Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have ...developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
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•A postmortem bedside surgical procedure was developed for COVID-19 and control patients•Ciliated cells are the main target cell type for SARS-CoV-2 in the respiratory mucosa•Sustentacular cells (non-neuronal) are the main target cell type in the olfactory mucosa•No evidence for infection of olfactory sensory neurons or olfactory bulb parenchyma
Postmortem samples of respiratory and olfactory mucosa and whole olfactory bulbs are harvested immediately after the death of COVID-19 patients revealing ciliated cells and sustentacular cells but not olfactory sensory neurons as the main target cell types for SARS-CoV-2 infection and replication.
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) often requires surgery, but recurrence even after surgery is common. Recurrence rates largely vary in literature and asthma seems to be a ...comorbid factor.
Objective
In this study, we aim to estimate disease recurrence during a long-term follow-up, together with the investigation of possible predicting and/or influencing parameters.
Methods
Out of 196 patients operated for CRSwNP between 01/2000 and 01/2006, 133 patients had a follow-up of at least 10 years and could be included. The inflammatory profile at surgery was determined on nasal tissue and sinonasal secretions, and included analysis of eosinophils, eosinophilic-rich mucus (ERM) typically containing Charcot-Leyden crystals (CLC), and fungal hyphae (FH). During follow-up, recurrence, received treatments and comorbidities were collected.
Results
Out of the 133 included patients, local eosinophilia was present in 81% and ERM in 60%. Recurrence during follow-up was observed in 62%, and was associated with local eosinophilia and ERM (both p < 0.001). Asthma was present in 28% at inclusion, and 17% developed asthma after surgery during follow-up. The presence of asthma, at inclusion as well as developed during follow-up, was significantly associated with recurrence of CRSwNP (p = 0.001 for group comparison).
Conclusion
Recurrence after CRSwNP surgery is common when a long-term follow-up is taken into account. ERM detected in sinonasal secretions at surgery seems to be a predictive factor for recurrence and need for revision surgery. Asthma is a frequently found comorbid factor in CRSwNP, develops even at higher age despite surgical treatment for CRSwNP, and is also associated with a higher recurrence rate. Sustained medical care after surgery is mandatory.
We present a protocol for the rapid postmortem bedside procurement of selected tissue samples using an endoscopic endonasal surgical technique that we adapted from skull base surgery. We describe ...steps for the postmortem collection of blood, cerebrospinal fluid, a nasopharyngeal swab, and tissue samples; the clean-up procedure; and the initial processing and storage of the samples. This protocol was validated with tissue samples procured postmortem from COVID-19 patients and can be applied in another emerging infectious disease.
For complete details on the use and execution of this protocol, please refer to Khan et al. (2021)1 and Khan et al. (2022).2
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•Protocol for postmortem bedside procurement of tissue and non-tissue samples•Endoscopic endonasal surgical technique adapted from skull base surgery•Description of clean-up procedure and initial processing and storage of samples•Protocol validated with tissue samples procured postmortem from COVID-19 patients
Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
We present a protocol for the rapid postmortem bedside procurement of selected tissue samples using an endoscopic endonasal surgical technique that we adapted from skull base surgery. We describe steps for the postmortem collection of blood, cerebrospinal fluid, a nasopharyngeal swab, and tissue samples; the clean-up procedure; and the initial processing and storage of the samples. This protocol was validated with tissue samples procured postmortem from COVID-19 patients and can be applied in another emerging infectious disease.
Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it ...exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.
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•Perineurial olfactory nerve fibroblasts enwrap and protect olfactory axon fascicles•Virions make it in some cases to the leptomeninges covering the olfactory bulb•Absence of evidence for neurotropism and neuroinvasion of several SARS-CoV-2 variants
Khan et al. visualized infected cells, ongoing viral replication, and extracellular virions in postmortem tissue samples of COVID-19 patients who died during an acute phase of infection. They identified anatomical barriers protecting against SARS-CoV-2 neuroinvasion at vulnerable interfaces along the olfactory projection and in the frontal lobe of the brain.
Our aim was to evaluate the long-term objective and subjective results of a modified expansion sphincter pharyngoplasty (ESP) technique in patients with sleep-disordered breathing. Single center ...prospective study of 35 patients underwent an ESP as a primary surgical treatment between June 2012 and September 2015 at the hospital AZ Sint-Jan Bruges-Ostend. Patients were divided into non-OSAS and OSAS (AHI >5). Primary outcome parameters were the Epworth Sleeping Scale (ESS, reduction and score less then 10) and the Visual Analogue Score of snoring (VAS, assessed by partner) evaluated at 3 months and 1 year. In addition, the OSAS group underwent a polysomnography after 6 months to calculate the Apneu-Hypopneu Index (AHI) change. Secondary outcome parameters were possible complications and morbidity rate. The overall Epworth Sleepiness Scale showed a steady total reduction of, respectively, 42 and 48% at the two timepoints. All patients had a post-operative score of less than ten points. The Visual Analogue Score improved in 92% of the patients; of these, the snoring was reduced in 86% and disappeared in 6%. In the OSAS group, we noticed a reduction in AHI of more than 50 in 53% of the patients. A considerable reduction was found in the severe OSAS group, where we found a mean pre-operative average AHI of 41.3/h that was reduced 6 months after the operation to 17.4/h. There were no severe complications or increased morbidity rate observed. This first long-term study shows that the modified ESP seems to be a safe and promising technique in palatal surgery for patients with sleep-disordered breathing. Surgical effectiveness is sustained after 1 year, both in OSAS as in snoring pathology. The technique seems as approachable for the basic ENT surgeon as the uvulopalatopharynoplasty.
The aim of this study was to determine the prevalence and significance of traditional risk factors associated with sensorineural hearing loss (SNHL) in a population of 615 neonates who attended the ...neonatal intensive care unit (NICU) of the University Hospital in Leuven, Belgium between January 2005 and December 2007.
Auditory brainstem response (ABR) audiometry using 40 dB stimuli was performed in all 615 neonates. A retrospective medical database analysis was performed to evaluate the influence of 14 predetermined risk factors. The evaluated risk factors were ototoxic medication, hyperbilirubinemia, in utero infections (including CMV, rubella, syphilis, herpes, and toxoplasmosis), craniofacial anomalies, syndromes associated with SNHL, low birth weight (< 1,500 g), low Apgar score, mechanical ventilation lasting for 5 days or longer, bacterial meningitis, family history of hereditary childhood SNHL, endocranial hemorrhage, hypoxic ischemic encephalopathy, convulsions, and sepsis
Uni- or bilateral hearing impairment was diagnosed in 25 out of 615 neonates (4.1%). In utero infections (especially CMV), craniofacial anomalies, and syndromes known to include SNHL were significant risk factors. For the remaining risk factors, no significant correlation with SNHL was found.
In this study, only in utero infections (especially CMV), craniofacial anomalies, and syndromes known to include SNHL were significant risk factors associated with SNHL. Adequate management of hyperbilirubinemia and ototoxic drug administration may eliminate some of the major historical risk factors associated with SNHL in NICU neonates.
The second European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held on 9-10th November 2017, combined with a ...specific symposium on air pollution and mobile Health technology (mHealth) with the GARD (Global Alliance against Chronic Respiratory Diseases) initiative of WHO (World Health Organization). Physicians from different specialties, researchers, as well as patients and industry representatives from more than 40 countries took part in the Forum. Relevant topics were debated with the aim of allowing the implementation of precision medicine (PM) in daily respiratory care. All debates started with positioning the current state of the art: identification of current gaps in practice, the current consensus and the need for implementation of novel approaches such as endotype-driven treatment, patient empowerment and eHealth tools. This report provides a summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2017, highlighting the research needs in PM, with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key drivers for improving current clinical practice.
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