A Decade of Clinical Advances in Chronic Rhinosinusitis: 2012-2022.

The field of chronic rhinosinusitis (CRS) is constantly evolving. In the past 10 years, key advancements in basic and translational research as well as clinical studies have improved our understanding and management of CRS. Notably, treatment options have expanded to include novel therapeutic drugs, devices, and surgical techniques. Assessments of patient symptoms and their impact on quality of life have become more standardized. Progress has also been made in both determining the true prevalence of CRS and recognizing comorbidities that can impact CRS severity. Practice guidelines have also shifted from expert opinion to more data-driven analyses. This review highlights major clinical advancements made in the field of CRS over the past 10 years as well as identifies current gaps in knowledge that can form the basis for new areas of study over the next decade.

Correction to: Is diet partly responsible for differences in COVID-19 death rates between and within countries?

[This corrects the article DOI: 10.1186/s13601-020-00323-0.].

Pathophysiology of SARS-CoV-2 Infection of Nasal Respiratory and Olfactory Epithelia and Its Clinical Impact.

PURPOSE OF REVIEW: While the predominant cause for morbidity and mortality with SARS-CoV-2 infection is the lower respiratory tract manifestations of the disease, the effects of SARS-CoV-2 infection on the sinonasal tract have also come to the forefront especially with the increased recognition of olfactory symptom. This review presents a comprehensive summary of the mechanisms of action of the SARS-CoV-2 virus, sinonasal pathophysiology of COVID-19, and the correlation with the clinical and epidemiological impact on olfactory dysfunction. RECENT FINDINGS: ACE2 and TMPRSS2 receptors are key players in the mechanism of infection of SARS-CoV-2. They are present within both the nasal respiratory as well as olfactory epithelia. There are however differences in susceptibility between different groups of individuals, as well as between the different SARS-CoV-2 variants. The sinonasal cavity is an important route for SARS-CoV-2 infection. While the mechanism of infection of SARS-CoV-2 in nasal respiratory and olfactory epithelia is similar, there exist small but significant differences in the susceptibility of these epithelia and consequently clinical manifestations of the disease. Understanding the differences and nuances in sinonasal pathophysiology in COVID-19 would allow the clinician to predict and counsel patients suffering from COVID-19. Future research into molecular pathways and cytokine responses at different stages of infection and different variants of SARS-CoV-2 would evaluate the individual clinical phenotype, prognosis, and possibly response to vaccines and therapeutics.

Chronic Rhinosinusitis and COVID-19.

The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non-type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19.

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2 LEN consensus.

BACKGROUND: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. METHODS: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. RESULTS: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). CONCLUSIONS: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

Clinical-Pathological Correlation of the Pathophysiology and Mechanism of Action of COVID-19 - a Primer for Clinicians.

PURPOSE OF REVIEW: Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease. RECENT FINDINGS: ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge.

Self-reported Taste and Smell Disorders in Patients with COVID-19: Distinct Features in China.

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.

Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19.

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.

Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak?

PURPOSE OF REVIEW: Chemosensory dysfunction in the patients with COVID-19 has been reported frequently in the studies from different regions of the world. However, the prevalence of smell and/or taste disorders presents significant ethnic and geographic variability. In addition, the pathogenesis of chemosensory dysfunction remains unclarified. RECENT FINDINGS: This is a narrative review on the recent state of the prevalence, mechanism, and diagnostic and therapeutic strategy of chemosensory dysfunction in COVID-19 patients during the global pandemic. The chemosensory dysfunction was analysis based on recent studies, which either used questionnaires, Likert scales (0-10), or smell tests to estimate the smell and taste dysfunction. The ethnic and geographic difference of the prevalence of smell and/or taste disorders and the potential underlying mechanisms have been discussed. Several suggestions on the diagnosis and treatment of COVID-19 patients with smell and taste disorders were summarized for the physicians. This review provides a comprehensive overview of the current studies regarding the chemosensory dysfunction during the COVID-19 worldwide outbreak.

EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. A rational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed.

Spices to Control COVID-19 Symptoms: Yes, but Not Only .

There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.

Efficacy of broccoli and glucoraphanin in COVID-19: From hypothesis to proof-of-concept with three experimental clinical cases.

COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 µmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2-interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.

Olfactory Dysfunction in a Mexican Population Outside of COVID-19 Pandemic: Prevalence and Associated Factors (the OLFAMEX Study).

PURPOSE OF REVIEW: To study the prevalence of olfactory loss and its associated factors in a Mexican population a cross-sectional analytical study based on a population interviewed about health, epidemiologic aspects, and sense of smell (tested with four scents: rose, banana, perfume, and gas) was conducted to evaluate olfactory detection, memory, and identification. Levels of sense of smell perception were determined when the participants detected, recognized, or identified all (normosmia), 1-3 (hyposmia), or none (anosmia) of the odorants. Associated factors of olfactory dysfunction were identified by multivariate analysis (odds ratio, 95%CI). RECENT FINDINGS: Olfactory dysfunction is a prevalent disorder affecting up to 20% of the general population. In addition to viral infection, including COVID-19, a number of other causes and factors may also be involved. 1,956 surveys were conducted and 1,921 were analyzed. Most of the participants (62.1%) were women. The general prevalence of olfactory dysfunction, regarding detection, was 7.2% (7.1% hyposmia, 0.1% anosmia). Age-related olfactory deterioration was observed in both sexes from the 5th decade of life (OR 2.74, p = 0.0050). Women showed better olfactory identification (OR 0.73, p = 0.0010). Obesity (OR 1.97, p = 0.0070), low educational level, bad/very bad self-perceived olfactory function (OR 2.74, p = 0.0050), olfactory loss for less than one week (OR 1.35, p = 0.0030), exposure to toxics/irritants (OR 1.31, p = 0.0030), active smoking (OR 1.58, p < 0.0010), and type 2 diabetes mellitus (OR 2.68, 95%CI 1.74-4.10, p < 0.0001) were identified as factors associated with olfactory dysfunction. These results in a Mexican population suggest better olfactory identification (verbalization) in females. Age was a determining factor in the olfactory deterioration process and obesity and diabetes mellitus were also associated with olfactory disorders. Finally, these findings reinforce the differential diagnosis with other potential causes of sense of smell loss, during the COVID-19 outbreak.

Chemosensory dysfunction in COVID-19 out-patients.

BACKGROUND: Since the outbreak in China due to coronavirus disease 2019 (COVID-19) various studies have been published describing olfactory and gustatory dysfunction (OGD). OBJECTIVE: The aim was to investigate the frequency and severity of OGD in SARS-CoV-2 (+) out-patients compared to controls with common cold/flu like symptoms and two negative RT-PCR. METHODS: A multicenter cross-sectional study on SARS-CoV-2-positive out-patients (n = 197) and controls (n = 107) from five Spanish Hospitals. Severity of OGD was categorized by visual analogue scale (VAS). Frequency and severity of the chemosensory impairment were analyzed. RESULTS: The frequencies of smell (70.1%) and taste loss (65%) were significantly higher among COVID-19 subjects than in the controls (20.6% and 19.6%, respectively). Simultaneous OGD was more frequent in the COVID-19 group (61.9% vs 10.3%) and they scored higher in VAS for severity of OGD than controls. In the COVID-19 group, OGD was predominant in young subjects 46.5 ± 14.5 and females (63.5%). Subjects with severe loss of smell were younger (42.7 years old vs 45.5 years old), and recovered later (median = 7, IQR = 5.5 vs median = 4, IQR = 3) than those with mild loss of smell. Subjects with severe loss of taste, recovered later in days (median = 7, IQR = 6 vs median = 2, IQR = 2), compared to those with mild loss. CONCLUSION: OGD is a prevalent symptom in COVID-19 subjects with significant differences compared to controls. It was predominant in young and females subjects. Stratified analysis by the severity of OGD showed that more than 60% of COVID-19 subjects presented a severe OGD who took a longer time to recover compared to those with mild symptoms.