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1. Use of platelet‐rich plasma for COVID‐19–related olfactory loss: a randomized controlled trial

Author

Yan, Carol H, Jang, Sophie S, Lin, Hung‐Fu C, Ma, Yifei, Khanwalkar, Ashoke R, Thai, Anthony, and Patel, Zara M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Behavioral and Social Science, Neurosciences, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Humans, Anosmia, Olfaction Disorders, COVID-19, Smell, Platelet-Rich Plasma, anosmia, long COVID, olfaction, persistent olfactory dysfunction, platelet-rich plasma, post COVID syndrome, PRP, smell loss, therapeutics, Immunology, Clinical sciences
Abstract

IntroductionThe current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss.MethodsThis multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale.ResultsA total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported.ConclusionOlfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.

Published
2023

2. Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers

Author

Nakayama, Tsuguhisa, Lee, Ivan T, Jiang, Sizun, Matter, Matthias S, Yan, Carol H, Overdevest, Jonathan B, Wu, Chien-Ting, Goltsev, Yury, Shih, Liang-Chun, Liao, Chun-Kang, Zhu, Bokai, Bai, Yunhao, Lidsky, Peter, Xiao, Yinghong, Zarabanda, David, Yang, Angela, Easwaran, Meena, Schürch, Christian M, Chu, Pauline, Chen, Han, Stalder, Anna K, McIlwain, David R, Borchard, Nicole A, Gall, Phillip A, Dholakia, Sachi S, Le, Wei, Xu, Le, Tai, Chih-Jaan, Yeh, Te-Huei, Erickson-Direnzo, Elizabeth, Duran, Jason M, Mertz, Kirsten D, Hwang, Peter H, Haslbauer, Jasmin D, Jackson, Peter K, Menter, Thomas, Andino, Raul, Canoll, Peter D, DeConde, Adam S, Patel, Zara M, Tzankov, Alexandar, Nolan, Garry P, and Nayak, Jayakar V

Subjects
Dental/Oral and Craniofacial Disease, Tobacco, Prevention, Biodefense, Pneumonia & Influenza, Emerging Infectious Diseases, Infectious Diseases, Pneumonia, Tobacco Smoke and Health, Clinical Research, Vaccine Related, Lung, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Respiratory, Good Health and Well Being, Aged, Aged, 80 and over, Angiotensin-Converting Enzyme 2, COVID-19, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Nasal Cavity, Respiratory Mucosa, SARS-CoV-2, Serine Endopeptidases, Smokers, Trachea, Viral Tropism, ACE2, IFN-β1, TMPRSS2, ciliated epithelial cell, nasal cavity, smoking, trachea, upper airway
Abstract

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.

Published
2021

3. ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs.

Author

Lee, Ivan T, Nakayama, Tsuguhisa, Wu, Chien-Ting, Goltsev, Yury, Jiang, Sizun, Gall, Phillip A, Liao, Chun-Kang, Shih, Liang-Chun, Schürch, Christian M, McIlwain, David R, Chu, Pauline, Borchard, Nicole A, Zarabanda, David, Dholakia, Sachi S, Yang, Angela, Kim, Dayoung, Chen, Han, Kanie, Tomoharu, Lin, Chia-Der, Tsai, Ming-Hsui, Phillips, Katie M, Kim, Raymond, Overdevest, Jonathan B, Tyler, Matthew A, Yan, Carol H, Lin, Chih-Feng, Lin, Yi-Tsen, Bau, Da-Tian, Tsay, Gregory J, Patel, Zara M, Tsou, Yung-An, Tzankov, Alexandar, Matter, Matthias S, Tai, Chih-Jaan, Yeh, Te-Huei, Hwang, Peter H, Nolan, Garry P, Nayak, Jayakar V, and Jackson, Peter K

Subjects
Goblet Cells, Respiratory System, Lung, Cilia, Endothelial Cells, Humans, Pneumonia, Viral, Coronavirus Infections, Sinusitis, Peptidyl-Dipeptidase A, Angiotensin-Converting Enzyme Inhibitors, Smoking, Age Factors, Sex Factors, Gene Expression, Angiotensin Receptor Antagonists, Pandemics, COVID-19, Angiotensin-Converting Enzyme 2, Pneumonia, Viral
Abstract

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

Published
2020

4. More than smell – COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Author

Parma, Valentina, Ohla, Kathrin, Veldhuizen, Maria G, Niv, Masha Y, Kelly, Christine E, Bakke, Alyssa J, Cooper, Keiland W, Bouysset, Cédric, Pirastu, Nicola, Dibattista, Michele, Kaur, Rishemjit, Liuzza, Marco Tullio, Pepino, Marta Y, Schöpf, Veronika, Pereda-Loth, Veronica, Olsson, Shannon B, Gerkin, Richard C, Domínguez, Paloma Rohlfs, Albayay, Javier, Farruggia, Michael C, Bhutani, Surabhi, Fjaeldstad, Alexander W, Kumar, Ritesh, Menini, Anna, Bensafi, Moustafa, Sandell, Mari, Konstantinidis, Iordanis, Di Pizio, Antonella, Genovese, Federica, Öztürk, Lina, Thomas-Danguin, Thierry, Frasnelli, Johannes, Boesveldt, Sanne, Saatci, Özlem, Saraiva, Luis R, Lin, Cailu, Golebiowski, Jérôme, Hwang, Liang-Dar, Ozdener, Mehmet Hakan, Guàrdia, Maria Dolors, Laudamiel, Christophe, Ritchie, Marina, Havlícek, Jan, Pierron, Denis, Roura, Eugeni, Navarro, Marta, Nolden, Alissa A, Lim, Juyun, Whitcroft, KL, Colquitt, Lauren R, Ferdenzi, Camille, Brindha, Evelyn V, Altundag, Aytug, Macchi, Alberto, Nunez-Parra, Alexia, Patel, Zara M, Fiorucci, Sébastien, Philpott, Carl M, Smith, Barry C, Lundström, Johan N, Mucignat, Carla, Parker, Jane K, van den Brink, Mirjam, Schmuker, Michael, Fischmeister, Florian Ph S, Heinbockel, Thomas, Shields, Vonnie DC, Faraji, Farhoud, Santamaría, Enrique, Fredborg, William EA, Morini, Gabriella, Olofsson, Jonas K, Jalessi, Maryam, Karni, Noam, D’Errico, Anna, Alizadeh, Rafieh, Pellegrino, Robert, Meyer, Pablo, Huart, Caroline, Chen, Ben, Soler, Graciela M, Alwashahi, Mohammed K, Welge-Lüssen, Antje, Freiherr, Jessica, de Groot, Jasper HB, Klein, Hadar, Okamoto, Masako, Singh, Preet Bano, Hsieh, Julien W, Reed, Danielle R, Hummel, Thomas, Munger, Steven D, Hayes, John E, Abdulrahman, Olagunju, Dalton, Pamela, Yan, Carol H, Voznessenskaya, Vera V, Chen, Jingguo, Sell, Elizabeth A, and Walsh-Messinger, Julie

Subjects
Neurosciences, Dental/Oral and Craniofacial Disease, Clinical Research, Adult, Aged, Betacoronavirus, COVID-19, Coronavirus Infections, Female, Humans, Male, Middle Aged, Olfaction Disorders, Pandemics, Pneumonia, Viral, SARS-CoV-2, Self Report, Smell, Somatosensory Disorders, Surveys and Questionnaires, Taste, Taste Disorders, Young Adult, head and neck surgery, olfaction, somatosensation, GCCR Group Author, Biological Sciences, Neurology & Neurosurgery
Abstract

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Published
2020

5. Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial

Author

Yan, Carol H, Rathor, Aakanksha, Krook, Kaelyn, Ma, Yifei, Rotella, Melissa R, Dodd, Robert L, Hwang, Peter H, Nayak, Jayakar V, Oyesiku, Nelson M, DelGaudio, John M, Levy, Joshua M, Wise, Justin, Wise, Sarah K, and Patel, Zara M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Prevention, Cancer, Clinical Research, Complementary and Integrative Health, Nutrition, Neurosciences, Rare Diseases, Adult, Dietary Supplements, Fatty Acids, Omega-3, Female, Humans, Male, Middle Aged, Neuroendoscopy, Olfaction Disorders, Pituitary Neoplasms, Postoperative Cognitive Complications, Prospective Studies, Skull Base Neoplasms, Treatment Outcome, Olfactory loss, Skull base, Pituitary, Endoscopic, Smell, Therapeutics, Sella, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundEndoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration.ObjectiveTo evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection.MethodsIn this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively.ResultsEighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P = .02 and P = .01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P = .03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P = .04).ConclusionOmega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

Published
2020

6. The use of platelet‐rich plasma in treatment of olfactory dysfunction: A pilot study

Author

Yan, Carol H, Mundy, David C, and Patel, Zara M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, hyposmia, olfaction, platelet-rich plasma, postviral, smell loss, platelet‐rich plasma
Abstract

BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI  16 but  30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2b

Published
2020

9. The utility of a “second look” debridement following endonasal skull base surgery in the pediatric population

Author

CHANG, MICHAEL T, additional, Huang, Alice E., additional, Quon, Jennifer L., additional, Fernandez Miranda, Juan Carlos, additional, Wen, Christopher Z., additional, Eide, Jacob G, additional, Kshirsagar, Rijul Sudhir, additional, Qian, Zhen Jason, additional, Nayak, Jayakar, additional, Hwang, Peter, additional, Adappa, Nithin, additional, and Patel, Zara M, additional

Published
2023
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10. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic

Author

Bonilla, Hector, primary, Quach, Tom C., additional, Tiwari, Anushri, additional, Bonilla, Andres E., additional, Miglis, Mitchell, additional, Yang, Phillip C., additional, Eggert, Lauren E., additional, Sharifi, Husham, additional, Horomanski, Audra, additional, Subramanian, Aruna, additional, Smirnoff, Liza, additional, Simpson, Norah, additional, Halawi, Houssan, additional, Sum-ping, Oliver, additional, Kalinowski, Agnieszka, additional, Patel, Zara M., additional, Shafer, Robert William, additional, and Geng, Linda C., additional

Published
2023
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13. International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System

Author

Lechner, Matt, additional, Takahashi, Yoko, additional, Turri-Zanoni, Mario, additional, Ferrari, Marco, additional, Liu, Jacklyn, additional, Counsell, Nicholas, additional, Mattavelli, Davide, additional, Rampinelli, Vittorio, additional, Vermi, William, additional, Lombardi, Davide, additional, Saade, Rami, additional, Park, Ki Wan, additional, Schartinger, Volker H., additional, Franchi, Alessandro, additional, Facco, Carla, additional, Sessa, Fausto, additional, Battocchio, Simonetta, additional, Fenton, Tim R., additional, Vaz, Francis M., additional, O'Flynn, Paul, additional, Howard, David, additional, Stimpson, Paul, additional, Wang, Simon, additional, Hannan, S. Alam, additional, Unadkat, Samit, additional, Hughes, Jonathan, additional, Dwivedi, Raghav, additional, Forde, Cillian T., additional, Randhawa, Premjit, additional, Gane, Simon, additional, Joseph, Jonathan, additional, Andrews, Peter J., additional, Dave, Manas, additional, Fleming, Jason C., additional, Thomson, David, additional, Zhu, Tianyu, additional, Teschendorff, Andrew, additional, Royle, Gary, additional, Steele, Christopher, additional, Jimenez, Joaquin E., additional, Laco, Jan, additional, Wang, Eric W., additional, Snyderman, Carl, additional, Lacy, Peter D., additional, Woods, Robbie, additional, O'Neill, James P., additional, Saraswathula, Anirudh, additional, Kaur, Raman Preet, additional, Zhao, Tianna, additional, Ramanathan, Murugappan, additional, Gallia, Gary L., additional, London, Nyall R., additional, Le, Quynh-Thu, additional, West, Robert B., additional, Patel, Zara M., additional, Nayak, Jayakar V., additional, Hwang, Peter H., additional, Hermsen, Mario, additional, Llorente, Jose, additional, Facchetti, Fabio, additional, Nicolai, Piero, additional, Bossi, Paolo, additional, Castelnuovo, Paolo, additional, Jay, Amrita, additional, Carnell, Dawn, additional, Forster, Martin D., additional, Bell, Diana M., additional, Lund, Valerie J., additional, and Hanna, Ehab Y., additional

Published
2022
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14. Multicenter Analysis of Clinical Outcomes of Sinonasal Mucosal Melanoma

Author

Lechner, Matt, additional, Takahashi, Yoko, additional, Turri-Zanoni, Mario, additional, Ferrari, Marco, additional, Liu, Jacklyn, additional, Counsell, Nicholas, additional, Mattavelli, Davide, additional, Rampinelli, Vittorio, additional, Lombardi, Davide, additional, Saade, Rami, additional, Park, Ki Wan, additional, Schartinger, Volker H., additional, Franchi, Alessandro, additional, Maragliano, Roberta, additional, Battocchio, Simonetta, additional, Emanuel, Oscar, additional, Fenton, Tim, additional, Vaz, Francis M., additional, O'Flynn, Paul, additional, Howard, David, additional, Stimpson, Paul, additional, Wang, Simon, additional, Hannan, S. Alam, additional, Unadkat, Samit, additional, Hughes, Jonathan, additional, Dwivedi, Raghav, additional, Forde, Cillian T., additional, Randhawa, Premjit, additional, Gane, Simon, additional, Joseph, Jonathan, additional, Andrews, Peter J., additional, Zhu, Tianyu, additional, Teschendorff, Andrew, additional, Royle, Gary, additional, Bewicke-Copley, Helen, additional, Steele, Christopher, additional, Williams, Luke, additional, Jimenez-Garcia, Joaquin E., additional, Wang, Eric W., additional, Snyderman, Carl, additional, Lacy, Peter, additional, Woods, Robbie, additional, O'Neill, James P., additional, Le, Quynh-Thu, additional, West, Robert B., additional, Patel, Zara M., additional, Nayak, Jayakar, additional, Hwang, Peter H., additional, Hermsen, Mario, additional, Llorente, Jose, additional, Facchetti, Fabio, additional, Nicolai, Piero, additional, Bossi, Paolo, additional, Castelnuovo, Paolo, additional, Jay, Amrita, additional, Carnell, Dawn, additional, Forster, Martin D., additional, Bell, Diana M., additional, Lund, Valerie J., additional, and Hanna, Ehab Y., additional

Published
2022
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18. Mere end lugtesans - COVID-19 er associeret med svær påvirkning af lugtesansen, smagssansen og mundfølelsen

Author

Parma, Valentina, Ohla, Kathrin, Veldhuizen, Maria G, Niv, Masha Y, Kelly, Christine E, Bakke, Alyssa J, Cooper, Keiland W, Bouysset, Cédric, Pirastu, Nicola, Dibattista, Michele, Kaur, Rishemjit, Liuzza, Marco Tullio, Pepino, Marta Y, Schöpf, Veronika, Pereda-Loth, Veronica, Olsson, Shannon B, Gerkin, Richard C, Rohlfs Domínguez, Paloma, Albayay, Javier, Farruggia, Michael C, Bhutani, Surabhi, Fjaeldstad, Alexander W, Kumar, Ritesh, Menini, Anna, Bensafi, Moustafa, Sandell, Mari, Konstantinidis, Iordanis, Di Pizio, Antonella, Genovese, Federica, Öztürk, Lina, Thomas-Danguin, Thierry, Frasnelli, Johannes, Boesveldt, Sanne, Saatci, Özlem, Saraiva, Luis R, Lin, Cailu, Golebiowski, Jérôme, Hwang, Liang-Dar, Ozdener, Mehmet Hakan, Guàrdia, Maria Dolors, Laudamiel, Christophe, Ritchie, Marina, Havlícek, Jan, Pierron, Denis, Roura, Eugeni, Navarro, Marta, Nolden, Alissa A, Lim, Juyun, Whitcroft, Katherine L, Colquitt, Lauren R, Ferdenzi, Camille, Brindha, Evelyn V, Altundag, Aytug, Macchi, Alberto, Nunez-Parra, Alexia, Patel, Zara M, Fiorucci, Sébastien, Philpott, Carl M, Smith, Barry C, Lundström, Johan N, Mucignat, Carla, Parker, Jane K, van den Brink, Mirjam, Schmuker, Michael, Fischmeister, Florian Ph S, Heinbockel, Thomas, Shields, Vonnie D C, Faraji, Farhoud, Santamaría, Enrique, Fredborg, William E A, Morini, Gabriella, Olofsson, Jonas K, Jalessi, Maryam, Karni, Noam, D’Errico, Anna, Alizadeh, Rafieh, Pellegrino, Robert, Meyer, Pablo, Huart, Caroline, Chen, Ben, Soler, Graciela M, Alwashahi, Mohammed K, Welge-Lüssen, Antje, Freiherr, Jessica, de Groot, Jasper H B, Klein, Hadar, Okamoto, Masako, Singh, Preet Bano, Hsieh, Julien W, Abdulrahman, Olagunju, Dalton, Pamela, Yan, Carol H, Voznessenskaya, Vera V, Chen, Jingguo, Sell, Elizabeth A, Walsh-Messinger, Julie, Archer, Nicholas S, Koyama, Sachiko, Deary, Vincent, Roberts, S Craig, Yanık, Hüseyin, Albayrak, Samet, Nováková, Lenka Martinec, Croijmans, Ilja, Mazal, Patricia Portillo, Moein, Shima T, Margulis, Eitan, Mignot, Coralie, Mariño, Sajidxa, Georgiev, Dejan, Kaushik, Pavan K, Malnic, Bettina, Wang, Hong, Seyed-Allaei, Shima, Yoluk, Nur, Razzaghi-Asl, Sara, Justice, Jeb M, Restrepo, Diego, Reed, Danielle R, Hummel, Thomas, Munger, Steven D, Hayes, John E, Indústries Alimentàries, Qualitat i Tecnologia Alimentària, Tecnologia Alimentària, Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, Mersin University, The Hebrew University of Jerusalem (HUJ), AbScent, Pennsylvania State University (Penn State), Penn State System, University of California [Irvine] (UC Irvine), University of California (UC), Université Côte d'Azur (UCA), University of Edinburgh, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Central Scientific Instruments Organisation (CSIR), Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Medizinische Universität Wien = Medical University of Vienna, Groupement scientifique de Biologie et de Medecine Spatiale (GSBMS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES), Tata Institute for Fundamental Research (TIFR), Arizona State University [Tempe] (ASU), Universidad de Extremadura - University of Extremadura (UEX), Università degli Studi di Padova = University of Padua (Unipd), Yale School of Medicine [New Haven, Connecticut] (YSM), San Diego State University (SDSU), Aarhus University [Aarhus], University of Hertfordshire [Hatfield] (UH), Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies (SISSA / ISAS), Neurosciences Sensorielles Comportement Cognition, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Turku, Aristotle University of Thessaloniki, Leibniz-Institute for Food Systems Biology at the Technical University of Munich, Monell Chemical Senses Center, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Montréal (UdeM), Wageningen University and Research Centre (WUR), Medical Science University, Sidra Medicine [Doha, Qatar], Institut de Chimie de Nice (ICN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), University of Southern Queensland (USQ), Institut de Recerca i Tecnologia Agroalimentàries = Institute of Agrifood Research and Technology (IRTA), DreamAir Llc, Charles University [Prague] (CU), Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Massachusetts System (UMASS), Oregon State University (OSU), Ear Institute, UCL, Lyon Neuroscience Research center, Karunya University, Biruni University, Assi Sette Llaghi Varese, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, University of East Anglia [Norwich] (UEA), California Department of Food and Agriculture (CDFA), Unité mixte de recherche interactions plantes-microorganismes, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Maastricht University [Maastricht], Institute for Biology - Neurobiology, Freie Universität Berlin, Karl-Franzens-Universität Graz, Howard University College of Medicine, Towson University, University of California [San Diego] (UC San Diego), Proteomics, Center for Applied Medical Research (CIMA), Stockholm University, University of Gastronomic Sciences, Iran University of Medical Sciences, Goethe Universität Frankfurt, University of Tennessee, IBM T.J. Watson Research Center, Université libre de Bruxelles (ULB), Guangzhou Medical University, Buenos Aires University and GEOG (Grupo de Estudio de Olfato y Gusto), Sultan Qaboos University (SQU), Federal University of Technology of Akure (FUTA), A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences [Moscow] (RAS), Hospital of Xi'an Jiaotong University, University of Pennsylvania, University of Dayton, CSIRO Agriculture and Food (CSIRO), Indiana University [Bloomington], Indiana University System, University of Northumbria at Newcastle [United Kingdom], University of Stirling, Middle East Technical University [Ankara] (METU), Utrecht University [Utrecht], Instituto Universitario del Hospital Italiano [Buenos Aires, Argentina], Institute for Research in Fundamental Sciences [Tehran] (IPM), Hebrew University of Jerusalem, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Terrazas del Club Hipico, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Tata Institute of Fundamental Research [Bangalore], Universidade de São Paulo = University of São Paulo (USP), University of Florida [Gainesville] (UF), University of Colorado Anschutz [Aurora], Center for Smell and Taste, Department of Food Science, Pennsylvania State University., Julien, Sabine, Tıp Fakültesi, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service d'oto-rhino-laryngologie, Department of Food and Nutrition, Senses and Food, Research Center Jülich, University of California [Irvine] (UCI), University of California, Università degli studi di Bari Aldo Moro (UNIBA), Università degli Studi 'Magna Graecia' di Catanzaro [Catanzaro, Italie] (UMG), University of Extremadura, University of Padova, Yale University School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, University of Helsinki, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institute of Agrifood Research and Technology (IRTA), Universita degli Studi di Padova, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Karl-Franzens-Universität [Graz, Autriche], University of California San Diego Health, University of Brussels, University of Pennsylvania [Philadelphia], Tata Institute of Fundamental Research, University of São Paulo (USP), UCL - SSS/IONS - Institute of NeuroScience, FSE Campus Venlo, and RS: FSE UCV

Subjects
Male, Taste, Physiology, Smagstab, Audiology, AcademicSubjects/SCI01180, Settore BIO/09 - Fisiologia, Behavioral Neuroscience, chemistry.chemical_compound, Olfaction Disorders, Taste Disorders, 0302 clinical medicine, RATINGS, Hyposmia, Surveys and Questionnaires, CHEMOSENSITIVITY, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Viral, PALADAR, 030223 otorhinolaryngology, Sensory Science and Eating Behaviour, media_common, TASTE, US NATIONAL-HEALTH, [SDV.IDA] Life Sciences [q-bio]/Food engineering, Middle Aged, Biological Sciences, 16. Peace & justice, Sensory Systems, 3. Good health, Smell, GCCR Group Author, ddc:540, Smell loss, Female, Original Article, medicine.symptom, Corrigendum, Coronavirus Infections, olfaction, Adult, somatosensation, medicine.medical_specialty, 663/664, Coronavirus disease 2019 (COVID-19), OLFACTORY DISORDERS, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), media_common.quotation_subject, Pneumonia, Viral, head and neck surgery, Aged, Betacoronavirus, COVID-19, Humans, Pandemics, SARS-CoV-2, Self Report, Somatosensory Disorders, Young Adult, Anosmia, Sensory system, Olfaction, 03 medical and health sciences, Chemesthesis, Physiology (medical), Perception, medicine, Neurology & Neurosurgery, Behaviour Change and Well-being, business.industry, R-PACKAGE, 3112 Neurosciences, Pneumonia, Parosmia, COMPONENT, Smagssans, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Sensoriek en eetgedrag, chemistry, Lugtetab, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Lugtesans
Abstract

Correction: Chemical Senses, Volume 46, 2021, bjab050, https://doi.org/10.1093/chemse/bjab050 Published: 08 December 2021 Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change +/- 100) revealed a mean reduction of smell (-79.7 +/- 28.7, mean +/- standard deviation), taste (-69.0 +/- 32.6), and chemesthetic (-37.3 +/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis.The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Published
2020

20. COVID‐19 and the Otolaryngologist: Preliminary Evidence‐Based Review

Author

Vukkadala, Neelaysh, Qian, Z. Jason, Holsinger, F. Christopher, Patel, Zara M., and Rosenthal, Eben

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.disease, Evidence based review, Otorhinolaryngology, Health care, Pandemic, medicine, Medical emergency, business, Close contact
Abstract

The SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19), has rapidly swept across the world since its identification in December 2019. Otolaryngologists are at unique risk due to the close contact with mucus membranes of the upper respiratory tract and have been among the most affected healthcare workers in Wuhan, China. We present information on COVID-19 management relevant to otolaryngologists on the frontlines of this pandemic and provide preliminary guidance based on practices implemented in China and other countries and practical strategies deployed at Stanford University. Laryngoscope, 130:2537-2543, 2020.

Published
2020

21. Corrigendum to: More than smell: COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Author

Parma, Valentina, Ohla, Kathrin, Veldhuizen, Maria G., Niv, Masha Y., Kelly, Christine E., Bakke, Alyssa J., Cooper, Keiland W., Bouysset, Cédric, Pirastu, Nicola, Dibattista, Michele, Kaur, Rishemjit, Liuzza, Marco Tullio, Pepino, Marta Y., Schöpf, Veronika, Pereda-Loth, Veronica, Olsson, Shannon B., Gerkin, Richard C., Rohlfs Domínguez, Paloma, Albayay, Javier, Farruggia, Michael C., Bhutani, Surabhi, Fjaeldstad, Alexander W., Kumar, Ritesh, Menini, Anna, Bensafi, Moustafa, Sandell, Mari, Konstantinidis, Iordanis, Di Pizio, Antonella, Genovese, Federica, Öztürk, Lina, Thomas-Danguin, Thierry, Frasnelli, Johannes, Boesveldt, Sanne, Saatci, Özlem, Saraiva, Luis R., Lin, Cailu, Golebiowski, Jérôme, Hwang, Liang Dar, Ozdener, Mehmet Hakan, Guàrdia, Maria Dolors, Laudamiel, Christophe, Ritchie, Marina, Havlícek, Jan, Pierron, Denis, Roura, Eugeni, Navarro, Marta, Nolden, Alissa A., Lim, Juyun, Whitcroft, Katherine L., Colquitt, Lauren R., Ferdenzi, Camille, Brindha, Evelyn V., Altundag, Aytug, Macchi, Alberto, Nunez-Parra, Alexia, Patel, Zara M., Fiorucci, Sébastien, Philpott, Carl M., Smith, Barry C., Lundström, Johan N., Mucignat, Carla, Parker, Jane K., Van Den Brink, Mirjam, Schmuker, Michael, Fischmeister, Florian Ph S., Heinbockel, Thomas, Shields, Vonnie D.C., Faraji, Farhoud, Santamaría, Enrique, Fredborg, William E.A., Morini, Gabriella, Olofsson, Jonas K., Jalessi, Maryam, Karni, Noam, D'Errico, Anna, Alizadeh, Rafieh, Pellegrino, Robert, Meyer, Pablo, Huart, Caroline, Chen, Ben, Soler, Graciela M., Alwashahi, Mohammed K., Welge-Lüssen, Antje, Freiherr, Jessica, De Groot, Jasper H.B., Klein, Hadar, Okamoto, Masako, Singh, Preet Bano, Hsieh, Julien W., Abdulrahman, Olagunju, Dalton, Pamela, Yan, Carol H., Voznessenskaya, Vera V., Chen, Jingguo, Sell, Elizabeth A., Walsh-Messinger, Julie, Archer, Nicholas S., Koyama, Sachiko, Deary, Vincent, Roberts, S.C., Yanlk, Hüseyin, Albayrak, Samet, Nováková, Lenka Martinec, Croijmans, Ilja, Mazal, Patricia Portillo, Moein, Shima T., Margulis, Eitan, Mignot, Coralie, Mariño, Sajidxa, Georgiev, Dejan, Kaushik, Pavan K., Malnic, Bettina, Wang, Hong, Seyed-Allaei, Shima, Yoluk, Nur, Razzaghi-Asl, Sara, Justice, Jeb M., Restrepo, Diego, Reed, Danielle R., Hummel, Thomas, Munger, Steven D., Hayes, John E., UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service d'oto-rhino-laryngologie

Subjects
Behavioral Neuroscience, Sensoriek en eetgedrag, Behaviour Change and Well-being, Physiology, Physiology (medical), ddc:540, Life Science, Sensory Systems, Sensory Science and Eating Behaviour, VLAG
Abstract

This is a correction notice for article bjaa041 (DOI: https:// doi.org/10.1093/chemse/bjaa041), published 20 June 2020. An incorrect version of the caption to Figure 5 was mistakenly included in the published paper. An updated version is given below. Neither the data nor the paper's conclusions were affected by this correction. The authors sincerely apologize for the error. (A) Correlations between the 3 principal components with respect to changes in 3 chemosensory modalities (i.e., taste, smell, and chemesthesis). Shades of gray indicate positive correlation, whereas shades of red indicate negative correlations. White denotes no correlation. (B) Clusters of participants identified by k-means clustering. The scatterplot shows each participant's loading on dimension 1 (degree of smell and taste loss, PC1 on x-Axis) and dimension 2 (degree of chemesthesis loss, PC2 on y-Axis). Based on the centroid of each cluster, participants in cluster 1 (blue, N = 1767; top left) are generally characterized by significant smell, taste and chemesthesis loss. Participants in cluster 2 (orange, N = 1724; bottom center) are generally characterized by ratings that reflect smell/taste loss with preserved chemesthesis. Loadings for participants in cluster 3 (green, N = 548; right side) are generally characterized by reduced smell and taste loss, and preserved chemesthesis.

Published
2021

22. Acute Bacterial Rhinosinusitis

Author

Patel, Zara M. and Hwang, Peter H.

Subjects
Upper respiratory infection, Acute viral rhinosinusitis, Viral rhinosinusitis, Common cold, otorhinolaryngologic diseases, sense organs, Sinusitis, Acute rhinosinusitis, Acute bacterial sinusitis, Article, Acute sinusitis
Abstract

Acute bacterial rhinosinusitis (ABRS) is a highly prevalent disease associated with significant direct and indirect costs. It is paramount that a practitioner can distinguish between acute viral rhinosinusitis and ABRS to avoid unnecessary antibiotic usage. It is also important to understand that establishing a diagnosis of ABRS does not necessitate the prescribing of antibiotics, unless the ABRS patient presents with severe or worsening symptoms or an ABRS complication. Complications include extension of infection to the orbit and central nervous system. Injudicious use of antibiotics imparts societal costs in terms of financial expense as well as contributing to higher levels of bacterial resistance. This chapter reviews the epidemiology, clinical features, diagnosis, and treatment of ABRS.

Published
2018

23. High-Efficiency, Selection-free Gene Repair in Airway Stem Cells from Cystic Fibrosis Patients Rescues CFTR Function in Differentiated Epithelia

Author

Vaidyanathan, Sriram, primary, Salahudeen, Ameen A., additional, Sellers, Zachary M., additional, Bravo, Dawn T., additional, Choi, Shannon S., additional, Batish, Arpit, additional, Le, Wei, additional, Baik, Ron, additional, de la O, Sean, additional, Kaushik, Milan P., additional, Galper, Noah, additional, Lee, Ciaran M., additional, Teran, Christopher A., additional, Yoo, Jessica H., additional, Bao, Gang, additional, Chang, Eugene H., additional, Patel, Zara M., additional, Hwang, Peter H., additional, Wine, Jeffrey J., additional, Milla, Carlos E., additional, Desai, Tushar J., additional, Nayak, Jayakar V., additional, Kuo, Calvin J., additional, and Porteus, Matthew H., additional

Published
2020
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26. Randomized Controlled Trial Demonstrating Cost‐Effective Method of Olfactory Training in Clinical Practice: Essential Oils at Uncontrolled Concentration

Author

Patel, Zara M., Wise, Sarah K., and DelGaudio, John M.

Subjects
smell loss, General Otolaryngology, randomized controlled trial, olfactory loss, olfactory training, Original Research, olfaction
Abstract

Objectives Published data examining the efficacy of olfactory training (OT) has used standardized concentrations of odorants and the Sniffin’ Sticks testing method. Although well‐validated, these methods are costly and time‐intensive for the average otolaryngology practice. The purpose of our study was to evaluate the efficacy of using essential oils at random concentrations and the University of Pennsylvania Smell Test (UPSIT) for training and testing, and compare this with the existing data on OT. Study Design Randomized Clinical TrialMethods: Patients presenting to a tertiary care rhinology center with subjective loss of smell and olfactory loss measured by UPSIT were randomized to OT or control for 6 months. Only patients with loss of smell greater than one‐year duration, and loss associated with post‐infectious and idiopathic etiologies were included. Baseline UPSIT was compared to 6‐month UPSIT. An accepted 10% change or better was used to establish a significant improvement on UPSIT. Results 43 patients were enrolled. Eight patients were lost to follow‐up, with a total of 35 completing the study. Age ranged from 39–71 with an average of 56. Of 19 patients in the OT group, 6 showed significant improvement (32%), while only two out of 16 patients (13%) in the control group improved. Increasing age and duration of loss were significantly correlated to lack of improvement. Conclusion Allowing patients to use random concentrations of essential oils to perform OT is as effective as published data using controlled concentrations of odorants for post‐infectious and idiopathic olfactory loss. Level of Evidence 1b.

Published
2017

28. Rhinology

Author

Hayes, Katherine and Patel, Zara M.

Subjects
Middle Turbinate, Functional Endoscopic Sinus Surgery, Primary Ciliary Dyskinesia, otorhinolaryngologic diseases, Frontal Sinus, Frontal Recess, Article
Abstract

Osteomas are the most common benign sinonasal lesion with the frontal sinus the most common location. On sinus MRI, dried secretions show as hyperintense on T1, hypointense on T2, and polyps show hypointense on T1, hyperintense on T2. Rhinoscleroma is caused by Klebsiella rhinoscleromatis with histopathology showing Mikulicz cells (macrophages containing pathogen) and Russell bodies (plasma cells).

Published
2013

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