Mucosal antibody response and SARS-CoV-2 shedding in patients with COVID-19 related olfactory dysfunction.

Olfactory dysfunction (OD) was one of the most common symptom of infection with the Wuhan strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and could persist for several months after symptom onset. The pathogenesis of prolonged OD remains poorly understood but probably involves sustained viral replication associated with limited mucosal immune response to the virus. This prospective study was conducted to investigate the potential relationship between nasal SARS-CoV-2 viral load and antibody levels in patients with loss of smell. One hundred and five patients were recruited 2 weeks after presenting with confirmed coronavirus disease 2019 associated OD. Based on the identification sniffing test performed at enrollment, 52 patients were still anosmic or hyposmic and 53 were normosmic. SARS-CoV-2 was detectable in nasal wash of about 50% of anosmic and normosmic patients. Higher viral load was detected in anosmic patients with lower levels of SARS-CoV-2 specific nasal immunoglobulins (Ig) IgG and IgA. This association was not observed in normosmic patients. No relationship between nasal viral load and antibodies to endemic coronaviruses was observed. SARS-CoV-2 replication in the nasal cavity may be promoted by defective mucosal antibody responses in patients with OD. Boosting mucosal immunity may limit nasal SARS-CoV-2 replication and thereby help in the control of persistent OD.

ATP1A1 is a promising new target for melanoma treatment and can be inhibited by its physiological ligand bufalin to restore targeted therapy efficacy.

Despite advancements in treating metastatic melanoma, many patients exhibit resistance to targeted therapies. Our study focuses on ATP1A1, a sodium pump subunit associated with cancer development. We aimed to assess ATP1A1 prognostic value in melanoma patients and examine the impact of its ligand, bufalin, on melanoma cell lines in vitro and in vivo. High ATP1A1 expression (IHC) correlated with reduced overall survival in melanoma patients. Resistance to BRAF inhibitor was linked to elevated ATP1A1 levels in patient biopsies (IHC, qPCR) and cell lines (Western blot, qPCR). Additionally, high ATP1A1 mRNA expression positively correlated with differentiation/pigmentation markers based on data from The Cancer Genome Atlas (TCGA) databases and Verfaillie proliferative gene signature analysis. Bufalin specifically targeted ATP1A1 in caveolae, (proximity ligation assay) and influenced Src phosphorylation (Western blot), thereby disrupting multiple signaling pathways (phosphokinase array). In vitro, bufalin induced apoptosis in melanoma cell lines by acting on ATP1A1 (siRNA experiments) and, in vivo, significantly impeded melanoma growth using a nude mouse xenograft model with continuous bufalin delivery via an osmotic pump. In conclusion, our study demonstrates that ATP1A1 could serve as a prognostic marker for patient survival and a predictive marker for response to BRAF inhibitor therapy. By targeting ATP1A1, bufalin inhibited cell proliferation, induced apoptosis in vitro, and effectively suppressed tumor development in mice. Thus, our findings strongly support ATP1A1 as a promising therapeutic target, with bufalin as a potential agent to disrupt its tumor-promoting activity.

Effectiveness of platelet-rich plasma in long-lasting post-viral olfactory dysfunction: a case-series.

OBJECTIVE: To investigate the platelet-rich plasma (PRP) effectiveness in patients with a long-lasting postviral olfactory dysfunction (LPOD). METHODS: Forty-three consecutive patients with a long-lasting postviral OD were prospectively recruited. The injection of 1 mL of PRP was carried out in both olfactory clefts. The pre- to 6-month post-PRP injection change in olfaction was assessed with the olfactory disorder questionnaire (ODQ) and the threshold, discrimination, and identification (TDI) tests. RESULTS: Forty-three patients received bilateral PRP injections (24 females). The mean age of patients was 58.9 ± 16.8 years. The mean duration of LPOD was 8.7 years. The pre to 6-month post-injection mean TDI significantly improved from 10.3 ± 10.2 to 20.12 ± 12.07 (p = 0.001). The mean ODQ significantly decreased from 29.8 ± 13.0 to 23.4 ± 11.3 (p = 0.013). The average change of the TDI and the ODQ were 9.8 and 6.4, respectively. Age was inversely associated with the 6-month threshold score. CONCLUSION: PRP appears to be a promising therapeutic strategy for long-lasting postviral OD. Our findings support the conduction of controlled randomized trial in this population of patients.

Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study.

OBJECTIVE: To investigate the prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients 24 months after the infection. METHODS: From 22 March 2020 to 5 June 2022, 251 COVID-19 patients were followed in three European medical centres. Olfactory function was assessed with subjective patient-reported outcome questionnaires and odour identification tests at baseline, 6, 12, 18 and 24 months postinfection. The predictive values of epidemiological and clinical data were investigated with multivariate analysis. RESULTS: One hundred and seventy-one patients completed the evaluations. The odour identification test revealed that 123 patients (50.8%) had OD at baseline. The prevalence of persistent psychophysical abnormalities at 6, 12, 18 and 24 months post-COVID-19 was 24.2%, 17.9%, 5.8% and 2.9%, respectively (p = 0.001). Parosmia occurred in 40 patients (23.4%) and lasted 60 ± 119 days. At 2 years, 51 patients (29.8%) self reported that their olfaction was unnormalised. Older patients had better odour identification evaluations at baseline (p < 0.001) but those with OD reported lower odour identification test scores at the end of the follow-up. Parosmia occurred more frequently in young patients. The olfactory training was significantly associated with higher values of Sniffin' Sticks tests at 18 months postinfection (rs = 0.678; p < 0.001). CONCLUSION: Two years post-COVID-19, 29.8% of patients reported persistent OD, but only 2.9% had abnormal identification psychophysical evaluations.

Effectiveness of olfactory training in COVID-19 patients with olfactory dysfunction: a prospective study.

OBJECTIVES: To investigate effectiveness of olfactory training (OT) in COVID-19 patients with persistent olfactory dysfunction (OD). METHODS: From March 2020 to March 2022, COVID-19 patients with OD were prospectively followed in three European medical centers for a period of 18 months. A standardized OT protocol were recommended to patients. Patient-reported outcome questionnaires and psychophysical evaluations were used to evaluate olfaction at baseline, 6, 12, and 18 months after the start of OT. The evolution of olfactory outcome was compared according to the adherence to the OT protocol. RESULTS: Fifty-seven patients completed the evaluations. Thirty-two patients fully adhered to the OT, while 25 did not adhere. The psychophysical scores significantly improved from baseline to 6-month post-infection in both groups. In the OT group, the psychophysical scores continued to significantly improve from 6 to 12 months after the start of OT (p = 0.032). The mean duration of OT was 15.4 weeks. The mean delay of patient recovery perception was comparable between groups (27.4 weeks). The occurrence of cacosmia (35.1%) and parosmia (43.9%) throughout the follow-up period was comparable between groups. There proportion of phantosmia was higher in training (34.4%) compared with no-OT (16.0%; p = 0.007) group. The baseline Sniffin'Sticks tests was positively associated with the 6-month Sniffin'Sticks tests (rs = 0.685; p < 0.001) and negatively associated with the time of recovery (rs = - 0.369; p = 0.034). CONCLUSIONS: The adherence to an OT protocol was associated with better mid-term improvement of psychophysical scores. Future large-cohort randomized-controlled studies are needed to confirm the effectiveness of OT in COVID-19 patients.

Platelet-rich plasma injection in the olfactory clefts of COVID-19 patients with long-term olfactory dysfunction.

OBJECTIVE: To investigate safety, feasibility, and effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of COVID-19 patients with persistent olfactory dysfunction (OD). METHODS: From March 2022 to July 2022, COVID-19 patients with persistent OD were consecutively recruited to benefit from PRP injection into the olfactory clefts. Patient pain, annoyance, time of procedure, and adverse events were evaluated. Olfactory function was evaluated at baseline and 2-month post-injection with the olfactory disorder questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. RESULTS: Eighty-seven patients with anosmia (N = 30), hyposmia (N = 40), or parosmia (N = 17) with a mean OD duration of 15.7 months completed the evaluations. The PRP injection was successfully performed in all patients with a mean procedure time of 18.4 ± 3.4 min. The adverse events included transient epistaxis (N = 31), parosmia related to xylocaine spray (N = 10), and vasovagal episode (N = 2). The injection procedure was evaluated as somewhat or moderately painful by 41 (47%) and 22 (25%) patients, respectively. Thirty-seven patients were assessed after 2 months post-injection. The mean ODQ and TDI scores significantly improved from baseline to 2-month post-injection (p < 0.01). The olfactory improvement occurred after a mean of 3.6 ± 1.9 weeks. CONCLUSION: The injection of PRP into the olfactory clefts is safe and associated with adequate patient-reported outcomes. The findings of this preliminary study suggest possible efficacy on subjective and psychophysical evaluations, but future randomized controlled studies are needed to determine the superiority of PRP injection over placebo.

Usefulness, acceptation and feasibility of electronic medical history tool in reflux disease.

OBJECTIVES: To investigate usefulness, feasibility, and patient satisfaction of an electronic pre-consultation medical history tool (EPMH) in laryngopharyngeal reflux (LPR) work-up. METHODS: Seventy-five patients with LPR were invited to complete electronic medical history assessment prior to laryngology consultation. EPMH collected the following parameters: demographic and epidemiological data, medication, medical and surgical histories, diet habits, stress and symptom findings. Stress and symptoms were assessed with perceived stress scale and reflux symptom score. Duration of consultation, acceptance, and satisfaction of patients (feasibility, usefulness, effectiveness, understanding of questions) were evaluated through a 9-item patient-reported outcome questionnaire. RESULTS: Seventy patients completed the evaluation (93% participation rate). The mean age of cohort was 51.2 ± 15.6 years old. There were 35 females and 35 males. Patients who refused to participate (N = 5) were > 65 years old. The consultation duration was significantly lower in patients who used the EPMH (11.3 ± 2.7 min) compared with a control group (18.1 ± 5.1 min; p = 0.001). Ninety percent of patients were satisfied about EPMH easiness and usefulness, while 97.1% thought that EPMH may improve the disease management. Patients would recommend similar approach for otolaryngological or other specialty consultations in 98.6% and 92.8% of cases, respectively. CONCLUSION: The use of EPMH is associated with adequate usefulness, feasibility, and satisfaction outcomes in patients with LPR. This software is a preliminary step in the development of an AI-based diagnostic decision support tool to help laryngologists in their daily practice. Future randomized controlled studies are needed to investigate the gain of similar approaches on the traditional consultation format.

Comparison of prevalence and evolution of COVID-19 olfactory disorders in patients infected by D614 (wild) and B.1.1.7. Alpha variant: a brief report.

OBJECTIVES: To investigate the prevalence and the evolution of olfactory disorders (OD) related to coronavirus disease 2019 (COVID-19) in patients infected during the first and the second European waves. METHODS: From March 2020 to October 2020, COVID-19 patients with OD were recruited and followed over the 12-month post-infection. The following data were collected: demographic, treatments, vaccination status, and olfactory function. Olfaction was assessed with the Olfactory Disorder Questionnaire (ODQ), and threshold, discrimination, and identification (TDI) test. Outcomes were compared between patients of the first wave (group 1: wild/D614G virus) and the second wave (group 2: B.1.1.7. Alpha variant) at 1-, 3- and 12-month post-infection. RESULTS: Sixty patients completed the evaluations accounting for 33 and 27 patients in group 1 and 2, respectively. The 1-month TDI score (23.7 ± 5.3) was significantly lower in group 2 compared to group 1 (29.8 ± 8.7; p = 0.017). Proportion of normosmic patients at 1-month post-infection was significantly higher in group 1 compared to group 2 (p = 0.009). TDI scores only significantly increased from 1- to 3-month post-infection in anosmic and hyposmic patients. Focusing on There was a negative association between the 1-month ODQ and the 1-month TDI (rs = - 0.493; p = 0.012). ODQ was a significant predictor of TDI scores at 3- and 12-month post-infection. The 12-month prevalence of parosmia was 60.6% in group 1 and 42.4% in group 2, respectively. There was no significant influence of oral corticosteroid treatment, adherence to an olfactory training and vaccination status on the olfactory outcomes. CONCLUSIONS: Patients of the second wave (Alpha B.1.1.7. variant) reported significant higher proportion of psychophysical test abnormalities at 1-month post-infection than patients infected during the first wave (D614G virus).

Macrophage Profiling in Head and Neck Cancer to Improve Patient Prognosis and Assessment of Cancer Cell-Macrophage Interactions Using Three-Dimensional Coculture Models.

Tumor-associated macrophages are key components of the tumor microenvironment and play important roles in the progression of head and neck cancer, leading to the development of effective strategies targeting immune cells in tumors. Our study demonstrated the prognostic potential of a new scoring system (Macroscore) based on the combination of the ratio and the sum of the high and low densities of M1 (CD80+) and M2 (CD163+) macrophages in a series of head and neck cancer patients, including a training population (n = 54) and a validation population (n = 19). Interestingly, the Macroscore outperformed TNM criteria and p16 status, showing a significant association with poor patient prognosis, and demonstrated significant predictive value for overall survival. Additionally, 3D coculture spheroids were established to analyze the crosstalk between cancer cells and monocytes/macrophages. Our data revealed that cancer cells can induce monocyte differentiation into protumoral M2 macrophages, creating an immunosuppressive microenvironment. This coculture also induced the production of immunosuppressive cytokines, such as IL10 and IL8, known to promote M2 polarization. Finally, we validated the ability of the macrophage subpopulations to induce apoptosis (M1) or support proliferation (M2) of cancer cells. Overall, our research highlights the potential of the Macroscore as a valuable prognostic biomarker to enhance the clinical management of patients and underscores the relevance of a spheroid model in gaining a better understanding of the mechanisms underlying cancer cell-macrophage interactions.

Association between laryngopharyngeal reflux, gastroesophageal reflux and recalcitrant chronic rhinosinusitis: A systematic review.

OBJECTIVE: To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). DATA SOURCES: PubMed, Cochrane Library and Scopus. REVIEW METHODS: Three investigators searched the specified databases for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. The authors performed a bias analysis of papers and provided recommendations for future studies. RESULTS: A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The number of hypo- and nasopharyngeal acid reflux events was significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one study did not report intergroup differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was significant heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the ability to draw clear conclusions. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls. CONCLUSION: Laryngopharyngeal reflux and GERD may be contributing factors of CRS therapeutic resistance, but future studies are needed to confirm the association considering nonacid reflux events.

Bufalin for an innovative therapeutic approach against cancer.

Bufalin is an endogenous cardiotonic steroid, first discovered in toad venom but also found in the plasma of healthy humans, with anti-tumour activities in different cancer types. The current review is focused on its mechanisms of action and highlights its very large spectrum of effects both in vitro and in vivo. All leads to the conclusion that bufalin mediates its effects by affecting all the hallmarks of cancer and seems restricted to cancer cells avoiding side effects. Bufalin decreases cancer cell proliferation by acting on the cell cycle and inducing different mechanisms of cell death including apoptosis, necroptosis, autophagy and senescence. Bufalin also moderates metastasis formation by blocking migration and invasion as well as angiogenesis and by inducing a phenotype switch towards differentiation and decreasing cancer cell stemness. Regarding its various mechanisms of action in cancer cells, bufalin blocks overactivated signalling pathways and modifies cell metabolism. Moreover, bufalin gained lately a huge interest in the field of drug resistance by both reversing various drug resistance mechanisms and affecting the immune microenvironment. Together, these data support bufalin as a quite promising new anti-cancer drug candidate.

Laryngopharyngeal reflux may be acute, recurrent or chronic disease: preliminary observations.

OBJECTIVE: To investigate the mid-to-long-term symptom evolution and treatment findings of laryngopharyngeal reflux (LPR) patients. METHODS: Patients with LPR and treated between September 2016 and December 2017 were prospectively followed. The diagnosis consisted of > 1 pharyngeal event at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring. The treatment consisted of 3- to 9-months diet, stress management and medication according to the type of LPR. Reflux symptom score was used to assess the therapeutic response. Patients were surveyed yearly to know the reflux evolution, the potential recurrence(s) of symptoms, and the approaches used to control the disease. RESULTS: A total of 77 patients completed the evaluations (45 females). The initial treatment duration was 3, 6, or 9 months in 25 (32.5%), 23 (29.9%), and 6 (7.7%) cases before weaning, respectively. Twenty-three patients (29.9%) reported chronic course of the disease. According to the reduction of reflux symptom score, symptoms did not change in 11 (14.3%) patients, while the rest of the patients reported symptom reduction or relief (responder rate of 85.7%). Over time, LPR symptoms never relapsed in 31% of cases, while 38% of patients reported one or several recurrences a year. The recurrence episodes of patients were all adequately treated with medication or diet and did not require long-term medication. CONCLUSION: Chronic course of the disease was observed in 31% of patients who required long-term medication. Preliminary observations reported that LPR may be classified as acute, recurrent, or chronic disease. The medication weaning is possible in most patients, leading to reduction of cost burden related to LPR treatment.

Effectiveness and safety of PRP on persistent olfactory dysfunction related to COVID-19.

INTRODUCTION: Olfactory dysfunction (OD) is a well know symptom of coronavirus disease 2019 (COVID-19), accounting for 48 to 85% of patients. In 1 to 10% of cases, patients develop a chronic olfactory dysfunction (COD), lasting more than 6 months. Recently, platelet-rich plasma (PRP) was used in patients with non-COVID-19 COD and authors reported encouraging results. METHODS: In the present study, we investigated the usefulness and safety of PRP injection in 56 patients with COVID-19 COD by the Sniffing Stick test (TDI score) and a linker-scale from 0 (none) to 3 (strong) and we compare the result to a control group. RESULTS: At 1 month post-PRP injection, the mean TDI scores significantly improved by 6.7 points in the PRP group (p < 0,001), the mean self-assessment of improvement in smell function was 1.8 (mild-to-moderate) in the PRP group, which was significantly higher than the score (0.3) in the control group (p < 0,001). CONCLUSION: Our results showed that PRP in the olfactory cleft can increase the olfactory threshold 1 month after the injection. Moreover, our results suggest that timing of treatment may be an important factor and that PRP is a safe treatment, because no adverse effects were reported throughout the study. TRIAL REGISTRATION NUMBER: NCT05226546.

Acoustic measurements are useful therapeutic indicators of patients with dysphonia-related to reflux.

OBJECTIVES: The objective is to study the usefulness of acoustic measurements as therapeutic outcomes for patients with dysphonia related to laryngopharyngeal reflux (LPR). METHODS: From September 2019 to April 2021, 120 patients with LPR at the hypopharyngeal-esophageal multichannel intraluminal impedance pH-monitoring (HEMII-pH) were prospectively recruited from three University Hospitals. They were divided in two groups regarding the presence of dysphonia. The treatment consisted of a combination of diet, proton-pump inhibitors, magaldrate and alginate for 3-6 months. The following clinical and acoustic evaluations were studied regarding groups at baseline, 3- and 6-month posttreatment: reflux symptom score (RSS), reflux sign assessment (RSA), percent jitter, percent shimmer and noise-to-harmonic ratio (NHR). RESULTS: A total of 109 patients completed the evaluations, accounting for 49 dysphonic and 60 non-dysphonic individuals. HEMII-pH, gastrointestinal endoscopy, baseline clinical and acoustic features were comparable between groups. RSS and RSA significantly improved from pre- to 3-month posttreatment in both groups. Jitter, Shimmer and NHR significantly improved from pre- to 3-month posttreatment in dysphonic patients, without additional 3- to 6-month posttreatment changes. Acoustic parameters did not change throughout treatment in patients without dysphonia. CONCLUSION: Acoustic measurements may be an interesting indicator of treatment in LPR patients who reported dysphonia. In this group of individuals, the evolution of acoustic parameters was consistent with the evolution of symptoms and findings.

Neutrophil-to-lymphocyte ratio as a prognostic marker for head and neck cancer with lung metastasis: a retrospective study.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is the most widely biomarker used to assess the inflammatory system in various solid cancers. An elevated NLR has been reported to be associated with worse outcomes in head and neck squamous cell cancers (HNSCC). However, questions remain about the prognostic value of these findings in HNSCC patients with lung metastasis. This study aims to quantify the prognostic impact of NLR on HNSCC patients with lung metastasis. METHODS: A retrospective chart review of 169 HNSCC patients was performed at the Otorhinolaryngology and the Stomatology and Maxillofacial Surgery Department (Saint-Pierre Hospital), between 2000 and 2017. All patients were divided into two subgroups. Patients who developed lung involvement were assigned to the lung-metastasis-group (LM-group) in contrast to no-lung-metastasis-group patients (NLM-group). The prognostic significance of NLR was evaluated using multivariable analysis adjusting for overall-survival (OS) and lung-metastasis-free-survival (LMFS). RESULTS: 95 patients were enrolled in the NLM-group while 74 were in the LM-group. Multivariable analysis highlights that patients with a higher NLR value had shortened OS in the NLM subgroup (HR 1.3; p = 0.024). However, this association was not found in the LM subgroup. When considering both subgroups, an elevated NLR was reported as a prognostic factor of poor LMFS (HR 1.65; p = 0.047). CONCLUSION: Our data revealed that pretreatment NLR is an independent prognostic factor of mortality and lung metastasis development. However, the prognostic value of NLR is not confirmed in patients who suffered from lung metastasis. Physicians should integrate these findings in their treatment algorithm approach.

Proof-of-concept of a new FFP2 mask adapted to Otolaryngological practice in pandemic: a prospective study.

OBJECTIVE: The objective of this study was to appreciate the tolerance and convenience of a new FFP2 mask allowed the realization of nasal examination in period of pandemic. METHODS: Fifty-one patients were prospectively recruited from two European hospitals to test the FFP2 mask prototype. The following outcomes were evaluated in patients after the clinical examination: fear about coronavirus disease 2019 (COVID-19) infection; easiness of mask placement; tolerability; reassurance; and overall satisfaction about the use of this kind of mask in a pandemic context. Seven otolaryngologists evaluated the mask acceptance and usefulness in patients through a standardized physician-reported outcome questionnaire. RESULTS: Fifty patients completed the evaluation. There were 25 males and 25 females. The mean age of patients was 41 years. Ninety percent of patients considered that the use of the mask reduced the risk to be infected during the examination. Seventy percent of patients reported high or very high satisfaction and should recommend mask to other patients in pandemic period. The realization of nasal examination was easier with optic compared with flexible trans-nasal examination (p = 0.001), which significantly impacted the satisfaction level of physician (p = 0.001). The physician difficulty to perform the examination significantly impacted the satisfactory of patient (p = 0.033). CONCLUSION: The new bioserenity FFP2 mask allows the realization of the trans-nasal endoscopic examination during a pandemic. The use of this mask requires little training period of physician. The use of this mask prototype is well received by patients who reported better perception of self-protection against the virus.

Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study.

BACKGROUND: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. RESULTS: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7-18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs = 0.182) and not significant (p = 0.12). CONCLUSIONS: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions.

Dealing with Macrophage Plasticity to Address Therapeutic Challenges in Head and Neck Cancers.

The head and neck tumor microenvironment (TME) is highly infiltrated with macrophages. More specifically, tumor-associated macrophages (TAM/M2-like) are one of the most critical components associated with poor overall survival in head and neck cancers (HNC). Two extreme states of macrophage phenotypes are described as conducting pro-inflammatory/anti-tumoral (M1) or anti-inflammatory/pro-tumoral (M2) activities. Moreover, specific metabolic pathways as well as oxidative stress responses are tightly associated with their phenotypes and functions. Hence, due to their plasticity, targeting M2 macrophages to repolarize in the M1 phenotype would be a promising cancer treatment. In this context, we evaluated macrophage infiltration in 60 HNC patients and demonstrated the high infiltration of CD68+ cells that were mainly related to CD163+ M2 macrophages. We then optimized a polarization protocol from THP1 monocytes, validated by specific gene and protein expression levels. In addition, specific actors of glutamine pathway and oxidative stress were quantified to indicate the use of glutaminolysis by M2 and the production of reactive oxygen species by M1. Finally, we evaluated and confirmed the plasticity of our model using M1 activators to repolarize M2 in M1. Overall, our study provides a complete reversible polarization protocol allowing us to further evaluate various reprogramming effectors targeting glutaminolysis and/or oxidative stress in macrophages.

A structural equation model to examine the clinical features of mild-to-moderate COVID-19: A multicenter Italian study.

The purpose of this study was to evaluate the clinical features of mild-to-moderate coronavirus disease 2019 (COVID-19) in a sample of Italian patients and to investigate the occurrence of smell and taste disorders. Infected individuals with suspected (clinical diagnosis) or laboratory-confirmed COVID-19 infection were recruited. Patients completed a survey-based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms, and smell and taste disorders. A total of 294 patients with mild-to-moderate COVID-19 completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough, and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above-mentioned disorders was found (rs: 0.412; P < .001). Smell disorders occurred before the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory-confirmed diagnosis (polymerase chain reaction) group. The structural equation model confirmed significant standardized paths (P < .05) between general symptoms, comorbidities, and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations. The prevalence of smell and taste disorders in mild-to-moderate Italian COVID-19 patients is significant both in suspected and laboratory-confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea.

Predictive factors of smell recovery in a clinical series of 288 coronavirus disease 2019 patients with olfactory dysfunction.

BACKGROUND AND PURPOSE: The aim was to evaluate potential predictive factors of smell recovery in a clinical series of 288 patients presenting olfactory dysfunction (OD) related to coronavirus disease 2019 (COVID-19). Potential correlations were sought between epidemiological, clinical and immunological characteristics of patients and the persistence of OD at 60 days. METHODS: COVID-19 positive patients presenting OD were prospectively recruited from three European hospitals. Baseline clinical and olfactory evaluations were performed within the first 2 weeks after OD onset and repeated at 30 and 60 days. In a subgroup of patients, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured in serum, saliva and nasal secretions at 60 days. RESULTS: A total of 288 COVID-19 patients with OD were included in the study. Two weeks after the onset of the loss of smell, 52.4% of patients had OD on psychophysical tests, including 113 cases (39.2%) of anosmia and 38 cases (13.2%) of hyposmia. At 60-day follow-up, 25.4% of the patients presented persistent OD. There was no significant correlation between sex, age, viral load on nasopharyngeal swab or COVID-19 severity and poor olfactory outcome. In a subgroup of 63 patients, it was demonstrated that patients with poor olfactory outcomes at 60 days had lower levels of salivary and nasal immunoglobulin G (IgG) and IgG1, but similar levels of antibodies in the serum. CONCLUSIONS: No clinical markers predicted the evolution of OD at 60 days. Patients with poor olfactory outcome at 60 days had lower saliva and nasal antibodies, suggesting a role for local immune responses in the persistence of COVID-19 related OD.