Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. fCVD1 a atclrylw ihhge rvlneo ID scmriiy ugsigta ID ih earisk a be might NIDDM that incidence suggesting comorbidity, the as asthmatics, asthmatics. severe NIDDM severe of of in cohort prevalence COVID-19 large higher our for compared with In factor (71%) low, CONCLUSIONS: higher particularly was (29%). was vs agents anti-IgE COVID-19 biologic (15.4% with anti-IL5 of not treated of (NIDDM) treated patients did mellitus worsening those of who of diabetes number experienced those the proportion non-insulin-dependent patients to to the of patients infected compared prevalence COVID-19 COVID-19, of higher among by significantly p=0.002); (34.6%) affected 3.8%, a Nine asthmatics had Severe asthmatics infection, COVID-19. severe the period. 1504 with contracted their symptomatic of suspect describing COVID-19 In out Italy, the highly (1.73%) in METHODS:: during Twenty-six or of asthmatics asthma RESULTS: severe patients. incidence confirmed of disease. of the as population COVID-19 subgroup about identified large of this a far, were course in in so clinical cases outcomes available, and COVID-19 COVID-19 characteristics is of epidemiological the clinical incidence data first are the No the investigated which to we about study, under-reported. theoretically according and this however, are and asthmatics SARS-CoV-2; diseases potentially severe by pulmonary disease in infected chronic 2020. lung COVID-19 if far, February obstructive ill so since chronic seriously published therefore world and studies and entire asthma vulnerable as the more such almost be diseases, affecting may pulmonary is chronic pandemic with (COVID-19) Patients 19 Disease COronaVIrus BACKGROUND: Abstract 2020 24, June 15 Milan 14 13 12 11 10 9 8 7 6 5 4 3 2 1 Senna Padovani Malipiero Giacomo Heffler treatments Enrico and comorbidities patients: of (SANI) impact Italy features, in clinical Network Asthma Severe in COVID-19 zed seair rc al Cuneo Carle e Croce infrastructure S (SANI) Ospedaliera Emanuele” Italy Azienda Vittorio in - Network ”Policlinico Asthma AOU Severe - Catania Mauriziano of AO University & Torino IRCCS of Hospital, University Research and Clinical Center Humanitas Research and Clinical Humanitas Ferrara of University University Humanitas zed seair nvriai eeioI,Npe,Italy Naples, II, Federico Universitaria Ospedaliera Azienda uaia lncladRsac Center Research and Clinical C`aHumanitas Granda, Maggiore Ospedale Fondazione IRCCS Milano, di Studi Universit`a degli Pisa of University Hospital University Verona Milan srl of Tech University Tourbillon Engineering Management 2. 12 irug Paggiaro Pierluigi , 3 ispeGuida Giuseppe , 1 aeiaDetoraki Caterina , 5 us Brussino Luisa , 13 9 let ivniGerli Giovanni Alberto , rnec Blasi Francesco , 2 ac Contoli Marco , 6 lui Crimi Claudia , 1 14 n iri atrCanonica Walter Giorgio and , 3 let Papi Alberto , 7 10 ail Morrone Daniela , tfn centanni stefano , 3 ivniPaoletti Giovanni , 8 11 Marianna , Gianenrico , 15 4 , Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. a:+3 0282246484 39 + Fax: 0282247013 +39 Tel: Italy – (MI) Rozzano – 20089 56 Manzoni Alessandro Via Humanitas Clinico Istituto Allergy and Asthma Medicine, Personalized Heffler Scichilone Enrico MC. P., Prof. Zappa Santus MR., G., Yacoub Rolla V., G., E., Menzella Pelaia Viviano Author: Ridolo F., V., A., L., Corresponding Patella Vianello Mazza Richeldi G., G., FLM., L., Passalacqua Spadaro Ricciardolo Macchia R., P., L., Parente C., Solidoro Ricciardi E., Farsi Lombardi N., F., Nucera S., S., Puggioni Giacco M., Cicero L., Montagni Del P., Lo Pini M., Montuschi D’Amato G., D’Al`o M., S., Guarnieri N., Milanese BMP., Crimi F., Foschino MT., Costantino E., Favero L., Cosmi A., AG., Corsico ME., Conte * Italy. Milano, 14 - Policlinico Maggiore Ospedale C`a Granda 13 12 Italy. 11 Milano, - Milano of University 10 9 8 7 6 5 Italy. 4 Napoli, II, Federico Universitaria Ospedaliera 3 2 Italy (MI), 1 Blasi Gerli Giovanni Alberto Malipiero of real-life Heffler in impact Enrico asthma features, severe and clinical COVID-19 patients: title: (SANI) Short Italy in treatments Network and Asthma comorbidities Severe in COVID-19 eateto nenlMdcn,Ciia muooy lnclPtooyadIfciu ies,Azienda Disease, Infectious and Pathology Clinical Immunology, Clinical Medicine, Internal of Department eateto eia cecs OOdn arzaoUbroI–Uiest fTrn oio Italy. Torino, - Torino of University – I Umberto Mauriziano Ordine AO Sciences, Medical of Department leg n nuooyUi ..S rc al ue,Italy. Italy. Cuneo, Padova, – - Carle srl e Tech Tourbillon Croce Engineering S. Management A.O. - Italy Unit Milano, Pneumology – and Italy. infrastructure Allergy Catania, (SANI) - Italy Catania in of Network University Asthma - Severe Medicine Experimental and Clinical Italy. of Ferrara, Department – Ferrara of University - Medicine Experimental and Surgery Morphology, of Department Italy (MI), Emanuele Pieve – University Humanitas – Sciences Biomedical of Department esnlzdMdcn,Atm n leg uaia lncladRsac etrICS-Rozzano - IRCCS Center Research and Clinical Humanitas - Allergy and Asthma Medicine, Personalized AIWrigGop oai . uc . aaaM. aars . aiitoiG,Crs C., Caruso G., Camiciottoli C., Calabrese MF., Caiaffa C., Bucca M., Bonavia Group: Working SANI nenlMdcn eatet–RsiaoyUi n dl ytcFboi etr–Fnain IRCCS Fondazione – Center Fibrosis Cystic Adult and Unit Respiratory – Department Medicine Internal eateto ahpyilg n rnpatto nvriyo iao–Mln,Italy Milano, – Milano of University – Transplantation and Pathophysiology of Italy.Department Pisa, - Pisa of University - Care Critical and Italy. Biology Verona, Molecular - Medicine, Hospital Surgery, University of Verona Department - Unit Allergy and Center Asthma eprtr nt STSniPooeCro a al optl eateto elhSine – Sciences Health of Department Hospital, Paolo San Carlo, e Paolo Santi ASST Unit, Respiratory 13,14 iri atrCanonica Walter Giorgio ; 1 us Brussino Luisa ; 1,2 iaeiiDetoraki Aikaterini ; 9 tfn Centanni Stefano ; 5 lui Crimi Claudia ; 1,2 nbhl fSN okn Group Working SANI of behalf on 3 ac Contoli Marco ; 6 ail Morrone Daniela ; 10 innioSenna Gianenrico ; 2 4 let Papi Alberto ; 7 ainaPadovani Marianna ; 11 irug Paggiaro Pierluigi ; 4 ivniPaoletti Giovanni ; * 4 ispeGuida Giuseppe ; 12 1,2 Francesco ; Giacomo ; 8 ; Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. ftebgetpneiso h atcnuis OI-9ciia aiettossetu agsfo mild from ranges spectrum manifestations clinical COVID-19 centuries. last the of of deaths pandemics number 34000 biggest increasing 2020 than Re- the ever more 19th, Acute of an in June Severe resulted to reported confirmed and updated 200,000 has over (data subjects Country, reached infected Asian has (SARS-CoV-2) non- which Syndrome-Coronavirus-2 first patients, spiratory Italy, (COVID-19) 19 2020 Disease February COronaVIrus of end the Since managing in work invaluable the INTRODUCTION for staff SANI the TEXT: & MAIN Sirena Concetta Rabotti, network. Silvia the to grateful Kline, are Smith We Glaxo AstraZeneca, by grants Aknowledgements unrestricted through Genzyme Sanofi supported & is Novartis SANI statement: Funding statements: interest of Conflict Email: • • • • • • • • • • • • • • • • • eeo,SnfiAets ao-ezm,SalreeGer C hra rahPam,Valeas, Pharma, Re- Uriach Novartis, pharma, Menarini, Mundipharma, A. UCB Merck, from: Mylan, StallergenesGreer, ViborPharma Allergy, fees Genen- Sanofi-Genzyme, Hal board Farmaceutici, Sanofi-Aventis, Kline, advisory Chiesi generon, Smith or Glaxo Boehringer-Ingelheim, lecture Guidotti-Malesci, AstraZeneca, as tech, and well Therapeutics, Novartis as Allergy Mundipharma, grants Insmed, Menarini, Alk-Abello, reports and Grifols, Canonica Pfizer Guidotti, Walter GSK, work from Giorgio submitted Chiesi, fees the Astrazeneca, personal outside from Zambon, and fees Bayer, work personal from submitted and and grants the grants Sanofi, outside and reports Novartis Mundipharma, Blasi Chiesi, Guidotti, Francesco AstraZeneca, GlaxoSmithKline, from report from fees to fees personal interest personal and of grants conflict reports any Paggiaro have Pierluigi not VALEAS, does ZENECA, work Senna ASTRA submitted SPA, Gianenrico the CHIESI SPA, from outside MENARINI fees INGELHEIM, NOVARTIS, personal BOEHRINGER GLAXOSMITHKLINE, report and grants to from and interest fees MALESCI, of GUIDOTTI personal conflict report reports any to have Centanni interest not Stefano of does conflict report Gerli any to Giovanni have interest Alberto not of report does conflict to Guida any interest have Giuseppe of not conflict does any Padovani have Marianna not Menarini. report does from to Morrone interest fees Daniela of personal report conflict reports to any Crimi interest have Claudia of not conflict report does any to Brussino have interest Luisa not of does conflict Malipiero any have Giacomo work. Fonda- not submitted from does the grants Paoletti outside Giovanni Edmondpharma, Mundipharma, Chiesi, Roche, GlaxoSmithKline, Fondazione Farma- from from Maugeri, Chiesi fees other zione Ingelheim, personal and Boehringer Sanofi/Regeneron, support from Novartis, Mena- non-financial other Zambon, AstraZeneca, fees, and from personal support support TEVA, non-financial non-financial ceutici, fees, and fees personal personal grants, grants, rini, grants, reports Papi Alberto submitted Astra- the Chiesi, outside from Zambon, fees Novartis, work personal GlaxoSmithKline, Italy, Alk-Abello, report – Ferrara Ingelheim, to of Sanofi, Boehringer University interest Zeneca, Chiesi, AstraZeneca, of from grants conflict from work; reports any submitted fees Contoli have Marco the personal not outside does and Valeas, Detoraki Ingheleim, boards Aikaterini Boheringer advisory Nestl`e Purina, Circassia, to Novartis, participation GSK, reports Heffler Enrico enrico.heffl[email protected] : 1 .TeSR-o- neto a pedaloe h ol eoigone becoming world the over all spread has infection SARS-CoV-2 The ). 3 Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. e ulse yteEetv elhCr rga fteAec o elhaeRsac n Quality and outco- Research patient Healthcare evaluating for regis- for Agency SANI registries the The of on Oviedo. Program Recommendation and Care Edition Helsinki Health 3rd Effective of the the declarations to by the according published to up mes according set out was regions. carried try administrative was by observatory divided The cases website Government of number Italian the the representing of ISSUES: map ETHICAL Department thematic general Protection Italian a the Civil draw in the to subjects used from infected SARS-CoV-2 and collected of cases been confirmed have of number population the about data access Open ITALY: cases Italy). IN all COVID-19 Ferrara, for ON collected Ferrara, INFORMATION platform been di GENERAL registry have all course Univeristaria the and clinical from Ospedaliero study and obtained treatment (Azienda the been symptoms, reported. Center in have COVID-19 enrolled COVID-19, additional about asthmatics data of the Additional severe cases from of suspect collected population or and entire confirmed the of cases of reported data asthma. clinical severe and lung of and Demographic because cohorts findings specimens their swab swab laboratory oropharyngeal among oropharyngeal symptoms, or contingencies/emergency) or nasopharyngeal with to clinical nasopharyngeal patients access of without (i.e. of but COVID-19 analysis COVID-19 of of from typical cases SARS-CoV-2 imaging suspect virus highly the or for specimens) result test positive with Society territory Thoracic (ERS)/American national Society data Respiratory biomarkers European classification to inflammatory according (ATS) functional, asthma clinical, severe demographic, with patients collecting of observatory web-based a is SANI to aimed also PATIENTS: we Italy); disease. the worldwide Ferrara, COVID-19 of asthma Ferrara, of population severe course di METHODS: the for clinical Univeristaria in and registry characteristics infection Ospedaliero largest clinical COVID-19 (Azienda the their of of Center describe incidence one additional the (SANI), investigate an Italy to clinical in in was collect Network asthmatics. study in rapidly Asthma severe this Severe of infection to the populations the of opportunity large the of aim unique on on outcomes The COVID-19 a available clinical of is are the impact the on data observatories on and No registry-based information severe infection infection. Real-life, considered COVID-19 SARS-CoV-2 patients. are to to these asthmatics these vulnerability severe (OCS): increased of corticosteroids expect susceptibility oral would of experience one to use patients, combination continue chronic in population, patients and/or (ICS) asthma corticosteroids drugs asthma inhaled entire controller high-dose of other with 5-10% 2.5% treatment with despite to about exacerbations not 0.3 accounting and from are asthmatics, symptoms ranging diseases of patients, pulmonary COVID-19 proportion chronic in A far, conditions so clinical published common studies most the epidemiological amongst the response immune to antiviral according impaired with Nonetheless, associated is patients, risk asthmatic increased of including 6 proportion asthma, large with a patients characterizes in episodes outcomes exacerbation adverse are asthma severe (COPD), of with disease associated lung are obstructive infection infections chronic SARS-CoV-2 viral by and by asthma affected as severely more such potentially diseases, pulmonary chronic subjects with dysfunction, patientsPatients infected multiorgan hospitalized of of or 7% third shock, about one of failure, about population respiratory in pneumonia, death interstitial to leading diffused including critical, to n rae xrsini iwyeihla el fmlclsascaewt ASCV2infectivity SARS-CoV-2 with associate molecules of cells epithelial airway in expression greater a and 11 12,13 ie h eagdimnlgclrsosvns htcaatrzssvr asthma severe characterizes that responsiveness immunological deranged the Given . 11 l etr,hv encnatdadiqie orpr ofimd(..patients (i.e. confirmed report to inquired and contacted been have centers, All . n aged and 5 > nadto,i a ensgetdta ye2imnlgcpol,which profile, immunologic 2 type that suggested been has it addition, In . 2yas erie yaceie etr ooeeul pedotthe out spread homogeneously centers accredited by recruited years, 12 3 . 4 2 ihaoealcs-aaiyrt ntegeneral the in rate case-fatality overall a with 4 ned ti eletbihdta respiratory that established well is it Indeed, . 8-10 12,13 . and , 1 7 , . Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. nte osbeepaainsad nteitiscfaue ftp- namto,ta hrceie a characterizes that inflammation, type-2 of features intrinsic the in stands explanation pandemic COVID-19 possible the Another during therapy recent inhalation could Indeed, to they medications. patients adherence asthma therefore asthma in taking and among increase regularly in significant exacerbations, applying careful a first, constantly for more lockdown, report the being trigger and publications and is distancing prevention, a Self-containment of social as rules respecting this. hygiene acting scrupulously the for and caution, infections reasons infection greater virus different with SARS-CoV-2 of acted the potentially have awareness of Italy are risk in the There high (14.5% of at COVID-19. population not because of are general forms asthma the severe severe in with the of as patients rate that under-reported mortality support suggest COVID-19 is findings not the asthma these which (7.7%) does lower in finding infection is patients, COVID-19 SARS-COV2 that This on to infrequent. data condition was epidemiological susceptible comorbidity large COVID-19 particularly published asthmatics, a first severe as the asthma of of cohort concept large our In COVID-19. patients 26 the population). IgE of study anti characteristics our DISCUSSION on clinical in were and omalizumab (29%) demographic with 6 summarizes whilst treated I population) the asthmatics Table 15 study severe for our counting all (n=21), in - of anti-IL5 COVID-19 n=2 1.3% with Benralizumab experiencing - treated 13; (Omalizumab asthmatics and n= severe agents (Mepolizumab all pathway of biological treatments. inflammatory 2.9% biological with anti-IL-5 on on treated were were suspected) patients (71%) study. highly or asthmatic the (confirmed in severe COVID19 included with Among asthmatics patients severe 26 rhinosinusitis cardio- of non-infected chronic hypertension, out and Twenty-one rhinitis, arterial infected reflux, (including odds between gastroesophageal comorbidities p=0.002; found obesity, was other 3.8%, bronchiectasis, diseases) of vs polyps, vascular prevalence (15.4% nasal the patients without or in asthma with difference severe dia- No non-infected non-insulin-dependent 4.7). to of for prevalence ratio: compared died higher (NIDDM) significantly (7.7%) patients. a mellitus been two non-hospitalized had have betes the patients, COVID-19, by among (15.3%) hospitalized affected reported patients among asthmatics been Four cough Severe (ICU); have (84.6%), (42.3%). Unit deaths Care malaise smell No Intensive pneumonia. patients), of in interstitial of loss COVID-19 which (100% and of fever (42.3%) symptoms. one were exacerbation headache hospitalized, asthma reported (80.8%), controlling symptoms dyspnea for COVID-19 (80.8%), corticosteroids oral frequent period; of most symptomatic course COVID-19 The short the a during needed asthma them of of worsening four experienced patients infected COVID-19 1. (34.6%) suspect 56.2 Figure Nine highly was in or age presented 26) mean is of and cases out females COVID-19 were (11 of (69.2%) confirmed eighteen had 26); asthmatics out severe (15 1504 of out (1.73%) Twenty-six Categorical variables. compare p-value depending to A used and test. was RESULTS: variable, exact test continuous Fisher Kolmogorov- Mann-Whitney each the or The t-test of with Student USA). compared distribution the were IL, of test, variables normality this Chicago, of the (SPSS, result evaluate software the to on 21.0 used SPSS was using test Smirnov performed was analysis Statistical 2003;D.L.n.200 Giugno 24 2007). del Dicembre n.211 ANALYSIS: 21 STATISTICAL (D.L.vo Products del laws Medical MD Italian Governing 2007; the Rules Novembre to The 6 according Tripartite EEC, del Harmonized and 91/507. Community) (ICH Directive Practice European 1996; Clinical the Practice Good in Clinical the of Good procedures for and Guidelines principles the per- to according was formed protocol The (https://effectivehealthcare.ahrq.gov/topics/registries-guide-3rd-edition/research/). 8-10 w fte2 eeeatmtc ihCVD1 ido ASCV2ifcin iharate a with infection; SARS-CoV-2 of died COVID-19 with asthmatics severe 26 the of Two . 14 . 5 < .5wscniee ttsial significant. statistically considered was 0.05 ± 0yas h egahcldistribution geographical The years. 10 4 hsi nln with line in is This . 1 .Altogether All ). Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. auh P eodP ako D otoeyM,EemnJ,Ro L res ,NlnJD, expression Nolin Burchard gene J, related E, Rodriguez-Santana 2020.04.09.034454 SARS-CoV-2 Nickerson S, Pruesse bioRxiv regulate Oh S, strongly epithelium. CL, R, Huntsman inflammation airway Kumar interferon EM, Rios the KM, Wohlford and Rice in JL, 2 V, HM, Type Medina Everman Kang MA. G, S, Seibold MT, Abecasis Salazar EG, MC, Montgomery C, Zody Eng ND, S, A, ACY, Germer Jackson Pastore DA, Mak P, G, ME, Wechsler DeFord Gnesini responses EG, SP, LA, immune Plender asthma 10.1111/all.12627. innate Stanciu Sajuthi doi: impair and MR, - 2015;70(8):910-20. cytokines doi: Edwards Allergy. asthma Th2 7 B, cells. A. in 2020. epithelial Marku Papi respiratory infections G, D, Med. in Caramori Poletti respiratory rhinovirus SL, A, J to viral Johnston Padovani P, K, of Clin Morelli Ito A, Role Spanevello Cleve M, JE. Contoli COVID-19. Gern - 6 Jr, of 4;376(9743):826-34 RF severity Sep Lemanske 2010 of Lancet. WW, exacerbations. Busse risk - increases 5 Relation Asthma in E. Dying Patients Pennington of 10.3949/ccjm.87a.ccc002. Characteristics - and 10.1001/jama.2020.4683. Rate doi: 4 Case-Fatality 2020. S. JAMA. Brusaferro Italy. in in G, Facility 10.1056/NEJMoa2005412 COVID-19 Rezza Care doi: to G, Long-Term 27. SC, a Onder Mar Reddy in - 2020 ND, Covid-19 3 Med. Stone of P, J JR, Epidemiology Montgomery Engl Jacobs B, JS. LP, N Duchin Hiatt V, Washington. Oakley TA, Kawakami D, County, AC, Clark A, Russell King Bardossy Baer MA, FX, MJ, J, Honein Riedo Hughes Lewis JA, MR, F, NG, Jernigan Sayre Tobolowsky Schwartz EJ, TD, M, Chow Rea Kay AK, C, S, Rao Brostrom-Smith Pogosjans S, J, Ferro Clark MD, DW, Lukoff Currie TM, McMichael - 2 2020) June Government: 18th Italian COVID-19. the the of developing Department of Protection Civil risk ex- – low 1 minority at small are our asthmatics a confirm severe to only that needed including REFERENCES patients evidence are features the studies asthmatic clinical extend registry-based severe peculiar real-life to Further had of and comorbidity. patients findings as cohort these NIDDM large and of prevalence a COVID-19, therapy high anti-viral with in to consistent that response symptoms reported better perienced with we associated conclusion, been reported In has been has eosinophils eosinopenia in worldwide reduction: increase patients eosinophils and response that COVID-19 blood COVID-19, immune speculate of antiviral of to consequence tempting on 52-90% the is impact it in of different conclusion, speculate and any may draw specific of we to anti- have addition small proportion with can too treated the treatments patients is COVID-19, of cases biological number of with different the number to asthmatics the compared Although severe (71%) (29%). higher of IgE was agents case-series biologic our anti-IL5 treated of those patients the among Noteworthy, ICS bronchodilators of with doses combined high production or development with infection. cytokine alone the treated related ICS mitigate are the that or asthma and prevent shown might replication have ICS coronavirus studies that asthma. inhibit in-vitro possibility severe the infections: with to Coronaviruses patients refers of of explanation population possible remaining third highly the The found to compared been have asthmatics virus entry) severe COVID-19 cell the NIDDM in SARS-CoV-2 concomitant by with mediating used asthmatics protein molecule in (another airwaysexpressed adhesion (TMPRSS2) allergic the 2 in (ACE2) overexpressed (ICAM1), Protease is Serine 2 1 cells, Molecule enzyme respiratory Adhesion enter angiotensin-converting to Intercellular in where controlled reduction and allergies, allergies significant and respiratory with that reported associated recently expression are been has exposures It asthmatics. allergen severe of proportion great 15 h ellrrcpo o SARS-CoV-2 for receptor cellular the , 11 23 n hsmyhv a rtcieeetfrSARS-CoV-2 for effect protective a had have may this and n thsbe ugse sars atrfrmr severe more for factor risk a as suggested been has it and 19 16 h nycmriiyta a oefeun reported frequent more was that comorbidity only the , h poierltosi cusbtenRhinovirus between occurs relationship opposite The . 6 http://opendatadpc.maps.arcgis.com/apps/opsdashboard/index.html#/b0c68bce2cce478eaac82fe38d4138b1 17,18 neetnl,AE n Transmembrane and ACE2 Interestingly, . 20 ydfiiin ainswt severe with patients definition, By . 21,22 24 In . . (Accessed Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 1-Gl A i H aarn ,Kos Z hoB cit ,Gr E oisA us W Enhanced WW. Busse A, 2018;141(5):1735- Togias Immunol. JE, Clin Gern Allergy A, J Schiltz 10.1016/j.jaci.2017.07.035. B, omalizumab. doi: Shao after RZ, 1743.e9. responses Krouse antiviral A, cell Calatroni H, dendritic coronavirus AH, plasmacytoid Momma Liu epithelial on MA, tracheal Y, Gill budesonide and - Shimotai nasal 21 and K, 10.1016/j.resinv.2019.12.005. human doi: formoterol, of Nomura cultures 2020;58(3):155-168. glycopyrronium, O, Investig. primary Watanabe by of Respir production M, cells. effects cytokine Sugawara and Inhibitory X, replication T. HCoV-229E Deng Kawase H, M, Nishimura Ichinose M, doi: Yamaya 2020. Med. 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COVID-19 15 Stempel GW; the MA, Canonica during Barrett COPD 10.1016/j.jaip.2020.04.053. G, R, and doi: Gondalia Senna 2020. asthma I, G, Smeenk Pract. with B, Immunol patients Pelaia Theye Clin among P, L, Allergy Paggiaro Kaye J - F, Perspectives. 14 and Menzella Findings M, Italy: Latorre in SANI. Network F, GW; 2019;7(5):1462-1468. Asthma Canonica Blasi 2017;15:9. Severe M, Allergy. The Mol E, Latorre Clin Network. E, Heffler asthma. Heffler severe - M, monitor to Caminati 13 forward F, way Blasi a P, PL, Italy: in Paggiaro Gibson EH, Network M, M, Asthma Bel Feb;43(2):343-73. Guerriero SANI-Severe 2014 Gaga ED, G, definition, J. Bateman U, Senna on Respir Frey - IM, guidelines Eur ERS/ATS 12 R, Adcock Distinct International asthma. Djukanovic WG. PJ, severe YD. Teague SE, Sterk of RL, Gao treatment Dahlen Sorkness M, T, and P, CA, Castro Mauad evaluation Chanez A, Akdis NN, C, Bush Jajour YQ, Q, Brightling JL, Yan Hamid LP, Brozek J, Boulet SE, ER, Wenzel Lin Bleecker KF, MY, Chung Liao - BC, 11 Wang 10.1111/all.14316 Clin SARS- X, doi: for J results 2020. rRT-PCR-negative Dong literature. Allergy. and rRT-PCR-positive current YY, CoV-2. initial of with Cao patients review COVID-19 Z, JJ, of A characteristics Zhang Zhang COVID-19: J, Yue of - C, features inpatients 10 Zhang 10.1016/j.jcv.2020.104357. COVID-19 clinical Z, doi: adult and Yang 10;127:104357. in Epidemiology B, Apr mortality Wu Jr. 2020 and 10.1016/j.jaci.2020.04.006. M, severity Virol. JA doi: Zhou for S0091-6749(20)30495-4. Siordia J, factors pii: - Shi 12. Risk Apr 9 Y, J. 2020 Zhou Zhao Immunol. Y, M, Clin Tao Xie Allergy K, J J, Wuhan. Wang Xie in M, X, Yu Liu S, H, Xu Renz X, Li - 8 7 Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. Emilia Emilia 3 Emilia 2 Region 1 ID trimethoprim/sulfamethoxazole; ;TMP-SMX: paracetamol; OCS: ventilation; PCM: me- tocilizumab invasive MV: TOZ: omalizumab; non OMA: mepolizumab; NIV: MEPO: mellitus; corticosteroids; diabetes disorder; oral leukotriene non-insulin-dependent depressive LTRA: NIDDM: lopinavir/ritonavir; major ventilation; MDD: LPV/r: chanical long-acting levofloxacin; heparins; LVX: LAMA: weight antagonists; hyperten- molecular beta2-agonists; AZM: receptor car- HTN: low corticosteroids/Long-acting CVD: LMWH: hydroxychloroquine; Inhaled rhinitis; agents; polyps; HCQ: ICS/LABA: muscarinic nasal allergic disease; ibuprofen; with reflux IBP: rhinosinusitis AR: CRSsNP: gastroesophageal sion; chronic ciprofloxacin; GERD: CRSwNP: amoxicillin/clavulanate; CIP: diseases; polyps; ceftriaxone; AMC: diovascular nasal Cax: without albuterol; bronchiectasis; rhinosinusits BX: chronic ALB: benralizumab; COVID-19. BENRA: with dermatitis; azithromycin; asthmatics severe atopic of characteristics AD: clinical and Demographic – I Table from benefit may 10.1016/j.ijid.2020.03.013. COVID-19 of doi: COVID-19 Patients and of J. 2020;95:183-191. TABLES: outcome Zhang diseases the Dis. W, Yu predict Infect respiratory K, may J Pan Eosinophil Int T, of inflammatory Yan increase progression. W, the chronic Xuan and Y, regimen Zhang COVID-19, Lopinavir-combined doi:10.1111/all.14353 A, sustained Xu Z. 2020. F, Allergy Liu Diamant - series. 24 P, case clinical Banovcin Shadow. reported and Observationsfrom M, Light – Asthma. eosinophils Jesenak in 10.1164/rccm.201809-1684ED. Exacerbation - doi: Virus-induced 2019;199(4):410-411. 23 on Med. Anti-IL-5 Care of Crit Effects Respir A. J Papi Am M, Contoli - 22 Romagna Romagna Romagna ofimd8F3 e oGR ee oICS/LABA, BX, Fever, No NIDDM No Fever No GERD Yes Yes No 33 Comorbidities Yes 33 Smoker F Atopy 34 M BMI Confirmed65 Sex Confirmed67 F Age Confirmed48 19 COVID- firmed Con- or Suspect 8 Osteoporosis iety, Anx- CVD, toms Symp- 19 COVID- Dyspnoea Cough, Fever, Dyspnoea 19 COVID- ing dur- tion ba- er- ac- ex- Asthma oICS/LABAHCQ, ICS/LABA, No No
apy ther- Asthma OCS OMA LTRA,
COVID- 19 Ther- apy
LVX, OCS, MV
HCQ, OCS
HCQ, AZM course ical clin- 19 COVID- Death Recovered Recovered Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. obriCnre4 0YsE CRSwNP, Ex Yes 20 F LombardiaConfirmed45 5 Emilia Region 4 ID Romagna upc 2M3 e oA Fever, AR No Yes Comorbidities Smoker Atopy 33 BMI M Sex Age 32 Suspect 19 COVID- firmed Con- or Suspect 9 GERD, toms Symp- 19 COVID- Ageusia mia, Anos- Malaise, Cough, Fever, Myalgia gia, Arthral- Headache, rhea, Diar- ing, Wheez- noea, p- Dys- throat, Sore sia, Ageu- mia, Anos- Malaise, Cough, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma oICS/LABA, No ICS/LABA, No
apy ther- Asthma MEPO OCS, LTRA, OMA
COVID- 19 Ther- apy
C Recovered HCQ OCS, PCM course ical clin- 19 COVID- Resolved Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. obriSset5 1YsN EDFever, GERD No Yes GERD, 21 No F No 58 LombardiaSuspect 28 8 F LombardiaConfirmed65 7 CRSwNP, No No 27 F LombardiaConfirmed45 Region 6 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 10 Osteoporosis NIDDM, CVD, GERD toms Symp- 19 COVID- Dyspnoea tis, Rhini- Malaise, Cough, failure ratory Respi- noea, Dysp- Cough, Fever, failure tory pira- Res- pain, Chest ness, tight- Chest noea, p- Dys- sia, Ageu- mia, Anos- Malaise, Cough, Fever, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma e ICS/LABA, Yes ICS/LABA, No ICS/LABA, No
apy ther- Asthma OMA MEPO BENRA LTRA,
COVID- 19 Ther- apy
V Resolved LVX OCS, HCQ, LMWH, LVX, NIV OCS course ical clin- 19 COVID- Death Recovered Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 0Lmadaofimd2M3 e oAR, No Yes 33 M LombardiaConfirmed62 AR, Former 10 Yes 26 M 56 LombardiaSuspect Region 9 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 11 HTN BX, GERD, CRSsNP, BX GERD, toms Symp- 19 COVID- Nausea ure, fail- tory pira- Res- ness, tight- Chest noea, p- Dys- mia, Anos- Malaise, Cough, Fever, Arthralgia ing, Wheez- ness, tight- Chest noea, p- Dys- tis, Rhini- Malaise, Cough, Fever, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma oICS/LABA, No ICS/LABA, Yes
apy ther- Asthma MEPO LTRA, MEPO
COVID- 19 Ther- apy
LPV/r, Non HCQ, spec- AZM, ified OCS, antibiotic TOZ course ical clin- 19 COVID- Resolved Resolved Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 2Lmadaupc 1F2 e oNn Fever, None No Yes 25 F 51 LombardiaSuspect 12 AR, Yes Yes 28 F LombardiaConfirmed66 Region 11 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 12 NIDDM Cataract, coma, Glau- CVD, CRSsNP, toms Symp- 19 COVID- Headache ness, tight- Chest noea, p- Dys- throat, Sore sia, Ageu- mia, Anos- Malaise, Headache sea, Nau- ing, Wheez- pain, Chest ness, tight- Chest noea, p- Dys- tis, tivi- junc- Con- Malaise, Cough, Fever, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma oISLBACResolved ICS/LABAAMC No ICS/LABA, Yes
apy ther- Asthma MEPO LTRA,
COVID- 19 Ther- apy
C Resolved OCS course ical clin- 19 COVID- Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 4Peot upc 6F2 e oAR, No Yes 23 F 66 Suspect Piemonte CRSwNP, 14 No No 19 F 37 LombardiaSuspect Region 13 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 13 GERD SwNP, CR- AD toms Symp- 19 COVID- Headache rhea, Diar- ing, Wheez- noea, p- Dys- throat, Sore mia, Anos- tis, Rhini- Malaise, Cough, Fever, Headache ing, Wheez- noea, p- Dys- throat, Sore sia, Ageu- mia, Anos- tis, Rhini- Malaise, Cough, Fever, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma e ICS/LABA, Yes ICS/LABA, Yes
apy ther- Asthma OMA LTRA, MEPO LTRA,
COVID- 19 Ther- apy
ALB, Resolved LVX PCM, IBP course ical clin- 19 COVID- Resolved Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 7Peot upc 9F2 iN oeFever, None No Si 21 CRSwNP, F No No 59 Suspect Piemonte 26 17 AR, F No 66 Suspect Yes Piemonte 34 16 F 57 Suspect Piemonte Region 15 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 14 Osteoporosis MDD, GERD toms Symp- 19 COVID- Headache ing, Wheez- pain, Chest ness, tight- Chest noea, p- Dys- tis, tivi- junc- Con- sia, Ageu- mia, Anos- Malaise, Cough, Headache noea, p- Dys- tis, Rhini- Malaise, Cough, Fever, Wheezing ness, tight- Chest noea, p- Dys- Malaise, Cough, Fever, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma e ICS/LABA, Yes ICS/LABA, No ICS/LABA, Yes
apy ther- Asthma BENRA LAMA, MEPO LAMA, LTRA
COVID- 19 Ther- apy
AMC, CIP, OCS, CIP, PCM PCM TMP- SMX, OCS course ical clin- 19 COVID- Resolved Resolved Resolved Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 2LgraSset4 7YsYsNn Fever, None Yes Yes AR, 27 Fever, Yes None F Yes No 46 28 Fever, Suspect No Liguria None M 23 22 No 50 Suspect Yes F Liguria 23 Confirmed53 21 Veneto Fever, CRSwNP F 20 No 55 Suspect No Piemonte 25 19 M 61 Suspect Piemonte Region 18 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 15 CRSwNP toms Symp- 19 COVID- Diarrhea noea, p- Dys- throat, Sore tis, Rhini- Malaise, Cough, Dyspnoea tis, Rhini- Malaise, Cough, Fever, Anosmia Malaise, Cough, Diarrhea sia, Ageu- Malaise, Cough, Headache rhea, Diar- noea, p- Dys- sia, Ageu- Malaise, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma oICS/LABA, No ICS/LABA, No ICS/LABA, Yes ICS/LABA, No oICS/LABA, No
apy ther- Asthma MEPO MEPO LTRA, OMA LAMA, MEPO LAMA, MEPO
COVID- 19 Ther- apy Z Resolved AZM Resolved None Resolved LVX Resolved None
C Resolved PCM course ical clin- 19 COVID- Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 5CmaiCnre7 9YsE AR, Ex CRSwNP, Yes No 39 No F CRSwNP, 20 CampaniaConfirmed70 Ex F 25 No 60 Suspect Liguria 25 24 M 70 Suspect Liguria Region 23 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 16 NIDDM CVD, GERD, BX Osteopororis toms Symp- 19 COVID- Headache ure, fail- tory pira- Res- ing, Wheez- ness, tight- Chest noea, p- Dys- Malaise, Cough, Fever, Headache noea, p- Dys- Malaise, Cough, Fever, tightness Chest noea, p- Dys- Malaise, Cough, Fever, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma e ICS/LABA, Yes ICS/LABA, No ICS/LABA, No
apy ther- Asthma MEPO LTRA, MEPO OMA
COVID- 19 Ther- apy
AZM, Resolved AZM Resolved OCS Cax, OCS course ical clin- 19 COVID- Resolved Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. ouain h oa ubro ainswt eeeatm o ahsnl eini eotdudrthe under reported is region general single the each the within for within Fever, cases asthma SARS-CoV-2 CRSwNP severe of for with (number positive patients COVID-19 swab name of region nasopharyngeal with number each total positive asthmatics The with severe subjects of population. No and distribution circles) Geographical red – 1 Figure No LEGENDS: FIGURE 28 M Confirmed51 Marche Region 26 ID 9AeSxBIAoySoe Comorbidities Smoker Atopy BMI Sex Age 19 COVID- firmed Con- or Suspect 17 toms Symp- 19 COVID- Myalgia gia, Arthral- Headache, mia, Anos- tis, Rhini- Malaise, 19 COVID- ing dur- tion ba- er- ac- ex- Asthma oICS/LABA, No
apy ther- Asthma MEPO
COVID- 19 Ther- apy
AMC, LMWH course ical clin- 19 COVID- Resolved Posted on Authorea 24 Jun 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159301715.55885907 — This a preprint and has not been peer reviewed. Data may be preliminary. 18