key: cord-293547-29i3u83s
authors: Pfaar, O; Klimek, L; Jutel, M; Akdis, CA; Bousquet, J; Breiteneder, H; Chinthrajah, S; Diamant, Z; Eiwegger, T; Fokkens, WJ; Fritsch, HW; Nadeau, KC; O’Hehir, RE; O’Mahony, L; Rief, W; Sampath, V; Schedlowski, M; Torres, M; Traidl‐Hoffmann, C; Wang, DY; Zhang, L; Bonini, M; Brehler, R; Brough, HA; Chivato, T; Del Giacco, S; Dramburg, S; Gawlik, R; Gelincik, A; Hoffmann‐Sommergruber, K; Hox, V; Knol, E; Lauerma, A; Matricardi, PM; Mortz, CG; Ollert, M; Palomares, O; Riggioni, C; Schwarze, J; Skypala, I; Untersmayr, S; Walusiak‐Skorupa, J; Ansotegui, I; Bachert, C; Bedbrook, A; Bosnic‐Anticevich, S; Brussino, L; Canonica, GW; Cardona, V; Carreiro‐Martins, P; Cruz, AA; Czarlewski, W; Fonseca, JA; Gotua, M; Haatela, T; Ivancevich, JC; Kuna, P; Kvedariene, V; Larenas‐Linnemann, D; Latiff, A; Morais‐Almeida, M; Mullol, J; Naclerio, R; Ohta, K; Okamoto, Y; Onorato, GL; Papadopoulos, NG; Patella, V; Regateiro, FS; Samolinski, B; Suppli Ulrik, C; Toppila‐Salmi, S; Valiulis, A; Ventura, MT; Yorgancioglu, A; Zuberbier, T; Agache, I
title: COVID‐19 pandemic: Practical considerations on the organization of an allergy clinic – an EAACI/ARIA Position Paper
date: 2020-06-12
journal: Allergy
DOI: 10.1111/all.14453
sha: 
doc_id: 293547
cord_uid: 29i3u83s

BACKGROUND: The Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. METHOD: The scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet. RESULTS: Based on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. CONCLUSIONS: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.

On March 11, 2020 , the World Health Organization (WHO) declared the "corona virus disease 2019 (COVID-19)" as a pandemic viral disease. Since the first transmission dynamics reported in China [1] , the number of infected patients and fatalities have been increasing worldwide [2] . Typical symptoms of COVID-19 include general malaise, fever, respiratory problems, and especially cough and shortness of breath. The clinical pattern differentiates somewhat from other airway diseases (Table 1).   INSERT: TABLE 1   Table 1 : Differences and similarities in the clinical pattern of COVID-19, common cold, flu, allergic rhinitis, chronic rhinosinusitis and allergic asthma (modified from [3] ).

Other symptoms include muscle and joint pain, sore throat, headache, nausea or vomiting, diarrhoea, nasal symptoms, and especially dysfunction in smell and loss of taste. In about 80% of the registered cases, the disease shows a milder and transient course. However, in about 5% of patients, admission to the intensive care unit (ICU) is necessary due to hypoxaemia and extensive pneumonia, often resulting in respiratory failure due to severe acute respiratory syndrome, often accompanied by coagulopathy and pulmonary embolism and the involvement of other organs including kidney, heart, and the central nervous system [4] [5] [2] . Preventive measures have been implemented worldwide to adjust ambulatory health services and decrease direct patient contacts to a minimum. However, until now, there is no clear advice on how to manage allergic patients with co-morbid COVID-19 or non-SARS-CoV-2 infected allergic patients during the ongoing pandemic [6] . The European Academy of Allergy and Clinical Immunology (EAACI) in alliance with the global initiative "Allergic Rhinitis and Its Impact on Asthma" (ARIA) has published several recommendations and assessments in the field of allergic diseases such as allergic rhinoconjunctivitis (ARC), allergic

This article is protected by copyright. All rights reserved asthma and others [7] regarding pharmacotherapy, Allergen Immunotherapy (AIT), biological treatment and others [5] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] .

As allergists and other healthcare providers (HCPs) with a focus on allergic diseases are frequently treating patients with manifestations of atopic disease in the upper and lower airways, they are on the front line in caring for patients potentially infected with SARS-CoV-2. As such, the clinical setting in an allergy outpatient clinic or hospital must ensure optimal care for the patients as well as sufficient prophylactic measures to minimize risks of infection for both the medical personnel and the patients requiring treatment as reported in an academic Allergy Centre initiative [19] . Therefore, clinical procedures in allergy clinics and outpatient practices must be optimized and standardized, within the contextual considerations regarding national regulations [20] .

The aim of this Position Paper -prepared by EAACI in collaboration with ARIAis to provide allergy clinics, specialized centres and practices with practical recommendations on measures for daily practice and optimal care for allergic patients 

This article is protected by copyright. All rights reserved 

This article is protected by copyright. All rights reserved Coronaviruses, just like the common cold viruses, may be associated with aggravation of asthma exacerbations [27] by stimulation of type 2 immune response associated cytokine production in infected epithelial cells [28] . Allergic diseases might predispose

This article is protected by copyright. All rights reserved to viral infections or a deferred viral clearance due to delayed and deficient production of the innate type I and type III interferons and/or deficient epithelial barrier function [29] [30] .

Until now, limited knowledge has been available on the differences in the course of [36] . The technique of documenting allergological history in telemedicine follows generally accepted principles of medical conversation.

Standardized and validated questionnaires for quantifying symptoms can complement the analysis of the history, be prefilled by the patient before telemedicine consultation, document the collected data and facilitate computer-assisted evaluation [37] . Patients with a clear need for in-person consultation in the allergy clinic ( Figure   1 ) should be identified, triaged to the clinic and instructed on the procedures to be followed in the clinic.

This article is protected by copyright. All rights reserved INSERT: Figure 1 here For milder forms, patients should be offered alternative solutions whenever possible to avoid any unnecessary risks associated with a real-life consultation, e.g., shipping electronic inhalation monitoring devices, peak-flow meters, and providing prescription for medication (see section "clinical setting"). In particular, allergic patients with mild symptoms regularly attending the outpatient clinic should be instructed to continue their medication including inhaled corticosteroids (ICS) and intranasal corticosteroids (INCS), AIT and biologicals targeting the T2 immune response as prescribed. Whenever possible, on-site administration in clinics for sublingual AIT and biologicals should be replaced by (self) administration at home with close monitoring, and sufficient supplies of medication should be provided. Local community organisations and health services could be engaged to assist patients who are treated at home and who may need support services in order to ensure optimal care. In some cases, trained clinic nurses can assist by telephone. Additionally, these patients should be well instructed regarding proper prevention measures for allergen exposure control, e.g. using peakflow measurements or Apps [38] [39] [40] , and food avoidance [41] (especially with online ordering and shipping where no individual selection of food is feasible). They should also be motivated to notify their HCPs in the case of exacerbation or deterioration of symptoms which cannot be appropriately managed at home.

Conclusions: Many clinics and medical offices already use these remote health care tools to triage and manage patients after hours and as part of usual practices. These

This article is protected by copyright. All rights reserved measures can ideally be used to prioritize and triage allergic patients on the basis of the severity of the allergic disease, the need for in-person consultation and the differentiation of allergic symptoms from clinical symptoms of COVID-19.

Combining the need for regular consultations and the highest degree of protection for both patients with allergic conditions and healthcare workers is a significant challenge in the current pandemic. Digital health solutions, especially the use of telemedicine, have been previously proposed as a useful tool to provide medical advice remotely when physical presence is impossible [42] [36] [43] [44] . These technologies are now significantly gaining momentum [45] . However, certain limitations need to be considered.

As such, Electronic Health Records (EHRs) have now been adopted by most major healthcare organizations. They facilitate remote access and offer greater flexibility than paper-based medical records, a factor that is particularly important during the major clinic restructuring that is occurring during the current COVID-19 pandemic.

Here we discuss some of the online tools and apps that can aid researchers, clinicians and other healthcare staff in working with each other (team communications) and with patients (clinical encounters) while working at different locations.

Every internet connection to other communication partners also involves a certain risk.

Normally, clinical and company IT networks are secured from external networks -e.g.

the internet -by a complex security infrastructure such as firewalls, separate security zones (DMZ = demilitarized zones), web content filters, intrusion detection systems and virus scanners. These systems protect internal clinical networks and also protect from hacker attacks and insecure processes from the internet. Data protection and legal regulations

The use of messenger and / or video services in the healthcare sector is particularly worrying from a data protection perspective. It is a classic area handling particularly "sensitive" and protected data. The processing of healthcare data is even prohibited In this context it should be noted that:

-When using videoconferencing apps, the terms and conditions and privacy policies of the providers must be observed.

-Usage should be conducted in compliance with institution-specific policies and country-specific laws -Most of these apps prohibit commercial use of the service without a separate agreement. This may call into question the lawful use of these apps for healthcare communications.

-If the user agrees to the Legal Infos of the apps, he/she often grants the manufacturers of the apps the rights of use of the transferred data, images etc.. 

This article is protected by copyright. All rights reserved cell phone apps that can be used to communicate with smaller groups. In addition to individually owned cell phones, additional cell phones can be shared by members of nursing and administration staff. Office phones can be forwarded to these 'hot'

phones. Call forwarding between cell phones should be utilized based on a roster for receiving incoming calls.

Many of these tools allow the generation of distinct channels to capture relevant discussions and to ensure patient follow-up. These can include clinic-specific channels to capture logistics of billing, scheduling, rebooking and deferring patients, as well as patient-specific channels to capture follow-up required by nurses and doctors. For all channels, the ability to 'tag' staff and reply to comments can be utilized.

Virtual Furthermore, it is important to have a direct "peer to peer" connection between the doctor's video workplace and the patient's workplace in order to prevent unauthorised third parties from recording the video stream. Corresponding security aspects must be taken into account (see also "cybersecurity").

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Conclusions: Digital health solutions, especially the use of telemedicine, has been previously proposed as a useful tool to provide medical advice remotely when physical presence is impossible or should be limited to a strict minimum such as in the current COVID-19 pandemic. However, certain limitations of this technology need to be considered and special emphasis should be placed on data-security and -protection.

Public transport to and from a COVID-19 hospital Transportation to and from the hospital should follow common healthcare recommendations. Public transport should have clear signs that it is going to the COVID-19 specialty hospital. At the last stop, the bus should be thoroughly disinfected.

The driver's seat should be protected by a transparent plastic wall and the patients should be at least 2 metres away [56] . 

This article is protected by copyright. All rights reserved admission and placed in isolation until the results are ready [57] 

In order to reduce the risk of the healthcare workers becoming infected, which would result in service disruption, new forms of staff deployment need to be elaborated. The personnel in the triage area should wear a FFP2/3 mask as well as a face shield, goggles, gown, gloves, and closed shoes.

A two-team approach has been adopted in many large hospital-based departments with no or minimal contact between the two teams. A popular method involves:

1. "Team One": Inpatient COVID-19 deployment including Consultant, Senior

Registrar, Junior Medical Officer. Several such groups could form a roster depending on unit and hospital size.

2. "Team Two": Outpatient allergy/asthma/immunology predominantly operating a virtual call centre approach and ideally remotely operating in staff homes.

A designated deputy head of department and subleads for Allergy/Asthma/Immunology provide a backup framework for key personnel in the case of staff infection requiring substantial self-isolation and resulting in workforce disruption. In COVID-19 patientoverloaded clinics, day and night shifts can be decreased to 6 hours in order to avoid extreme fatigue and thus reduce the risk of HCP errors and infection. Moreover, there is an urgent need for staff training resources and mechanisms to ensure a constant retraining of the most important policies. This regular training has to involve all of the staff members.

This article is protected by copyright. All rights reserved Any service that does not require a diagnostic or onsite therapeutic procedure should be undertaken via telemedicine consultation [58] .

For regular non acute care: only patients requiring a timely diagnostic or therapeutic procedure should be seen in the hospital. A history of identifying potential infected contacts, recent travel and early symptoms such as anosmia and dysgeusia [59] [60]

should be obtained from all patients before any in-person consultation in the clinical setting [61] . There is now ample evidence that COVID-19 may be contagious before the onset of the classical symptoms of cough and high fever [8] . Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority.

Recently, a probable association between COVID-19 and altered olfactory and gustatory function has been reported by several groups, often as the presenting symptom [60] [62]. To evaluate whether this could be a first symptom of COVID-19 can be particularly challenging when treating allergic and rhinosinusitis patients.

Establishing COVID-19 free zones in the hospital includes a strict screening protocol to ensure that patients who are entering the clinic are not infected by COVID-19.

symptoms, fever, but also anosmia, and/or recent contact with a COVID-19 positive subject) should not be admitted to these areas [63] . These patients should be guided to the COVID-19 clinic for further screening evaluation.

To decrease the density of patients, the waiting area should be separate from the treatment area, the number of appointments reduced, and appointments should be scheduled with ample time intervals and online consulting services whenever possible [64] .

Precise appointment times are particularly important during the COVID-19 pandemic as this can greatly reduce patient-patient and patient-HCP hospital-acquired crossinfections. Also, precise appointments can ensure that patients stay in the hospital for a minimum amount of time and that the medical staff are fully prepared with personal protective equipment. Moreover, the patient should be admitted to a consulting room with good ventilation and, at the same time, there should not be more than one patient in the waiting area for visiting or post-immunotherapy observation.

This article is protected by copyright. All rights reserved For further details, see nasal endoscopy during COVID-19 [24] .

Conclusions: General hygiene rules should be followed, especially in the preclinical and clinical setting. The entrance, which is the first point of contact, further patient traffic organization as well as the triage of allergic patients should be organized to minimize the risks of viral infection. Moreover, the organization of staff should be optimized and regular training of procedures should be provided. Any physical contact with the patient should be minimized, and effective preventive measures should be carried out for any further examination and diagnostic.

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The following sections overview the specific considerations for diagnostic procedures in different allergic diseases in a clinical setting during the current pandemic. The indication and the urgency for these tests should be taken into account and can be confirmed, for example by an initial visit performed via telemedicine.

Contraindications for skin tests, provocation tests and lung function tests can be clarified, and this can help to avoid unnecessary in-person consultation with patients during the COVID-19 pandemic.

ENT examination, nasal provocation testing and sampling procedures SARS-CoV-2 spreads primarily through respiratory aerosols, and higher viral loads have been detected in nasal swabs compared to other locations [65] . Thus, rhinoscopy, nasal endoscopy, nasal provocation testing, smell-and taste testing and samplings are highrisk procedures. Nasal provocation tests should be avoided, whereas rhinoscopy, endoscopy and nasal samplings should be limited to patients with an urgent need for examination [64] . A tower with camera, screen and light source can maximize the examiner-patient distance during endoscopy [24] . The use of anaesthetic spray can be replaced by a soaked pledget, thus avoiding virus atomization [24] . The examiner should wear the adequate personal protective equipment recommended for HCPs: FFP2 or FFP3 face mask, goggles or disposable face shield covering the front and sides of the face, clean gloves, and clean isolation gown [66] . 

This article is protected by copyright. All rights reserved Skin testing and blood-sample collection for diagnostic use Skin testing should be generally suspended during the current pandemic. Nevertheless, exceptions can be considered after a careful/proper risk-benefit assessment or may be replaced by laboratory tests. When collecting biological samples or conducting skin testing, the personnel must use the recommended personal protective equipment [66] and also follow the standard precautions (SP) when handling clinical specimens, all of which may contain potentially infectious materials [71] . In this case, a laboratory gown and a single-use waterproof apron may replace the isolation gown [ Therefore, these procedures should be performed inside a biological safety cabinet and using centrifuge safety cups and sealed rotors [71] . Work surfaces and equipment should be appropriately decontaminated and laboratory waste should be handled as biohazardous agents [75] . The inactivation of serum samples suspected to be contaminated with SARS-CoV-2 should be carried out by following the procedure recommended by WHO for serum samples for ELISA-based analysis [76] . 

Cough, sneezing or rhinorrea may occur during drug provocation tests [78] [79] .

Therefore, these procedures should not be generally conducted during the current pandemic [79] . Nevertheless, exceptions can be considered after a proper risk-benefit

This article is protected by copyright. All rights reserved assessment. Examples of these include chemotherapy in oncologic patients, perioperative drugs or radiocontrast media in subjects needing urgent procedures, or antibiotics in infected individuals without any alternative effective drug [80] [81] .

Oral food challenges and esophageal examination

Oral food challenge may induce respiratory symptoms with aerosol-generating potential, together with vomiting and diarrhoea [82] . Importantly, the virus can persist in gastrointestinal fluids for a longer period than in the respiratory specimens [83] .

Therefore, oral food challenges should be avoided during the current pandemic, as they lack urgency [84] . The diagnosis of eosinophilic esophagitis requires a gastroscopyguided esophageal biopsy [85] . The performance of a gastroscopy is not recommended during the current pandemic, due to the possible persistence of virus in biological fluids [86] . In the case of extreme need (e.g. frequent food impaction), a proper riskbenefit assessment should be conducted [87] . 

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This article is protected by copyright. All rights reserved Strict avoidance measures must be taken and an adrenalin auto-injector must be carried.

-Continue SCIT.

This article is protected by copyright. All rights reserved Atopic dermatitis is one of the most common skin disorders. The lifetime prevalence varies between 0.2% and 25% worldwide, the most effected area being the northern part of Europe [90] . The disease most often starts in early childhood and persists into adult life in up to 50% of affected patients [91] . Co-morbidities with other atopic diseases including asthma, allergic rhinitis and food allergy are common [92] . Most with mild to moderate atopic dermatitis can be controlled on topical treatment. However, in the severe cases, systemic immune-modulating treatments including immunosuppressive therapy is needed [93] . Conventional systemic immuno-suppressive treatment, such as Ciclosporin, may interact with the human body's defense

This article is protected by copyright. All rights reserved mechanisms against viral disease, while Dupilumab, which is registered in many countries for the treatment of moderate to severe atopic dermatitis, selectively interferes with type 2 inflammation and is in general not considered to increase the risk for viral infections.

It is well known that viral and bacterial infection may complicate and exacerbate atopic dermatitis including infections with Staphylococcus aureus (impetigo), poxvirus (molluscum contagiosum) and Herpes Simplex virus (eczema herpeticum) [92] . Severe and untreated atopic dermatitis is a known risk factor for disseminated viral skin disease [94] .

In the current SARS-CoV-2 pandemic, the European Task Force on Atopic Dermatitis (ETFAD) recommends to continue all immune-modulating treatment since exacerbations of underlying diseases can have a large negative impact on the patient's immunity [30] . However, patients at risk are advised to strictly follow the recommendations issued by the local health authorities in each European country [30] .

The British Association of Dermatologists (BAD) has addressed potential issues regarding the COVID-19 infection of patients undergoing immune-modulating treatment [95] .

Other countries will follow. A thorough hygienic procedure is recommended with hand washing and disinfectants. Non-irritant soap substitutes should be used following the same instructions as those for regular soap. Moisturizers should be applied afterwards.

In the case of COVID-19-infected atopic dermatitis patients, interdisciplinary risk assessment should be carried out and, in accordance with current guidelines on active infections and systemic therapy, the immune-modulating therapy may or may not be paused afterwards [30] . If systemic treatment is paused, it is important to optimize the topical treatment. Furthermore, if the paused systemic treatment also has an effect on co-morbidity such as asthma, then the co-morbidity also has to be treated by other drugs. According to a letter from Italy regarding 245 patients on therapy with Dupilumab, only two developed COVID-19 [96] . An abnormal course of COVID-19 was not observed in these 2 patients. More clinical data are needed for this specific treatment.

This article is protected by copyright. All rights reserved Urticaria is characterized by the development of wheals (hives), angioedema or both [97] . Acute urticaria is defined as the occurrence of wheals, angioedema or both for less than 6 weeks. Chronic urticaria is defined as wheals, angioedema or both for 6 weeks or more [97] . Viral infection has been found as a potential trigger -and sometimes as the main etiologic agent -in causing acute or chronic urticaria [98] .

In Italy, 88 patients with COVID-19 were studied by a group of dermatologists. 20% developed cutaneous symptoms including erythematous rash and urticaria. It was concluded that the skin manifestations related to the COVID-19 infection are similar to those occurring during common viral infections [99] . In France, among 103 out-and inpatients with confirmed COVID-19 infection, two had urticaria [100] . In a study from China, 1.4% of the COVID-19 patients reported an underlying urticaria. However, skin symptoms during the infection were not described [5] . The manifestation of urticaria could appear before the onset of fever or respiratory symptoms [101] .

As a consequence of these observations, the manifestation of acute urticaria could be an indication to test for SARS-CoV-2. According to the guidelines, second-generation H1-antihistamines are the base of urticaria treatment [97] and should be continued during the pandemic. If urticaria cannot be controlled on antihistamines in four-fold dose, Omalizumab is recommended as an add-on treatment. Omalizumab is registered for self-administration after patients have received training on the injection technique and on the assessment of allergic side effects. Only the first two injections need to be administered in hospital, due to the risk of anaphylaxis. Therefore, especially during the COVID pandemic, treatment at home is favourable. By telemedical visits, the efficacy of the treatment can be evaluated and patients' questions regarding the treatment may be reviewed. This is currently recommended by the BAD [95] . As for all COVID-19 infected patients, interdisciplinary risk assessment should be performed and,

in accordance with current guidelines on active infections and systemic therapy, the immune-modulating therapy may or may not be paused afterwards.

Many reactions to foods are mild-moderate and can be self managed by the patient,

given the availability of an up-to-date action plan and adequate rescue medication.

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During periods of isolation, it is vital that children and adults with food allergy have access to suitable foods according to their dietary recommendations [102] . Patients with a history of severe anaphylactic reaction urgently need an emergency health card providing information on the diagnosis, eliciting (causative) allergens, and necessary treatment in the case of a severe reaction and / or an unexpected hospital admission due to COVID-19 [103] . Oral (OIT) and epicutaneous immunotherapy (EPIT) for Food

Allergy should follow the general rules of EAACI/ARIA for AIT during COVID-19 pandemic (description in subchapter "allergic rhinoconjunctivitis").

In the case of an anaphylactic reaction due to an actual insect sting, patients should be treated according to the guidelines. Especially in high-risk patients (e.g. high risk for subsequent stings, patient suffering from mastocytosis, patient with grade 3 or 4 anaphylaxis), the diagnosis of insect venom allergy must be proved urgently. Venom immunotherapy should be initiated without any delay in order to prevent severe reactions in the case of further stings in the future [104] . The treatment should follow the general rules of EAACI/ARIA for AIT during COVID-19 pandemic (description in subchapter "allergic rhinoconjunctivitis"). Patients must be informed regarding avoidance strategies and provided with drugs for self-administration. Adrenaline autoinjectors must be prescribed, and patients must be trained to use these devices.

Prior to the initiation of venom immunotherapy, contraindications and requirements for treatment can be discussed with the patient in a telemedicine consultation.

Severe allergic reactions to drugs must be treated immediately. Diagnostic testing may be urgently indicated in the case of a suspicion of allergic reaction to highly necessary drugs. This may be the case for example in patients suffering from reactions to antibiotics which may be necessary to treat bacterial superinfection in COVID-19

pneumonia. In the case of an immediate need for treatment with a drug that is suspected to be responsible for systemic allergic reactions, drug desensitization is a

This article is protected by copyright. All rights reserved therapeutic procedure whose aim is to induce a temporary state of unresponsiveness to a drug in a patient with confirmed allergy. During drug desensitization, respiratory and gastrointestinal symptoms occur commonly [105] [106] with a subsequent risk of spreading infectious aerosols. Therefore, the decision to conduct the procedure during the current pandemic must consider both the expected benefits obtained from the drug administration, as well as the potential risks of severe reaction and infection spread [89] . Absolute indications for desensitization may include chemotherapeutic agents in oncologic patients, aspirin in subjects with ischemic diseases and antibiotics in infected individuals when no effective alternative is available [107] .

Chronic rhinosinusitis (CRS) affects approximately 5-12% of the general population worldwide and is regarded as a chronic airway disease, that, according to WHO recommendations, may be a risk factor for COVID-19 patients [6] [11] . The inflammatory changes affecting the nasal and paranasal mucous membranes in CRS with nasal polyps (CRSwNP) are, in most cases, of the type 2 (T2) inflammation endotype. They are typically associated with epithelial damage and tissue destruction [108] , which can promote viral infections [109] . Asthma often coexists with CRSwNP and it is known that deterioration in the control of CRSwNP can promote asthma exacerbations [109] .

Symptoms of nasal obstruction, rhinorrhea, facial pressure and smell problems regularly occur in CRS. Recently, a number of reports have been indicating that a sudden and severe (anosmia) isolated onset of loss of smell (ISOA) and/or loss of taste may also be present in COVID-19 patients who are otherwise asymptomatic. This is considered a marker symptom in screening for SARS CoV-2 infection [110] [111] [62] , but may also interfere with loss of smell in CRS [11] . CRS is treated with intranasal corticosteroids (INCS), systemic corticosteroids or specific, T2 endotype-driven antiinflammatory therapies according to the severity of disease [112] . INCS remain the standard treatment for CRS in the COVID-19 pandemic and also for patients with SARS-CoV-2 infection [11] . Surgical treatments should be reduced to a minimum and surgery should be preserved only for patients with local complications and those for whom no

This article is protected by copyright. All rights reserved other treatment options exists. Systemic corticosteroids should be avoided. Treatment of severe uncontrolled CRSwNP patients [112] with biologicals can be continued with careful monitoring in non-infected patients. However, it should be temporarily discontinued in patients having tested positive for SARS-CoV-2 (RT-PCR), until recovery.

We suggest that physicians assess the risks vs. benefits in low-risk patients before initiating biologics therapy on a case-by-case basis. However, it should not be initiated in high-risk patients [11] [9].

There have been reports that topical applied "corticosteroid preparations" may increase the risk of developing COVID-19 or may cause a more severe course of the disease. This opinion massively unsettled numerous patients suffering from allergic rhinitis (AR), CRS or asthma. A current Position Paper by ARIA and EAACI on AR treatment [88] states that Therefore, it is recommended that patients with AR should continue to regularly use their INCS at the individually-prescribed dose. Hence, it is not advised that they change or even stop their treatment without consulting their doctor [88] . Discontinuation of INCS may worsen AR symptoms with increased secretion and sneezing which may promote viral droplet transmission from SARS-Co-2 infected patients to healthy individuals [88] . In addition, worsening of AR can trigger an exacerbation of asthma [88] , which is regarded by WHO as a risk factor for severe courses of COVID-19.

Systemic glucocorticosteroids in general have several adverse effects if given long term [114] . For AR, they should be used with even more caution during the current COVID-19

pandemic and only when no therapeutic alternatives are available [88] because of a potential temporary immunosuppression and a possible increased risk of contracting a SARS-CoV-2 infection or progression to severe disease [114] .

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Allergen immunotherapy (AIT) is the only disease-modifing treatment option for patients with allergic diseases as applied through the subcutaneous (SCIT) or sublingual route (SLIT) [115] [116] . During the current pandemic, special considerations should be introduced to the management of AIT [117] [10] . All in-person consultation may be preceded and prepared by a telemedicine visit, during which information is obtained about the patient´s health status and possible contraindications for AIT. Since SLIT is self-administred at home during the maintenance phase, telemedicine visits may be helpful for advising patients and increasing their adherence to treatment.

In noninfected individuals during the COVID-19 pandemic or in patients having If AIT is stopped due to signs of a potential SARS-CoV-2 infection (such as fever, cough, dyspnea), or due to other signs of ill health, or due to local restrictions on clinic operations, it should be resumed after recovery but with proper dosage adjustment and under medical supervision when appropriate. To maintain social distancing procedures in the clinic, the following methods could be considered: stretching out the interval of IT or organizing different clinic hours to limit the number of patients attending for IT

[10] [118] .

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To date, there is very little information available on patients with asthma who have COVID-19. In general, viruses, including rhinoviruses and respiratory synctial viruses, have been shown to induce asthma episodes or exacerbations [119] [120] . Mounting evidence implicates that particular viral pathogens, namely the human rhinovirus and respiratory syncytial virus, are among the most likely culprits in asthma inception [120] . Bacterial infections and colonization have also been associated with exacerbation and recurrent wheeze, an effect that may be independent, or a cofactor with viruses. In addition, certain individuals may have a genetic predisposition towards viral-induced wheezing and the development of asthma [120] . Whether this also applies to SARS-CoV-2 infection remains to be seen. Interestingly, according to initial reports, allergic airway disease including asthma did not appear to be a risk factor for COVID-19

or for a severe clinical course [5] [8] [121] . However, more recent reports from the USA show asthma as an underlying condition in 13-27% of patients hospitalized with COVID-19, within the COVID-NET hospitals [33] . Additionally, immunocompromised patientsincluding the elderly, those with diabetes mellitus or those on (systemic) corticosteroids in conjunction with the underlying immune disorders -may be at an increased risk of being infected and more severely affected by SARS-CoV-2 [5] [122] .

Optimal disease control is the first defense against respiratory triggers including infections in patients with inflammatory airway disease such as allergic rhinitis and asthma. Inhaled maintenance therapy with bronchodilators and ICS should not be stopped during the COVID-19 pandemic [13] . The termination of inhaled treatment may in fact imply an increased risk for asthma symptom worsening and acute airway exacerbations. Furthermore, the risk of asthma deteriorating in a threatening manner and necessitating (otherwise unscheduled) doctor visits or hospital stays -potentially responsible for contact with COVID-19 patients -is far more dangerous for asthmatic patients than a possible increased risk of SARS-Cov-2 infection due to a theoretic local immunodepression induced by ICS. Given the lack of current evidence that ICS negatively affect the COVID-19 outcome, experts and professional societies within the respiratory and allergy field -including the Global Inititiative on Asthma (GINA), the American Academy of Allergy, Asthma and Immunology (AAAAI), the European

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Respiratory Society (ERS) and EAACI -all stress the importance of disease control, especially since many countries are now entering the spring pollen season [13] . 

This article is protected by copyright. All rights reserved participated in COVID-19 clinical trials and it is important to note which medication was potentially administered (see section "Considerations for performing clinical trials"). When resuming allergy care, clinical judgement should determine whether additional labs (complete blood count, liver function test, kidney function) or lung function testing are necessary before restarting the treatment of allergic diseases and this decision should be based on a multidisciplinary consultation. In some cases, a close follow-up to assess pulmonary rehabilitation may be warranted.

INSERT: Figure 3 here infection.

After recovery from COVID-19, allergy care has to be resumed, but an interdisciplinary consultation is recommended before any further diagnostic or therapeutic procedure.

VIII. Socio-psychological considerations for allergic patients and optimal care during and after the pandemic Allergic responses are affected by psychological factors such as stress and anxiety and can be modulated by interventions other than conventional drug therapy [133] . These psychological mechanisms play a role in terms of symptom development, symptom exacerbation and perception [134, 135] . The reactions of other people to patients

showing allergic respiratory symptoms during the COVID-19 pandemic are amplified.

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These reactions, along with the governmental regulations (e.g., social distancing) for dealing with the pandemic, induce further stigmatization and thus enhance psychosocial stress for allergic patients.

Symptom development and symptom perception are only partially caused by the biological mechanisms of the allergy, and many patients report bodily symptoms that are mainly developed via psychological effects (nocebo effects). Relevant psychological mechanisms for symptom development include: negative expectations, increased selfobservation of somatic reactions, catastrophizing of perceived symptom (dysfunctional appraisal), as well as fears and negative affect [136] . For many patients (and sometimes even for their physician), the reported symptoms are a conglomerate of potential allergic symptoms, potential symptoms of COVID-19, and correlates of concern that are almost impossible to disentangle. These nocebo symptoms can account for up to 80% of patients with medical conditions [137] .

During the COVID-19 pandemic, the general population is highly sensitive to the perception of people showing respiratory symptoms. This increases the risk of stigmatization of patients with allergies, further increasing the psychosocial stress of the patients. The neuroendocrine and immunological consequences of stress exposure are in turn able to amplify the development of allergic symptoms [134] [138] . Negative effects on the willingness to expose oneself to those contacts (e.g. at work, in private social networks) are further potential consequences with negative impact on health conditions. This is even more problematic, because social contact and social support can dampen negative stress effects and reduce disease symptoms [139] . Several recommendations to improve medical care for patients with allergies during the COVID-19 pandemic can be given (Table 5) . 

This article is protected by copyright. All rights reserved  Despite public encouragement for social distancing and increased social stigmatization in the public, patients should be encouraged to maintain an active social network employing the available communication channels. Social support is a crucial factor for improving health in general.

 Encourage patients to do regular physical exercise. Regular physical activities induce antiinflammatory responses.

 An empathetic, reliable and predictable doctor-patient relationship guarantees patient compliance with medical recommendations and lowers nocebo effects.

 Encourage engagement in stress reduction activities such as relaxation techniques, mindfulness, yoga. [36] .

 Provide specific instructions on clinical trial unit procedures, particularly those that generate aerosols/droplets (e.g., sputum and nasal fluid collection, nasal and bronchial provocation testing). All isolations of peripheral blood mononuclear cells (PBMC) and bronchoalveloar lavages (BAL) should be performed in a BSL2 bench. For centrifugation steps, the use of closed beakers should be mandatory.

 Provide specific instructions for the collecting, handling and processing/testing of specimens from clinical trial participants. 

This article is protected by copyright. All rights reserved as well as with all enrolled participants, to inform them of the changes related to the pandemic. All immediate actions should take place as long as the pandemic-related policies are in place and documented. Otherwiese, conventional amendments are required.

Essential non-COVID-19-related research can be continued safely during the COVID-19

pandemic while maintaining data integrity with appropriate amendments to the protocols. These adjustments should take into consideration modern technological communication tools (between hospital staff and patients), IP delivery, appropriate laboratory safety guidelines, and proper source (case report form (CRF)), statistical analysis plan and regulatory documentation (Figure 4 ).

INSERT: Figure 4 here Further guidance for the investigational product should be followed (table 7) .

o Treatment initiation and dose increases only performed in clinic; levels maintained at a stable dosage (e.g. for oral immunotherapy) when clinic visits not possible o Training of at-home administration of biologics and injectables, where applicable [9] Accepted Article This article is protected by copyright. All rights reserved o Ensuring participants maintain adequate IP supply to continue at-home dosing as needed without disclosing identity via research pharmacy (direct-to-participant shipments or curbside dispensing)

o Ensuring integrity between pharmacy and participant in the case of shipping (secure chain of custody and monitoring of storage conditions in transit)

o Necessary rescue medication provision with written instructions and emergency phone numbers 

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In view of the ongoing and emerging novel coronavirus (COVID-19) pandemic spreading worldwide [2] , the safety and well-being of our patients, personnel, and colleagues globally are of primary importance. EAACI and ARIA are closely monitoring the situation. They recommend aligning any diagnostic and treatment operations with guidance from WHO [25] and ECDC [26] , in accordance with all applicable national/regional/local government and public health authority requirements.

Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are on the front line in taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks for infection of both

HCPs and the treated patients have to be developed and followed by allergy clinics [20] . This is especially important in high-risk patients for the course of a SARS-CoV-2 infection e.g. of older age or with comorbidities.

If patients are diagnosed with COVID-19 or are suspected to have COVID-19, they should follow the local area treatment and quarantine guidance. In general, most medications should be continued [88] [10]. Patients may be unable to attend clinic visits, have examinations and/or receive prescriptions. E-Health and telemedicine can assess the value of specialized treatments, provide education for self-management without the risk of infection [44] , and triage patients for urgent in-person consultations. Examples for the latter are diagnostic testing in drug allergy in the case of suspicion of allergic reaction to highly necessary drugs [89] or the application of medication (e.g., SCIT or biologicals) through a HCP.

Clinic staff should keep in contact with the patient preferably through telephone calls or video conferences to maintain awareness of their status in the case of symptom exacerbations. Dispensing a sufficient amount of medication is a way of enabling the patient to self-treat. In treatment with biologicals, the decision to continue or discontinue a treatment should be made on a case-by-case basis by the attending physician, since the safety and efficacy of the mentioned biologicals in COVID-19

patients are currently unknown [9] . Besides, psychological care for patients with allergies during the COVID-19 pandemic is essential.

This article is protected by copyright. All rights reserved Non-COVID trials may be able to be continued according to regional regulations.

However, special emphasis should continue to be placed on the safety of the participants and research/laboratory staff. The same safety precautions used in clinical routine for aerosol-generating procedures and handling of samples should also be applied in the non-COVID trials.

According to WHO and ECDC, patients at risk or with diagnosed COVID-19 should As doctors, scientists and specialist societies, we are required to observe our patients, to provide optimal advice and treatment based on the current state of medical knowledge, and to inform them accordingly when new evidence is available, making it possible to adapt the therapies. EAACI has a prevailing requirement to protect the safety and welfare of our patients, allergists and staff and is working diligently to ensure responses to new recommendations as quickly as possible.

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This article is protected by copyright. All rights reserved Accepted Article