Received: 5 January 2021 | Revised: 23 February 2021 | Accepted: 25 February 2021 DOI: 10.1111/all.14815 ORIGINAL ARTICLE Rhinitis, Sinusitis, and Upper Airway Disease Differentiation of COVID-­19 signs and symptoms from allergic rhinitis and common cold: An ARIA-­EAACI-­GA2LEN consensus Jan Hagemann1 | Gabrielle L. Onorato2 | Marek Jutel3 | Cezmi A. Akdis4 | 5 6 7 Ioana Agache | Torsten Zuberbier | Wienczyslawa Czarlewski | 8 2,9 Joaquim Mullol | Anna Bedbrook | Claus Bachert10,11,12,13 | Kazi S. Bennoor14 | Karl-­Christian Bergmann6 | Fulvio Braido15 | Paulo Camargos16 | Luis Caraballo17,18 | Victoria Cardona19 | Thomas Casale20 | Lorenzo Cecchi21 | Tomas Chivato22 | Derek K. Chu23 | Cemal Cingi24 | Jaime Correia-­de-­Sousa25,26,27 | Stefano del 28 29 30 31 Giacco | Dejan Dokic | Mark Dykewicz | Motohiro Ebisawa | 32 33 34 Yehia El-­Gamal✝ | Regina Emuzyte | Jean-­Luc Fauquert | Alessandro Fiocchi35 | Wytske J. Fokkens36,37 | Joao A. Fonseca38,39 | Bilun Gemicioglu40 | René-­ Maximiliano Gomez41 | Maia Gotua42 | Tari Haahtela43 | Eckard Hamelmann44 | 45 46 47 48 Tomohisa Iinuma | Juan Carlos Ivancevich | Ewa Jassem | Omer Kalayci | 49 50 51 52 Przemyslaw Kardas | Musa Khaitov | Piotr Kuna | Violeta Kvedariene | 53 54 55 Desiree E. Larenas-­Linnemann | Brian Lipworth | Michael Makris | Jorge 56 57 58 F. Maspero | Neven Miculinic | Florin Mihaltan | Yousser Mohammad59 | Stephen Montefort60 | Mario Morais-­Almeida61 | Ralph Mösges62 | 63 64 65 Robert Naclerio | Hugo Neffen | Marek Niedoszytko | Robyn E. O’Hehir66,67 | Ken Ohta68 | Yoshitaka Okamoto45 | Kimi Okubo69 | Petr Panzner70 | 71 72 Nikolaos G. Papadopoulos | Giovanni Passalacqua | 73 74,75,76 77 Vincenzo Patella | Ana Pereira | Oliver Pfaar | Davor Plavec78 | Todor A. Popov79 | Emmanuel P. Prokopakis80 | Francesca Puggioni81 | Filip Raciborski82 | Jere Reijula83 | Frederico S. Regateiro84 | Sietze Reitsma85 | Antonino Romano86,87 | Nelson Rosario88 | Menachem Rottem89 | Dermot Ryan90 | 82 91 92 93 Boleslaw Samolinski | Joaquin Sastre | Dirceu Solé | Milan Sova | 94 95 96 Cristiana Stellato | Charlotte Suppli-­Ulrik | Ioanna Tsiligianni | Antonio Valero97 | Arunas Valiulis98,99 | Erkka Valovirta100 | Tuula Vasankari101,102 | Maria Teresa Ventura103 | Dana Wallace104 | De Yun Wang105 | Siân Williams27 | Arzu Yorgancioglu106 | Osman M. Yusuf107 | Mario Zernotti108 | Jean Bousquet2,6,109 | Ludger Klimek1,110 1 Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, Germany 2 MACVIA-­France, Montpellier, France © 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Allergy. 2021;00:1–13.  wileyonlinelibrary.com/journal/all | 1 2 | HAGEMANN et al. 3 Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland 4 Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland 5 Transylvania University Brasov, Brasov, Romania 6 Comprehensive Allergy Center, Department of Dermatology and Allergy, Charité, Universitätsmedizin Berlin, Humboldt-­Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany 7 Medical Consulting Czarlewski, Levallois, France 8 Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic; Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain 9 MASK-­air, Montpellier, France 10 Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium 11 Sun Yat-­sen University, International Airway Research Center, First Affiliated Hospital Guangzou, Guangzou, China 12 Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden 13 Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden 14 Department of Respiratory Medicine, National Institute of Diseases of the Chest and Hospital, Dhaka, Bangladesh 15 Department of Internal Medicine (DiMI) and IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy 16 Department of Pediatrics, Federal University of Minas Gerais, Medical School, Belo Horizonte, Brazil 17 Institute for Immunological Research, University of Cartagena, Campus de Zaragocilla, Edificio Biblioteca Primer piso, Cartagena, Colombia 18 Foundation for the Development of Medical and Biological Sciences (Fundemeb), Cartagena, Colombia 19 Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron & ARADyAL Research Network, Barcelona, Spain 20 Division of Allergy/immunology, University of South Florida, Tampa, FL, USA 21 SOS Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy 22 School of Medicine, University CEU San Pablo, Madrid, Spain 23 Departments of Medicine and Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, Canada 24 ENT Department, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey 25 Life and Health Sciences Research Institute (ICVS, School of Medicine, University of Minho, Braga, Portugal 26 PT Government Associate Laboratory, Braga/Guimarães, Portugal 27 International Primary Care Respiratory Group IPCRG, London, UK 28 Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital ‘Duilio Casula’, University of Cagliari, Cagliari, Italy 29 University Clinic of Pulmology and Allergy, Medical Faculty Skopje, Skopje, Republic of Macedonia 30 Section of Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA 31 Clinical Research Center for Allergy and Rheumatology, NHO Sagamihara National Hospital, Sagamihara, Japan 32 Pediatric Allergy and Immunology Unit, Children's hospital, Ain Shams University, Cairo, Egypt 33 Clinic of Children's Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania 34 CHU Clermont-­Ferrand, Unité d'Allergologie de l'Enfant, Pole pédiatrique, Hopital Estaing, Clermont-­Ferrand, France 35 Division of Allergy, Department of Pediatric Medicine, The Bambino Gesù Children's Research Hospital Holy see, IRCCS, Rome, Italy 36 Department of Otorhinolaryngology, Academic Medical Centers, AMC, Amsterdam, The Netherlands 37 EUFOREA, Brussels, Belgium 38 CINTESIS, Center for Health Technology and Services Research, Faculdade de Medicina, Universidade do Porto, Porto, Portugal 39 Allergy Unit, CUF Porto, Porto, Portugal 40 Department of Pulmonary Diseases, Istanbul University-­Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey 41 Fundacion Ayre-­Instituto Medico ALAS, Salta, Argentina 42 Center of Allergy and Immunology, Georgian Association of Allergology and Clinical Immunology, Tbilisi, Georgia 43 Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland 44 University Hospital Bielefeld, Children's Center Bethel, EvKB, Bielefeld, Germany 45 Department of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan 46 Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina 47 Department of Allergology, Medical University of Gdańsk, Gdansk, Poland 48 Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey 49 Department of Family Medicine, Medical University of Lodz, Lodz, Poland 50 National Research Center, Institute of Immunology, Federal Medicobiological Agency, Laboratory of Molecular Immunology, Moscow, Russian Federation 51 Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland 52 Department of Pathology, Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University and Institute of Clinical Medicine, Clinic of Chest Diseases and Allergology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania HAGEMANN et al. | 3 53 Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico 54 Scottish Centre for Respiratory Research, Cardiovascular & Diabetes Medicine, Medical Research Institute, Ninewells Hospital, University of Dundee, Dundee, UK 55 Allergy Unit ‘D Kalogeromitros’, 2nd Department of Dermatology and Venereology, National & Kapodistrian University of Athens, ‘Attikon’ University Hospital, Athens, Greece 56 Argentine Association of Allergy and Clinical Immunology, Buenos Aires, Argentina 57 Croatian Pulmonary Society, Zagreb, Croatia 58 National Institute of Pneumology M Nasta, Bucharest, Romania 59 National Center for Research in Chronic Respiratory Diseases, Tishreen University School of Medicine, Latakia and Syrian Private University-­Damascus, Damascus, Syria 60 Respiratory Physician Mater Dei Hospital Malta, Medicine University of Malta, Faculty of Medicine and Surgery University of Medicine, La Valette, Malta 61 Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal 62 CRI-­Clinical Research International-­Ltd, Hamburg, Germany 63 Johns Hopkins School of Medicine, Baltimore, MD, USA 64 Center of Allergy, Immunology and Respiratory Diseases, Santa Fe, Argentina 65 Department of Allergology, Medical University of Gdańsk, Gdansk, Poland 66 Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Vic., Australia 67 Department of Immunology, Monash University, Melbourne, Vic., Australia 68 National Hospital Organization, Tokyo National Hospital, Tokyo, Japan 69 Department of Otolaryngology, Nippon Medical School, Tokyo, Japan 70 Department of Immunology and Allergology, Faculty of Medicine and Faculty Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic 71 Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, UK 72 Allergy and Respiratory Diseases, Ospedale Policlino San Martino -­University of Genoa, Genoa, Italy 73 Division of Allergy and Clinical Immunology, Department of Medicine, Agency of Health ASL Salerno, ‘Santa Maria della Speranza’ Hospital, Salerno, Italy 74 Center for Research in Health Technologies and Information Systems-­CINTESIS, University of Porto, Porto, Portugal 75 Allergy Unit, Instituto CUF Porto and Hospital CUF Porto, Porto, Portugal 76 Department of Community Medicine, Health Information and Decision -­MEDCIDsS, Faculty of Medicina, University of Porto, Porto, Portugal 77 Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-­Universität Marburg, Marburg, Germany 78 Children's Hospital Srebrnjak, Zagreb, School of Medicine, University J.J. Strossmayer, Osijek, Croatia 79 University Hospital ‘Sv Ivan Rilski'", Sofia, Bulgaria 80 Department of Otorhinolaryngology, University of Crete School of Medicine, Heraklion, Greece 81 Personalized Medicine Clinic Asthma & Allergy, Humanitas Clinical and Research Center IRCCS, Rozzano, and Department of Biomedical Sciences, Humanitas University Pieve Emanuele, Milan, Italy 82 Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland 83 Department of Pulmonology, Helsinki University Central Hospital, Helsinki, Department of Public Health, University of Helsinki, Helsinki, Finland 84 Allergy and Clinical Immunology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra and Institute of Immunology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal 85 Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, The Netherlands 86 Oasi Research Institute-­IRCCS, Troina, Italy 87 bFondazione Mediterranea GB Morgagni, Catania, Italy 88 Hospital de Clinicas, University of Parana, Curitiba, Brazil 89 Division of Allergy Asthma and Clinical Immunology, Emek Medical Center, Afula, Israel 90 Usher Institute, University of Edinburgh, Edinburgh, UK 91 Fundacion Jimenez Diaz, CIBERES, Faculty of Medicine, Autonoma University of Madrid, Madrid, Spain 92 Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil 93 Department of Respiratory Medicine, University Hospital Olomouc, Olomouc, Czech Republic 94 Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Salerno, Italy 95 Department of Respiratory Medicine, Copenhagen University Hospital-­Hvidovre, and Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 96 Health Planning Unit, Department of Social Medicine, Faculty of Medicine, University of Crete, Greece and International Primary Care Respiratory Group IPCRG, Aberdeen, Scotland 97 Pneumology and Allergy Department CIBERES and Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, University of Barcelona, Barcelona, Spain 98 Vilnius University Faculty of Medicine, Institute of Clinical Medicine & Institute of Health Sciences, Vilnius, Lithuania 99 European Academy of Paediatrics (EAP/UEMS-­SP), Brussels, Belgium 4 | HAGEMANN et al. 100 Department of Lung Diseases and Clinical Immunology, University of Turku and Terveystalo allergy clinic, Turku, Finland 101 Filha, Finnish Lung Health Association, Helsinki, Finland 102 University of Turku, Turku, Finland 103 University of Bari Medical School, Unit of Geriatric Immunoallergology, Bari, Italy 104 Nova Southeastern University, Fort Lauderdale, FL, USA 105 Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 106 Celal Bayar University Department of Pulmonology, Manisa, Turkey 107 The Allergy and Asthma Institute, Pakistan, Pakistan 108 Universidad Católica de Córdoba, Universidad Nacional de Villa Maria, Córdoba, Argentina 109 University Hospital Montpellier, Montpellier, France 110 Center for Rhinology and Allergology, Wiesbaden, Germany Correspondence Jean Bousquet, Charité Abstract Universitätsmedizin Berlin, corporate Background: Although there are many asymptomatic patients, one of the problems of member of Freie Universität Berlin, Humboldt-­Universität zu Berlin, and COVID-­19 is early recognition of the disease. COVID-­19 symptoms are polymorphic Berlin Institute of Health, Comprehensive and may include upper respiratory symptoms. However, COVID-­19 symptoms may Allergy Center, Department of Dermatology and Allergy, Berlin, Germany be mistaken with the common cold or allergic rhinitis. An ARIA-­E AACI study group Email: jean.bousquet@orange.fr 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 symp- toms of COVID-­19, common cold and allergic rhinitis. Results: Among the 192 ARIA members who were invited to respond to the question- naire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-­way ANOVA revealed significant differences in the symptom inten- sity 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. KEYWORDS allergic rhinitis, common cold, cough, COVID-­19, smell 1 | I NTRO D U C TI O N COVID-­19 symptoms are polymorphic. Typically, COVID-­19 induces shortness of breath, cough, fever, nasal congestion and Although there are many asymptomatic patients, one of the general malaise.3 However, SARS-­coronavirus-­2 (SARS-­CoV-­2) in- problems of COVID-­19 is early recognition of the disease. Pre-­ fection has been linked to a number of other symptoms afflicting medical visit screening and symptom evaluation have to be im- several organ systems, including muscle and joint pain, sore throat, plemented quickly to minimise the risk of seeing COVID-­19 headache, nausea, vomiting and diarrhoea, as well as coagulopa- patients unprepared. Furthermore, testing for coronavirus is still thy.4 Impaired sense of smell and taste has emerged as an alarming widely restricted due to the shortage of available PCR tests in symptom of SARS-­CoV-­2 infection in the West, but not so much in many countries.1 Testing capacities have improved dramatically Asia.5–­9 Presentation in the upper respiratory tract has also been de- since the beginning of the pandemic, with the recent addition of scribed as extremely variable across age groups,10 making it difficult antigen-­b ased testing. Some of these tests are home-­b ased and to distinguish COVID-­19 from common upper respiratory infections have only just obtained FDA approval. However, they still repre- (e.g. croup in children10). 2 sent a bottleneck, with the subsequent waiting periods leading Therefore, besides the management of severe COVID-­19, one of to large groups of people at risk of infection requiring quarantine. the major problems of the infection is how to screen citizens with To prevent unnecessary closure of critical facilities, for example possible COVID-­19 and distinguish them from patients with simi- schools and public services, triage requires further improvement lar symptoms caused by allergic rhinitis11,12 or other common viral in terms of speed and accuracy. infections of the respiratory tract. A digital tool enabling a rapid TA B L E 1 The original survey with 15 items COVID−19 Common cold Allergic rhinitis Max Max Max Level VAS VAS VAS Agreement HAGEMANN et al. Question Occurrence Characteristics (mean) SD Occurrence Characteristics (mean) SD Occurrence Characteristics (mean) SD MEAN SD 1 Runny nose Very rare If present, mild 3.98 0.15 Always Anterior and 9.93 0.54 Often Profuse 5.41 1.22 8.50 1.90 (anterior symptoms posterior anterior rhinorrhea) (VAS<5/10) rhinorrhea rhinorrhea 2 Sneezing Very rare Not in bursts 3.99 0.11 Common Not in burst 5.02 0.21 Very In burst 9.99 0.11 9.37 1.09 common 3 Stuffy nose Not If present, mild 4.10 0.68 Always Often severe 10.00 0.00 Very May be severe 8.07 0.36 8.86 1.51 uncommon symptoms common (VAS<5/10) 4 Nasal pruritus NO 0.00 0.00 NO 0.08 0.53 Very Variable in 8.02 0.21 9.22 1.38 common intensity 5 Nasal pain Possible 2.99 0.11 Sometimes 3.00 0.00 NO 0.00 0.00 8.21 2.22 6 Ocular itch NO 2.94 0.38 NO 3.00 0.00 Common 10.00 0.00 9.31 1.41 7 Ocular pain Possible 3.09 0.78 3.00 0.00 NO 0.06 0.53 8.14 2.43 8 Ocular redness Possible 3.07 0.54 NO 3.05 0.30 Common 9.98 0.21 8.36 2.29 9 ≥3 nasal NO N/A YES N/A YES N/A 8.92 1.82 symptoms 10 Smell Not Usually anosmia whereas 10.00 0.00 Sometimes 6.98 0.21 Rare Anosmia very 6.95 0.30 8.88 1.88 dysfunction uncommon in other diseases seldom it is hyposmia. Associated with other COVID−19 symptoms, it is likely to be a significant diagnostic criterion 11 Taste Not Dysgeusia rather 10.00 0.00 Rare 3.00 0.00 Very rare 2.00 0.00 9.24 1.34 dysfunction uncommon than loss of taste. Associated with other COVID−19 symptoms, it is likely to be a significant diagnostic criterion 12 Dyspnea Relatively May start as an isolated 10.00 0.00 Rare 5.00 2.92 Sometimes 10.00 0.00 9.08 1.35 common mild symptom if but may rapidly asthma become severe with respiratory rate>24/ | min 5 6 | HAGEMANN et al. distinction is needed for this approach and may be of great impor- 1.22 1.66 1.73 SD tance during the winter with the co-­existence of COVID-­19, flu, Agreement common cold or other respiratory viral infections and house dust MEAN mite-­induced rhinitis. Level 8.84 8.77 9.22 Systematic reviews and meta-­analyses have been produced for many COVID-­19 symptoms including differentiation between flu 0.00 0.00 2.87 and COVID-­19.13 However, there is insufficient knowledge on con- SD sensus across the international medical community regarding nasal (mean) 10.00 10.00 4.33 Max VAS symptoms that may enable differentiation between COVID-­19, common cold and allergic rhinitis. An ARIA (Allergic Rhinitis and Characteristics its Impact on Asthma)-­E AACI (European Academy of Allergy and Clinical Immunology)-­GA 2LEN (Global Allergy and Asthma European Network) initiative was carried out to establish consensus on a set of questions aimed at distinguishing these diseases. From this con- Allergic rhinitis sensus, an algorithm will be proposed and digitalised using a method Occurrence Sometimes Sometimes asthma asthma already validated in MASK.14–­16 The current paper presents the re- sults of the consensus. if if Rare This is a new paper of the series of ARIA-­E AACI papers on COVID-­19.17–­21 2.06 1.09 1.12 (mean)SD 8.25 3.50 Max 7.60 VAS 2 | M E TH O D S Characteristics symptoms A modified Delphi was carried out. 22 A questionnaire developed Follows the by JB, WC, LK and JM was sent to all ARIA members by GLO. nasal Those seeing COVID-­19 patients were requested to answer within a week. Common cold The questionnaire included items related to upper and lower Occurrence Common Common airway symptoms for COVID-­19, common cold and allergic rhinitis Rare (Table 1). In the questionnaire, the respondents were asked to assess five nasal symptoms, three ocular symptoms, taste, smell, cough, 0.00 0.62 0.11 wheezing and sore throat. For each question, there was a statement SD on frequency and severity. For this, participants were asked to grade (mean) the severity from 0 to 10. Then, they gave a global assessment from 10.00 5.09 Max 4.99 VAS 0 to 10 according to whether they agreed on the suggested severity grading for the three diseases. A level of 6 or higher was considered May start as an isolated contradistinction to cough per hour) but mild symptom (2–­4 as agreement. Suggestions for questions/statements were able to be rapidly becomes episodes of dry added to the questionnaire. not severe in Characteristics Rarely isolated, A total of 87 answer sheets were included in this analysis. Any asthma written comments were transformed into numeric changes where severe possible. To determine whether the participants agreed that the symptom/item was to be included in the tool, we collected the total number of participants agreeing as well as the total percentages. uncommon uncommon The same procedure was used for disagreement and missing/invalid common Occurrence COVID−19 Relatively data, respectively. Not Not 3 | R E S U LT S Sore throat Wheezing Among the 192 questionnaires sent out, 89 (46.3%) were returned Cough Question within 7 days. The average monthly number of COVID-­19 consulta- tions among the participants was 16.8 ± 20. The participants were 15 13 14 from 37 different countries (Figure 1). HAGEMANN et al. | 7 F I G U R E 1 Countries involved in the questionnaire TA B L E 2 Participants' agreement to Missing/invalid the questionnaire items Disagree (≤6) Agree (>6) answer n = 87 No. Symptom n % n % n % 1 Runny nose (anterior 12 13.8 62 71.3 13 14.9 rhinorrhea) 2 Sneezing 3 3.4 72 82.8 12 13.8 3 Stuffy nose 8 9.2 68 78.2 11 12.6 4 Nasal pruritus 7 8.0 69 79.3 11 12.6 5 Nasal pain 14 16.1 61 70.1 12 13.8 6 Ocular itch 5 5.7 70 80.5 12 13.8 7 Ocular pain 16 18.4 60 69.0 11 12.6 8 Ocular redness 13 14.9 62 71.3 12 13.8 9 ≥3 Nasal symptoms 7 8.0 65 74.7 15 17.2 10 Smell dysfunction 8 9.2 67 77.0 12 13.8 11 Taste dysfunction 2 2.3 73 83.9 12 13.8 12 Dyspnea 5 5.7 67 77.0 15 17.2 13 Cough 4 4.6 69 79.3 14 16.1 14 Wheezing 7 8.0 64 73.6 16 18.4 15 Sore throat 8 9.2 67 77.0 12 13.8 Mean 9.1 76.3 14.6 There was a high proportion of agreeing participants, with an in Figure 2. A two-­way ANOVA revealed significant differences in average of 76.3% (range 69–­83). The overall data quality was accept- symptom intensity between the three diseases (p < .001). able, and missing values for some of the questions were below 20% Eye symptoms (7, 8) were among the most discussed statements, (Table 2). and the corresponding statements had relatively low levels of ap- Participants were able to grade the maximum expected severity proval (Figure 1). Nasal pain (5) was regarded as impractical by six for each disease, and the average final VAS severity data are shown participants, which was also reflected by a relatively low level of 8 | HAGEMANN et al. F I G U R E 2 Maximum expected 1 Runny nose (anterior rhinorrhea) symptom severity. Analogue scale from COVID-19 0 (not present) to 10 (maximum severity). 2 Sneezing Means ± SD are shown. A two-­way 3 Stuffy nose Common cold ANOVA revealed significant differences in VAS between diseases (p < .001) 4 Nasal pruritus Allergic rhinitis 5 Nasal pain 6 Ocular itch 7 Ocular pain 8 Ocular redness 10 Smell dysfunction 11 Taste dysfunction p<0.0001 12 Dyspnea 13 Cough 14 Wheezing 15 Sore throat 0 2 4 6 8 10 analogue scale TA B L E 3 Additional items to be integrated in the algorithm 1 Runny nose 2 Sneezing Strenuous fatigue Fever 3 Stuffy nose COVID−19 comorbidities 4 Nasal pruritus Contact with COVID patient 5 Nasal pain Travel to ‘high-­risk’ region 6 Ocular itch Gastrointestinal symptoms 7 Ocular pain Muscle/body ache 8 Ocular redness Profound sweating 10 Smell dysfunction 11 Taste dysfunction 4 | DISCUSSION 12 Dyspnea This paper presents the results of a consensus initiative across the 13 Cough ARIA network of health professionals. The aim was to develop a set 14 Wheezing of questions on symptoms and their intensity in order to discrimi- 15 Sore throat nate between classical rhinologic disorders and COVID-­19. The pres- entation of COVID-­19 is highly variable, ranging from a complete 0 5 10 absence of symptoms to severe illness and critical organ dysfunc- Level of agreement 0 to 10 tion. The underlying mechanisms for this polymorphic behaviour are yet to be defined. F I G U R E 3 Mean level of agreement to suggested symptom Within the ARIA network of specialists in upper and lower re- severity. Analogue scale rating with range from 0 (disagreement) to 10 (complete agreement). A level of 6 or higher was considered as spiratory diseases, we asked 193 to respond to our consensus initia- ‘agreement’. Means ± SD are shown tive, of whom 89 did. The response rate was under 50%, but many physicians were not seeing COVID-­19 patients. The strength of this agreement (8.21 ± 2.2; Figure 3). This was possibly caused by differ- paper is that the involved participants represented different medical ent interpretations of the item's description, and this issue needs to specialties and many different countries, suggesting a generalisation be addressed in further developments of the algorithm. of the study. Additional common COVID-­19 symptoms will be considered for We found high levels of consensus among this community, with integration in the future algorithm development process (Table 3). over 76% of participants agreeing to the symptoms presented in our HAGEMANN et al. | 9 questionnaire. VAS was found to be a useful and simple tool for dis- Smith-­Kline, advisory role in Scibase. JB reports personal fees from cussing questions of symptom intensity in this large group of health Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, professionals. Statistical analysis revealed a significantly different Purina, Sanofi-­Aventis, Takeda, Teva, Uriach, other from KYomed-­ expected maximum VAS of the three diseases (two-­way ANOVA, Innov. VC reports personal fees from ALK, Allergy Therapeutics, p < .001). Hence, there are potential symptom constellations that LETI, Thermofisher, Merck, Astrazeneca, GSK. JCS reports Advisory allow discrimination between the three diseases. Board from Boheringer Ingelheim, personal fees and Advisory Board The triage of patients with newly developed symptoms –­ any from GSK, Bial, grants, personal fees and Advisory Board from individual under suspicion of being at risk of SARS-­CoV-­2 infection –­ AstraZeneca, non-­financial support from Mundipharma, personal remains a challenge during this pandemic. Digital application-­based fees from Sanofi, Advisory Board from Novartis. JCI reports per- symptom reporting and triage have been evaluated in prospective sonal fees from Faes Farma, Abbott Ecuador, Laboratorios Casasco, trials in the UK, China and the US. 23–­25 The improvement of triage Laboratorios Bago Bolivia, Eurofarma Argentina, Sanofi. PK reports will also (i) enhance pre-­test probability for SARS-­CoV-­2 PCR swabs personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, or alternative test methods; (ii) increase the availability of tests in Boehringer Ingelheim, Hal Allergy, Lekam, Mylan, Novartis, general to make current infection numbers more accurate; (iii) ease Polpharma, Sanofi, Teva, Chiesi, USP Pharmacia. VK reports personal unnecessary quarantine; and (iv) reduce the closure of schools, child fees from GSK, non-­financial support from AstraZeneca, DIMUNA, day care and public services. DLL reports personal fees from Allakos, Amstrong, Astrazeneca, ARIA-­MASK includes a decision-­making tool for allergic rhini- Boehringer Ingelheim, Chiesi, DBV Technologies, Grunenthal, GSK, 14 tis. With a broad user base of 39,670, there is an opportunity to MEDA, Menarini, MSD, Novartis, Pfizer, Novartis, Sanofi, Siegfried, provide newly developed tools for a large group of patients. The UCB, Alakos, Gossamer, grants from Sanofi, Astrazeneca, Novartis, questionnaire, along with the participants’ comments, has to be UCB, GSK, TEVA, Boehringer Ingelheim, Chiesi, Purina institute. BL transferred to a validation process. This process can be enhanced reports grants and personal fees from Mylan, Glenmark. JM reports by already-­developed artificial intelligence (AI) in order to fine-­ personal fees and other from SANOFI-­GENZYME & REGENERON, tune and improve symptom VAS thresholds. A final questionnaire NOVARTIS, ALLAKOS, grants and personal fees from MYLAN-­MEDA and algorithm are open for use across the medical community, fo- Pharma, URIACH Group, personal fees from MITSUBISHI-­TANABE, cussing on specialists treating upper and lower airway diseases and MENARINI, UCB, ASTRAZENECA, personal fees from GSK, MSD. allergy, hence confronted with similar rhinologic, pneumologic and NP reports personal fees from Novartis, Nutricia, HAL, MENARINI/ ophthalmologic symptoms. For allergy and respiratory tract spe- FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, cialists, undoubtedly at high risk of infection during examinations, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from recommendations for treatment and handling of the field of allergic Gerolymatos International SA, Capricare. OP reports grants and diseases have been suggested by the European Academy of Allergy personal fees from ALK-­Abelló, Allergopharma, Stallergenes Greer, and Clinical Immunology (EAACI) in alliance with the global initia- HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie tive ‘Allergic Rhinitis and its Impact on Asthma’ (ARIA).17,19–­21,26 It GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., has been shown that digital decision-­making tools and app-­based Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, algorithms can improve patient–­doctor communication and therapy personal fees Astellas Pharma Global, EUFOREA, ROXALL Medizin, adherence for both patients and physicians. 27,28 Novartis, Sanofi-­Aventis and Sanofi-­Genzyme, Med Update Europe In summary, our future COVID-­19 symptom tool may be a help- GmbH, streamedup! GmbH, grants from Pohl-­Boskamp, Inmunotek ful device for improving active patient reporting and triage of pa- S.L.,personal fees from John Wiley and Sons, AS, personal fees tients when integrated in the ARIA MASK-­air App. We have asked from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA 2LEN the networks to circulate the tool to their members for testing, and Partner), Indoor Biotechnologies. DP reports grants and personal we hope to be able to present the results and create more robust fees from GlaxoSmithKline, personal fees from Menarini, Pliva, evidence in its practicality. This article presents a substantial con- Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, AbbVie, Novartis, sensus effort in COVID-­19-­treating physicians across the globe. MSD, Chiesi, Revenio, non-­financial support from Philips, personal Limitations arise from missing or inappropriate data in the returned fees and non-­financial support from Boehringer Ingelheim, FP re- questionnaires. However, the development process is followed by ports personal fees from SANOFI, ASTRAZENECA, NOVARTIS, AI-­supported validation, and future studies have to show the power GLAXO SMITHKLINE, STALLERGENES, ALLERGY THERAPEUTICS, of such questionnaires. HAL ALLERGY, MENARINI, MALESCI, GUIDOTTI, VALEAS, BOEHRINGER INGELHEIM, ALMIRALL, MUNDIPHARMA. NR re- C O N FL I C T S O F I N T E R E S T ports and Advisory Board: Sanofi, Mylan, AstraZeneca, Speaker: CA reports grants from Allergopharma, Idorsia, Swiss National Sanofi, Mylan, Chiesi. JS reports grants and personal fees from Science Foundation, Christine Kühne-­Center for Allergy Research SANOFI, personal fees from GSK, NOVARTIS, ASTRA ZENECA, and Education, European Commission's Horison's 2020 Framework MUNDIPHARMA, FAES FARMA. Dr. Tsiligianni reports grants from Programme, Cure, Novartis Research Institutes, Astra Zeneca, GSK Hellas, ELPEN, Astra Zeneca Hellas, personal fees from GSK, Scibase, advisory role in Sanofi/Regeneron, grants from Glakso Boehringer Ingelheim, Novartis, Astra Zeneca. DW reports personal 10 | HAGEMANN et al. 3. Mair M, Singhavi H, Pai A, et al. A meta-­analysis of 67 studies with fees from Optinose, ALK, Sanofi, and was co-­chair of Joint Task Force presenting symptoms and laboratory tests of COVID-­19 patients. on Practice Parameters until July 2020. author of Rhinitis GRADE Laryngoscope. 2020. https://doi.org/10.1002/lary.29207 document (2017) and Rhinitis practice parameter update (2020). 4. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of covid-­19 in New York City. N Engl J Med. 2020;382(24):2372-­2374. TZ reports personal fees from Bayer Health Care, FAES, Novartis, 5. 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Sharon Chinthrajah, Tomas Chivato, Ekaterine Chkhartishvili, George Christoff, Henry Chrystyn, Derek K Chu, Antonio Chua, Alexander Chuchalin, Kian Fan Chung, Alberto Cicerán, Cemal Cingi, Giorgio S U P P O R T I N G I N FO R M AT I O N Ciprandi, Ieva Cirule, Ana-­C arla Coelho, Enrico Compalati, Jannis Additional supporting information may be found online in the Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David Supporting Information section. Costa, María del Carmen Costa Domínguez, André Coste, M. Cottini, Linda Cox, Carlos Crisci, Maria Angiola Crivellaro, Alvaro A Cruz, John Cullen, Adnan Custovic, Biljana Cvetkovski, Wienczyslawa How to cite this article: Hagemann J, Onorato GL, Jutel M, et Czarlewski, Gennaro D'Amato, Jane da Silva, Ronald Dahl, Sven-­Erik al. Differentiation of COVID-­19 signs and symptoms from Dahlen, Vasilis Daniilidis, Louei Darjazini Nahhas, Ulf Darsow, Janet allergic rhinitis and common cold: An ARIA-­E AACI-­GA LEN 2 Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-­Ricardo consensus. Allergy. 2021;00:1–13. https://doi.org/10.1111/ de la Torre Navarrete, Chato de los Santos, Esteban De Manuel all.14815 Keenoy, Govert De Vries, Diana Deleanu, Pascal Demoly, Judah Denburg, Philippe Devillier, Alain Didier, Sanja Dimic Janjic, Maria Dimou, Anh Tuan Dinh-­Xuan, Ratko Djukanovic, Maria Do Ceu APPENDIX 1 Texeira, Dejan Dokic, Margarita Gabriela Domínguez Silva, Habib ARIA MEMBER LIST Douagui, Nikolaos Douladiris, Maria Doulaptsi, Gérard Dray, Ruta Amir Hamzah Abdul Latiff, Baharudin Abdullah, Werner Aberer, Dubakiene, Eve Mathieu-­Dupas, Stephen Durham, Marzia Duse, Nancy Abusada, Ian Adcock, Alejandro Afani, Ioana Agache, Xenofon Mark Dykewicz, Didier Ebo, Natalija Edelbaher, Thomas Eiwegger, Aggelidis, Jenifer Agustin, Cezmi A Akdis, Mübeccel Akdis, Mona Al-­ Patrik Eklund, Yehia El-­Gamal✝, Zeinab A. El-­Sayed, Shereen S. 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