airway responses post challenge. Epithelium and laminae propria were immunostained for ACE2 and TMPRSS2 and expressed as # cells/mm2. Result(s): AIC reduced FEV1 (31% ER, 19% LR) and the number of bronchial cells immunopositive for ACE2, TMPRSS2 and double positive for ACE2/TMPRSS2 (P=0.0002, P=0.04, P=0.02, respectively). The PNIF reduction by NAC (69% ER, 49% LR) was attenuated by triamcinolone (31% ER, 18% LR), but without changes in ACE2 or TMPRSS2 in nasal tissue after NAC or steroid treatment (all P>0.05). In the nasal tissue, significantly fewer cells expressed ACE2 compared to bronchi (P=0.007). Conclusion(s): ACE2 and TMPRSS2 expression in bronchial tissue is reduced in the T2 microenvironment post allergen challenge, however it is unknown if this protects lower airways from SARS-CoV-2 infection. Low expression of ACE2 and TMPRSS2 in nasal tissue made it difficult to determine the effects of NAC or steroid.

Radiological Manifestations of Rhino-Orbito-Cranial Mucormycosis in COVID-19 Patients Correlated With Pathological and Clinical Outcomes and Emphasis on Magnetic Resonance Imaging-Based Scoring System.

There was tremendous increase in the number of cases of mucormycosis among patients affected by coronavirus disease 2019 (COVID-19) during the second wave of pandemic in South Asian countries. This invasive fungal infection primarily affects paranasal sinuses and can have orbito-facial and intracranial extension. We are presenting the radiological findings of invasive mucormycosis with pathological and clinical outcome correlation. It is important for radiologists to have the knowledge of various presentations of this opportunistic infection for early diagnosis and helping clinicians in planning the appropriate line of management. The study also emphasizes on the correlation between the extent of involvement with clinical outcome and we proposed a magnetic resonance imaging (MRI) based scoring system to standardize and prognosticate the patients affected with mucormycosis. MATERIALS AND METHODS: We utilized GE 1.5 tesla, 16-channeled MRI machine for scanning the clinically suspected mucormycosis patients and did plain and contrast study of the paranasal sinuses, orbito-facial study and included brain as and when required. Images were acquired in axial, coronal, and sagittal planes using T1, T2, and fat-saturated short tau inversion recovery sequences (STIR), fat-saturated contrast sequences for better evaluation of the extent of the disease. Diffusion-weighted sequence was also acquired to detect ischemic changes in optic nerve or brain parenchyma. Contrast study was used to detect any major vessel occlusion or cavernous sinus thrombosis in the study population. RESULTS: Total number of cases (n) included in the study were 32. The mean age group was 41-50 years with the median age was 47 years. Out of 32 cases (n=32), in 16 cases (50%) the disease was limited only to the paranasal sinuses and in remaining 16 (50%) cases, disease has spread to other regions such as orbits, facial soft tissues, optic nerve, and brain parenchyma. All the 18 cases with Mild score (MRI ROCM score 1-3) survived and all those with severe score (2 cases) (MRI ROCM score 7-10) did not survive. CONCLUSION: During the second wave of COVID-19 pandemic, we observed a significant rise in acute invasive mucormycosis infection primarily involving the paranasal sinuses and spread to orbito-facial, cerebral parenchyma causing related complications and hence increased morbidity and death. Radiologically, using MRI, it was effectively possible to detect early extrasinonasal spread and other fatal complications thereby guiding the physicians and surgeons in the proper early aggressive management of the disease. Here, we have described the radiological characteristics of paranasal sinus mucormycosis and its spread to other regions. We also proposed an MRI-based Scoring System for standardized assessment of the disease severity. We observed in our study that the extent of disease on MRI is directly correlating with mortality.

Evaluation of a novel anterior nasal swab for the detection of SARS-CoV-2.

BACKGROUND: During the course of the COVID-19 pandemic, nasopharyngeal swabs, combined throat and nose swabs and saliva samples have been evaluated for SARS-CoV-2 detection using nucleic acid amplification tests (NAT). Literature on anterior nasal swabs is limited. We investigated a novel anterior nasal swab that has been designed to standardised self-collection, maximise sample uptake and improve user comfort. We used combined throat and nose swabs and neat saliva samples as the comparators. RESULTS: The overall positive percentage agreement between the Rhinoswab™ and the combined throat and nose swab was 95.2 % at day 2 post participant recruitment and 93.3 % on day 4 post participant recruitment. This was favourable to the positive percentage agreement with saliva at the same time points. CONCLUSION: In our study the Rhinoswab™ performed equally well in comparison to a combined throat and nose swab for the laboratory detection of SARS-CoV-2 using nucleic acid amplification techniques.

Spectrum of magnetic resonance imaging findings in post-COVID-19 patients presenting with rhino-orbito-cerebral mucormycosis in a teaching hospital in Malwa region of Punjab.

Background: Rhino-orbito-cerebral-mucormycosis (ROCM) associated with COVID-19 infection was at its peak during and immediately after the second wave of the pandemic in India during 2021. Many of the risk factors were implicated in the development of this deadly fungal infection, when there was a sudden surge of cases, especially who had a history of COVID-19 infection. Objectives: The objective of the study was to describe the characteristic magnetic resonance imaging (MRI) findings in invasive mucormycosis and to evaluate the extent and severity of invasive mucormycosis. Materials and Methods: A retrospective study was carried out for 4 months which included 60 patients who underwent MRI using a Siemens Avanto 1.5 Tesla scanner. During our study, 68 cases were selected based on clinicoradiological features suspected of ROCM. However, 8 patients were excluded on the basis of exclusion criteria as either there was no definitive evidence of COVID infection or were proven to be negative for mucormycosis on microbiological examination. Results: On the basis of the spectrum of MRI findings, post-COVID-19 related ROCM was broadly categorized into three stages. Out of total of 60 patients, the disease was localized to the nasal and paranasal sinus region (Stage I) in 7 patients (11.66%), extending to adjacent extrasinus orofacial soft tissue structures (Stage II) in 36 patients (60%), and intracranial extension of disease (Stage III) was seen in 17 patients (28.33%). Conclusion: In post-COVID-19 patients presenting with clinical features suspected of ROCM, MRI imaging helps in early diagnosis and staging/severity of ROCM, so that timely intervention can be planned to reduce mortality as well as morbidity.

Environmental and Nasal Pathogen Surveillance in Seattle Area Homeless Shelters

Background. The need for community surveillance of respiratory viruses in high-risk settings such as homeless shelters has been underscored by the COVID-19 pandemic. Here, we show that sampling high-touch surfaces is a low-cost, minimally intensive means of community respiratory virus surveillance. Methods. Environmental samples were collected weekly from adult and family homeless shelters in King County, WA from November 2019 - April 2020. At times when residents were present, a 10cm2 area of selected high-touch surfaces were swabbed and bioaerosol samples were collected in high-traffic areas. Surfaces included entrance and restroom doorknobs, counters, and surfaces unique to each shelter. Study staff collected mid-turbinate swabs from shelter resident participants aged > 3 months with symptoms of acute respiratory illness (ARI). All samples were tested by RT-PCR for 27 viruses. From January 1, 2020 onward, samples were also tested for SARS-CoV-2. Results. A total of 788 environmental swabs, 1509 nasal swabs, and 98 bioaerosol samples from 6 adult and 3 family shelters were tested. Adenovirus (109 positive swabs, 13.8% of tested swabs), rhinovirus (107, 13.6%) and human bocavirus (62, 7.9%) were the most frequently detected viruses in surface swabs. Rhinovirus (160, 10.6%), human coronaviruses (79, 5.24%) and influenza B (43, 2.85%) were the most detected in nasal swabs. All viruses detected in nasal swabs were found in surface swabs. Of 9 surfaces, exterior bathroom doorknobs were the physical location with the highest number of pathogens detected. SARS-CoV-2 was first detected in surface swabs on 3/20/20, and in nasal swabs on 3/10/20. Bioaerosol samples detected virus in a low percentage of samples relative to surface and nasal swabs. Table 1 Count and period prevalence of environmental viral detection by shelter type, November 18, 2019 - April 10, 2020. (Figure Presented) Conclusion. Respiratory viruses detected through environmental sampling in homeless shelters were similar to the viruses detected from ARI episodes in study participants. Environmental surface sampling presents a plausible, minimally invasive method of surveillance for both endemic and emerging respiratory pathogens, as evidenced by the detection of SARS-CoV-2 during the early stages of the pandemic. Further research could focus on sampling public locations for broader community surveillance and culturing viruses found on these surfaces.

Surgical Management of Rhino-Orbito-Cerebral Mucormycosis Post-COVID-19 Infection

Introduction: The pandemic of COVID-19 in association with mucormycosis would be a deadly fungal infection with high level of mortality and morbidity. Our aim is to evaluate the surgical outcome of patients with rhino-orbito-cerebral mucormycosis to suggest better management strategies. Method(s): A total of 62 cases of COVID-19-associated rhino-orbito-cerebral mucormycosis were admitted to the ear, nose, throat department in Mashhad, Iran, from August 1 to October 15, 2021. All data were analyzed using SPSS version 27.0. Descriptive analysis was used for demographic and clinical characteristics. Result(s): Main predisposing conditions were diabetes mellitus (90%) followed by hypertension (41%). Main symptoms were headache (75%), periorbital or retro-orbital pain (61%), visual loss (45%), and facial numbness (41%). Mucosal and ocular findings showed necrosis (67%), blindness (n=35), ptosis (n=31), proptosis (n=27), ophthalmoplegia (n=25), and chemosis (n=20). Neurologic loss of consciousness (19%) and palsies of cranial nerves (53%) were observed. Endoscopy findings showed necrosis (70%), discharge (61%), and crusting (54%). Imaging enhancement revealed mucosal thickening (69%), opacification of sinus (69%), bony destruction of sinus (35%), and orbital involvement (25%). Debridement surgery was necessary in nearly all patients (96%), dominated by ethmoid sinus (90%), maxillary sinus (87%), middle turbinate (80%), and sphenoid sinus (79%). Based on our follow-up, 25 patients died (42%). Those who survived will suffer from no light perception (35%), cranial nerve palsy (12%), and cerebral vascular accident (1.6%). Conclusion(s): Mucormycosis is an aggressive fungal infection. Diabetes mellitus, COVID-19 complication, inappropriate use of corticosteroids, and delayed vaccination had significantly increased its incidence. As there is an urgent need to address this public health concern, we present our data set from Iran.

Turbinate hypertrophy following COVID-19 infection masks choanal atresia in adult.

A 34-year-old female 4 weeks post COVID-19 infection was diagnosed with inferior turbinate hypertrophy and a deviated nasal septum. The patient underwent inferior turbinate bone resection and nasal septoplasty with minimal improvement in nasal obstruction. Upon reevaluation, unilateral choanal atresia was discovered. Subsequent repair of the choanal atresia resolved all complaints of nasal obstruction. This unique presentation of a missed diagnosis of choanal atresia contributes to the idea that a variety of conditions may precede and at times delay the discovery of choanal atresia in adults.

Clinico-radiological Spectrum of COVID-19 Associated Rhino-cerebral Mucormycosis: A Retrospective Cohort Study from a Tertiary Care Hospital

Introduction: Rhino-cerebral Mucormycosis (RCM), in the pre-Coronavirus Disease-2019 (COVID-19) era, was thought to be solely associated with an immunocompromised state. However,anunforeseenoutbreakinthenumberofmucormycosis cases was seen with the increase in Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection. Aim: To study and investigate the clinical characteristics, imaging findings, associated risk factors, and clinical outcomes in COVID-19 associated mucormycosis. Materials and Methods: A retrospective cohort study was conducted comprising 480 cases of COVID-19 associated mucormycosis who presented to the institution between April 2020 and September 2020. The clinical and radiological data were studied and analysed. results: Out of a total of 480 cases, 443 (92.29%) were found to suffering from diabetes mellitus and 392 patients (81.66%) had a history of steroids intake in the studied population. Facial or per orbital swelling followed by pain were the most frequent presenting complaints found in 188 (39.16%) and 162 (33.75%) patients, respectively. Nasal septum and middle turbinate were the most common sites of disease involvement on nasal endoscopic examination. On radiological imaging, maxillary (438;91.25%) was the most commonly involved sinus followed by ethmoids (395;82.29%). Premaxillary/retroantral fat and orbits were the most common sites of extra sinonasal spread of infection found in 278 (57.91%) and 244 (50.83%) patients, respectively. About 238 (49.58%) patients showed bony erosion and dehiscence. Intracranial complications were seen in 73 (15.21%) patients. Glycated Haemoglobin (HbA1c) levels showed significant value with higher disease staging. Oxygen supplementation was frequently associated with extrasinus spread of infection. A total of 44 (9.17%) patients succumbed to death despite aggressive antifungal treatment. conclusion: COVID-19 associated RCM shows frequent and extensive spread to extrasinus regions, especially with uncontrolled diabetes mellitus, steroid administration, and oxygen supplementation. High clinical suspicion, early imaging, and prompt institution of antifungal therapy can aid in reducing mortality rate.

HALO-TRACTION INDUCED OBSTRUCTIVE SLEEP APNEA

Introduction: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. It is a multi-factorial disease with a variety of identified causes including age, male gender, obesity, craniofacial and upper airway abnormalities. We would like to describe a patient who had severe OSA following application of Halo traction, which significantly improved following the removal of the device. Report of Cases: 14-year-old male with medical history of spina bifida, chiari malformation s/p decompression, shunted hydrocephalus and severe scoliosis, was admitted to the hospital for anterior spinal discectomy L2-S1 and Halo application with traction for scoliosis. He previously had nocturnal polysomnogram (NPSG) in 2017 that demonstrated very mild mixed apnea with an apnea hypopnea index (AHI) of 5.5. Because central apneas were very brief and clustered in REM, family elected to repeat a study rather than treat. In 2019, he had a follow up study with complaints of snoring and thirst, and this demonstrated an AHI of 21 with 29 brief central apneas and 72 hypopneas, 1 obstructive apnea. He had a T&A and turbinate ablation and due to the global pandemic did not undergo repeat sleep study. During admission for his anterior spinal discectomy and Halo, he demonstrated persistent night time hypoxia. A split night sleep study showed evidence of severe OSA with pretreatment AHI of 94.4, oxygen nadir 86%. Continuous positive airway pressure (CPAP) was initiated at 5 cm of water and titrated to 11 cm of water. On CPAP of +11 severe obstructive events continued with an AHI of 40.6, oxygen nadir 92%. A bilevel positive airway pressure (BIPAP) titration study the subsequent night started at pressures of 12/6 and titrated to 21/9 with respiratory rate of 12 yet demonstrated AHI of 51, oxygen nadir 89%. Study transitioned to average volume assisted pressure support (AVAPS) with IPAP max of 26, IPAP minimum of 12 EPAP of 9, tidal volume of 175ml, rate of 12 with inadequate control of his obstructive events with an AHI of 24.8, minimum oxygen saturations of 91. While hospitalized, he remained on AVAPS with normal capillary blood gases. Halo traction was removed 2 weeks following his surgery with plan was to send him home on AVAPS and repeat NPSG in 6 weeks. However, as a result of COVID pandemic/Philips recall, CPAP was the only device available for home use, so CPAP therapy at +8 cm was trialed overnight, demonstrating oxygen nadir of 92% and a normal capillary blood gas in the morning. Patient was then discharged home on CPAP of +8 cm of water. He returned back to sleep center for a BIPAP titration study to re-establish BIPAP/AVAPS settings, as his inpatient sleep study had shown severe OSA. During the sleep study, he was started on BIPAP 12/6 and he remained on it throughout the night with 0 central and 0 obstructive events. As he did well, he was advised to continue CPAP +8 with plans to repeat the sleep study off CPAP. In clinic follow up, he reported mild skin breakdown and occasionally waking unrefreshed. Conclusion: As our patient did significantly better following the removal of Halo traction device, it is likely that Halo traction device caused fixed over flexion of the cervical spine that resulted in decrease in his airway diameter, which further worsened during his sleep, and caused severe OSA.

A case series of mucormycosis mimics on MRI-Tales of respite amidst the havoc

Background: Rhinocerebral mucormycosis is new bandit amidst present COVID-19 pandemic, it is an acute and lethal opportunistic fungal infection affecting immunocompromised and diabetic patients. Since the disease has got high morbidity and mortality despite aggressive treatment, radiologists play a very crucial role in early and accurate diagnosis. Erroneous diagnosis should be refrained by logistic approach and thorough clinico-radiological correlation. Material and methods: Ours was a cross sectional study included six cases after taking written informed consent who recently presented with mucormycosis like symptoms and imaging findings during a period of 1 month, but by detailed clinical and radiological evaluation, we concluded that all these cases were either physiological mimics or extraneous artefacts, this helped greatly in relieving undue anxiety of patients and referral physicians and also avoided unnecessary further workup. This study was conducted after approval by the institutional ethical committee. Results: Our study included 3 males and 3 females of age ranging from 32 to 62 years, all of which had history of COVID-positive having mild to moderate CT severity score who were treated with steroids and oxygen therapy (except one case). The most common presenting symptom was headache followed by nasal congestion. The mucor mimickers encountered were benign black turbinate sign, artifacts due to cosmetic dermal fillers and dental fillings, hemangioma, prolonged prone ventilation, and fungal ball. Conclusions: Amidst the sudden spurt in the number of cases of mucormycosis in our country in the present COVID era, there has been an increase in the number of imaging requisitions. This series of cases aims to sensitize radiologists about the importance of detailed clinical history, thorough clinic-radiological correlation and at times also taking extra efforts to reconnect to patients regarding specific clinical history and avoid fallacious diagnosis.

Invasive Fungal Sinusitis During Active COVID-19 Infection.

This case study demonstrates a 58-year-old female who contracted COVID-19 post-vaccination presenting with severe left-sided facial pain, headaches, and dyspnea. A computed tomography was ordered and showed acute sinusitis, and upon bedside endoscopy, the patient was shown to have necrosis of the left-sided middle turbinate with no discoloration, palate necrosis, or facial changes. All samples of the necrotic tissue were reported to be invasive fungal sinusitis. The entire turbinate was resected in the operating room and ethmoid, frontal, and maxillary sinuses were healthy. Chest x-rays post-operatively showed pulmonary effusions and edema although the patient was not stable enough for a lung examination to rule out a pulmonary fungal infection. A bedside endoscopy showed no further necrosis post-operatively although a repeat endoscopy showed duskiness at the lateral attachment of the basal lamella right at the most posterior resection of the middle turbinate. The patient was placed on multiple antifungal agents. The patient remained in hypoxemic respiratory failure and septic shock while on pressors and 2 weeks following this, expired. Post-COVID-19 patients have been shown in the literature to have an increased risk of developing invasive fungal sinusitis (IFS) and all IFS cases during active COVID-19 infection have had a 100% mortality rate.

Nasal and Parotid Blood Pool Activity Is Significantly Correlated with Metabolic Syndrome Components and Sleep Apnea.

Background: Patients with metabolic syndrome components were frequently noted to have increased nasal and parotid activity on clinically referred scintigraphic whole-body blood pool scans. This increase in activity was not observed in patients without metabolic syndrome. Increased nasal blood pool activity in patients with elevated body mass indices (BMIs) has implications for (1) sleep apnea, (2) risk of nasal infection, and (3) possible impaired nasal lymphatic drainage of brain waste proteins. Methods: To follow-up this clinical observation, a retrospective study was performed on 200 patients having whole-body blood pool scans referred over a 3-year period. The whole-body blood pool scans were evaluated for an association between nose and parotid region of interest (ROI) to heart ROI maximum (max) pixel ratios as correlated with clinical conditions, including obesity, diabetes, hypertension, and sleep apnea. Continuous variables of BMI, hemoglobin A1c (HbA1c), blood glucose, and blood lipids were also correlated with these ratios. Results: A direct association of nose to heart max ratio (NHMR) with diabetes, sleep apnea, and hypertension was found with an increase in the ratio of +0.10 (P = 0.002), +0.13 (P = 0.0002), +0.08 (P = 0.0123), respectively. Correlation of NHMR with continuous variables had moderate correlation with BMI (r = 0.36, P < 0.0001), glucose (r = 0.27, P = 0.0001), HbA1c (r = 0.25, P = 0.0008) and less association with the number of diabetes medications (r = 0.22, P = 0.0021). Similar associations were found for parotid to heart max ratios but were weaker than the NHMR. Conclusions: Patients with metabolic syndrome components have significantly increased nasal and parotid activity on blood pool scans. These associations have implications for the treatment of sleep apnea, for nasal infections involving such agents as Covid-19, and for the risk of dementias related to decreased clearance of brain waste proteins through nasal turbinate lymphatics in patients with metabolic syndrome. If further studies support these findings, the nasal turbinates and the increased parasympathetic activity controlling their dilation could become a new therapeutic target.

SARS-CoV-2 PREVALENCE in CHILDREN and ADULTS in 15 US COMMUNITIES: The COMPASS STUDY

Background: There have been few estimates of SARS-CoV-2 seroprevalence in rigorously sampled and geographically broad populations that include children, who have accounted for fewer diagnosed COVID-19 cases compared to adults. The COMPASS study assessed cross-sectional, population-based SARS-CoV-2 seroprevalence and PCR positivity among adults and children in 15 US communities. Methods: Time-location sampling was used to recruit adults and children >2 months of age from randomly selected venues in communities near participating research sites. Demographics, history of COVID-19 and willingness (likely, very likely or already received) to receive an approved COVID-19 vaccine were captured via an interviewer-administered questionnaire. Serologic analysis was performed using a SARS-CoV-2 IgG nucleocapsid antibody (Ab) assay (Abbott Diagnostics, Abbott Park, IL). PCR testing was performed on a mid-turbinate swab using an assay approved by the HPTN Laboratory Center. Prevalence estimates were constructed, overall and by age group (<18 y, 18-39 y, 40-59 y, 60+ y), for each community using survey weights that accounted for the sampling design. Results: A total of 22,732 persons were enrolled (median per community 1,246, range 511 to 2,925) from Jan 2021 to Aug 2021;of these, 2,151 (9.5%) were <18 y. Overall, SARS-CoV-2 seroprevalence (Ab+) ranged from 3.8 to 17.3% (median 12.5%) and SARS-CoV-2 PCR positivity ranged from 0 to 1.9% (median 0.7%). About half of Ab+ and half of PCR+ persons reported no prior or recent (within 14 days) COVID-19 symptoms, respectively [median by community 49.7% (IQR 45.8, 63.9) and 53.6% (IQR 44.3, 58.3)]. Most adults (18+ y) (median 77.3% [69.6 to 92.7%]) reported willingness to get a COVID-19 vaccination;willingness was higher among persons aged 60 y+ [median 88.1%, IQR 83.5, 90.6] compared to those aged 18-39 [median 72.5%, IQR 64.1, 79.8] and 40-59 [median 75.6%, IQR 72.5, 78.4]. The combined prevalence of prior (Ab+) or active (PCR+) SARS-CoV-2 infection across all communities ranged from 4.4 to 17.6% (median 12.7%), and was similar for children (median 12.7%, range 4.4 to 19.7%) and adults (median 12.5%, range 4.4% to 17.8%) among communities enrolling > 25 children (Figure). Conclusion: In this population-based survey, evidence of prior and active SARS-CoV-2 infection varied widely by community but, contrasting with earlier reports, not by age. These findings suggest that acquisition of SARS-CoV-2 is similar across all ages.

A RANDOMIZED CONTROLLED TRIAL of CAMOSTAT in OUTPATIENTS with COVID-19

Background: Camostat, an oral protease inhibitor, blocks entry and replication of SARS-CoV-1 and SARS-CoV-2 in vitro. It is approved for therapy of recurrent pancreatitis in several countries. Camostat has an excellent safety profile and repurposing for COVID-19 treatment was proposed. Methods: We conducted a Phase II randomized, placebo-controlled trial of camostat in adult outpatients with confirmed COVID-19 and one or more risk factors for severe disease (including age ≥65 years, severe obesity, hypertension, diabetes, chronic lung, heart or liver disease). Participants were randomized 2:1 to oral camostat 200 mg or matching placebo four times a day for 14 days. Exclusion criteria were end-stage liver disease, severe renal impairment, oxygen saturation ≤94% on room air, and experimental treatment for COVID-19. The primary efficacy endpoint was hospitalization or death within 28 days. Secondary efficacy included positivity for SARS-CoV-2 by PCR on mid-nasal turbinate swabs on days 7 and 15 compared to baseline. Results: We enrolled 295 participants, 57.3% were female, 15.6% Black and 60% Latinx. Mean age was 51 years (18-93 years). Most (75.3%) were randomized ≤5 days after symptom onset. Common risk factors were hypertension (63.4%), chronic lung disease (33.2%) and diabetes (25.4%), with 46.8% having >1 risk factor. With a lower than anticipated event rate, the primary endpoint of hospitalization or death was not significantly different in the camostat (5.3%, 10/194) and placebo groups (6.1%, 6/99;p=0.78). In the intention-to-treat population, there was a trend towards a lower proportion of PCR positivity in the camostat compared to the placebo group at day 7 (65.2% vs. 75.7%, p=0.12) and day 15 (22.0% vs. 34.3%, p=0.06). Similarly, in a post hoc as treated population, fewer participants in the camostat than in the placebo group remained PCR positive at day 7 (64.7%, 88/136 vs. 76.8%, 53/96;p=0.077) and day 15 (21.8%, 29/133, vs. 34.8%, 23/66;p=0.05). Adverse events occurred in 13% of participants in the placebo and 9% in the camostat group. All severe adverse events (5% in both groups) were related to COVID-19. Conclusion: With a low overall event rate, we did not observe a decrease in risk of hospitalization or death in camostat treated outpatients with COVID-19 at risk for severe disease. SARS-CoV-2 PCR turned negative faster on camostat treatment. Camostat was well tolerated.

Improved oral detection is a characteristic of Omicron infection and has implications for clinical sampling and tissue tropism.

BACKGROUND: The Omicron variant of concern is characterised by more than 50 distinct mutations, most in the spike protein. The implications of these for disease transmission, tissue tropism and diagnostic testing needs study. OBJECTIVES: We evaluated the performance of RT-PCR on saliva (SA) swabs and antigen testing on mid-turbinate MT samples relative to RT-PCR on MT swabs. Patients (n = 453) presenting for outpatient testing at the Groote Schuur Hospital COVID-19 testing centre in Cape Town South Africa were recruited. Participants were recruited during the Delta (n = 304) and Omicron (n = 149) waves. RESULTS: In 30 confirmed Delta infections, positive percent agreement (PPA) of RT-PCR on saliva was only 73% compared to a composite standard of either MT or SA RT-PCR positivity, with rapid decay by day 3 after symptom onset. In contrast, in the 70 Omicron infections, SA performed as well as, or better than, MT samples up to day 5, with an overall PPA of SA swabs of 96% and MT of 93%. A change in antigen test performance was noted, with PPA of 93% in Delta, but only 68% for Omicron. CONCLUSIONS: Altered shedding kinetics appear to be present in Omicron-infected patients with more viral RNA detectable in saliva. Saliva swabs are a promising alternative to nasal samples, especially early in infection when sampling of both sites could improve detection. Lower sensitivity of antigen tests in Omicron is a concern and requires further study.