key: cord-0980452-ybzvbygp authors: Pfaar, Oliver; Agache, Ioana; Bonini, Matteo; Brough, Helen Annaruth; Chivato, Tomás; Del Giacco, Stefano R.; Gawlik, Radoslaw; Gelincik, Aslı; Hoffmann‐Sommergruber, Karin; Jutel, Marek; Klimek, Ludger; Knol, Edward F.; Lauerma, Antti; Ollert, Markus; O’Mahony, Liam; Mortz, Charlotte G.; Palomares, Oscar; Riggioni, Carmen; Schwarze, Jürgen; Skypala, Isabel; Torres, María José; Untersmayr, Eva; Walusiak‐Skorupa, Jolanta; Chaker, Adam; Giovannini, Mattia; Heffler, Enrico; Jensen‐Jarolim, Erika; Quecchia, Cristina; Sandoval‐Ruballos, Mónica; Sahiner, Umit; Tomić Spirić, Vesna; Alvaro‐Lozano, Montserrat title: COVID‐19 pandemic and allergen immunotherapy – an EAACI survey date: 2021-03-02 journal: Allergy DOI: 10.1111/all.14793 sha: 1a0c724790e23566e91d1939e75573b9fd3d9293 doc_id: 980452 cord_uid: ybzvbygp BACKGROUND: As in many fields of medical care, the coronavirus disease 2019 (COVID‐19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT. METHOD: Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group (IT IG) set‐up a web‐based retrospective survey (SurveyMonkey®) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine. RESULTS: 417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID‐19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID‐19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). CONCLUSIONS: This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID‐19 pandemic and gave no concerns regarding reduced tolerability under real‐life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long‐lasting negative impact on the clinical care of allergic patients. whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID- 19 and/or a positive test result for severe acute respiratory Introduction This article is protected by copyright. All rights reserved A new strain of coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) was first reported in China in December 2019 and has led to coronavirus disease 2019 (COVID-19) of global relevance (1) . The disease has been diagnosed all over the globe and the World Health Organization (WHO) declared a pandemic in March, 2020 (2). To date, there are still limitations in diagnostic methods, epidemiological data and accuracy in treatments (3) (4) . The wide range of clinical presentations from asymptomatic patients to multi-organic disease adds uncertainty in the prognosis and evolution (5) (6) . Although the advances in the recognition of the disease and the prevention of a fatal evolution have been huge, there are still many open questions to be answered and further investigated (7) . This research facilitates the best approach to this new disease and the optimal management of patients in allergy clinics and practices (8) (9) (10). Social One of the most important therapies in allergic patients is allergen immunotherapy (AIT) as the only disease-modifying treatment option in IgE-mediated allergic diseases (26) (27) . AIT has been shown to decrease symptoms, reduce the risk of developing asthma in patients with allergic rhinitis and improve quality of life and also to have long-term efficacy after cessation of the three-year course of treatment (28) (29) (30) (31) . Current administration can be by subcutaneous (SCIT) injections or sublingual (SLIT) drops or tablets (32) (33) . The underlying mechanisms of tolerance induction have been investigated and better understood throughout recent This article is protected by copyright. All rights reserved years (34). However, the ongoing COVID-19 pandemic has raised some uncertainties regarding the safety of AIT treatment under the current circumstances. One early statement of the EAACI and the "Allergy and Its Impact on Asthma"(ARIA-)initiative outlined practical recommendations on AIT (23) . If COVID-19 is suspected or confirmed, all kinds of AIT should be temporally interrupted as a general rule in infectious diseases (33) (35) (36) . If the patient is free of symptoms without evidence of the disease, SLIT can be administered at home supported by telemedicine. This option can help in maintaining adherence to treatment as well as in follow up of allergic disease evolution and confirmation of absence of COVID-19. In an earlier clinical trial on SLIT in grass pollen-allergic Highly Active AntiRetroviral Therapy (HAART)-treated Human Immunodeficiency Virus (HIV)-positive patients were reported to be safe without any signal for any significant alteration of CD4-positive T-cell counts and HIV load (37) . Concerning SCIT, it should also be continued regularly in COVID-19 symptom free patients without evidence of the disease, especially if AIT is indicated for the treatment of life-threatening conditions such as venom allergy (23) . As visits to clinics can be postponed, the administration of SCIT in respiratory allergy can also be In total, the survey was answered by 417 physicians and allied health professionals. 69% of the respondents were EAACI members, 22% EAACI Junior-members and 9% non-EAACI members. Most were physicians in Spain (9%), Mexico (6%), Italy (6%), Turkey (5%), and in other countries (all <5%) ( Figure 1 , Supplementary material: Table S1 ). They worked in university hospitals (42%), followed by private practices (25%), public hospitals (18%), private hospitals (9%) and others. Most of the respondents were clinicians completely or partially committed to both pediatric and adult allergic patients (48%), followed by clinicians completely or partially Accepted Article committed to adult patients only (27%) or to pediatric patients only (20%), allied health professionals (2%) and others (2%). 68% of the respondents were allergists, followed by pediatricians (12%), Ear-Nose-Throat (ENT) specialists (5%), pulmonologists (5%), internal medicine specialists (3%), dermatologists (2%) and others. Most respondents (64%) had experience in AIT for more than 10 years (Supplementary material: Table S2 ). 44% reported having national guidelines or Position Papers/Consensus Statements, whereas 46% reported not to have these documents available on the national level. In addition, 42% of the respondents reported following national or international guidelines or Position Papers/Consensus Statements for the management of AIT during the COVID-19 pandemic in daily practice and 38% reported following a similar strategy as recommended in these guidances before being aware of these documents. 42% of the respondents reported that face-to-face visits were replaced by phone calls for follow-up consultations, but to maintain consultations in newly referred patients. In contrast, almost one out of three respondent (30%) informed having replaced all face-to-face consultations by phone calls as a general rule (Table 1) . In this category almost 60% of the respondents reported not to initiate SCIT for inhalant allergies for the induction phase of AIT but to postpone the start of SCIT after the lockdown. 16% answered to "switch" the route of allergen-application from SCIT to SLIT and only 10% having initiated SCIT as planned (under ordinary, non-pandemic circumstances). In patients with SCIT for venom allergies, still 40% of the respondents decided to postpone the treatment to a time-window after the pandemic and only 25% reported to initiate SCIT as planned under ordinary circumstances. For SLIT, 48% of the respondents informed having initiated this therapy as planned under regular circumstances (Table 2) . In patients without any current symptoms to suspect a COVID-19 infection, the onset of adverse reactions during AIT for inhalant allergies was reported by 4% of the respondents for SCIT and 6% for SLIT in the initiation phase of treatment whereas it was 2% for SCIT and 4% for SLIT in the maintenance phase (Table 3) . 16 out of 305 respondents answering this part of the questionnaire reported having treated patients despite (early) symptoms of COVID- 19 and/or positive test result for a SARS-CoV-2 infection (Table 4 ). During the initiation phase of SCIT significant adverse events were reported by one physician, whereas the remaining informed that SCIT was well tolerated without increased rates of adverse events. For SLIT all respondents informed that no adverse events developed in this particular subgroup of patients treated. During the maintenance phase of AIT treatment, significant adverse events have been reported by one respondent for SCIT again whereas this has not been noted for SLIT-treated patients (Table 5) . The survey ended by indicating the respondents' opinions about next strategies regarding the future management of AIT for the second half of 2020 ( Figure 3 ). This article is protected by copyright. All rights reserved To the authors' knowledge, this is the first report of practical aspects and safety of AIT in a real-world setting under the current COVID-19 pandemic. Other surveys have been launched in order to understand the perception and the impact of the pandemic on patient care and decision-making in other medical disciplines such as e.g., urology, neurology and pneumology (39) (40) (41) (42). This is the first report of an international survey in the field of atopic diseases with a special focus on AIT. More than 400 physicians and allied health professionals from all over the world have This article is protected by copyright. All rights reserved before becoming aware of the international guidances (Table 1) . This fact can be explained by the broad expertise of the participating physicians on AIT and their compliance in following evidence-based recommendations in AIT guidelines in general (31) (28) . Telemedicine such as phone-calls or videoconferences has been demonstrated as a convenient and sufficient opportunity to interact with patients remotely in certain situations e.g. to improve patient-adherence to treatment in general (46) , but also to optimize care of allergic patients (17) especially in the current pandemic (16) . As such, this form of consultation is an ideal tool to differentiate between allergic symptoms and COVID-19 symptoms, to triage potentially infected patients accordingly as well as to optimize and prioritize treatment in the current pandemic. Adherence to sublingual treatment in AIT as well as accuracy in self-application of biologics, have met an excellent tool in telemedicine for its follow-up and support (9) (22) . The high number of more than 40% of respondents deciding to replace face-toface visits by remote follow-up consultations ( This article is protected by copyright. All rights reserved Remarkably almost 60 % of the respondents indicated to postpone the initiation of SCIT to a time point after the pandemic ( Our analysis has revealed that only one tenth of the prescribing physicians initiated SCIT as it would be planned under regular circumstances, whereas in SLIT this was decided by every 2 nd prescriber. One possible reason for the latter could be that physicians may trust more in the general safety of SLIT than SCIT especially in the initiation phase of treatment. This fact is also mirrored in 16% of physicians switching the application route from SCIT to SLIT (Table 2) (Table 2) . Moreover, 40% of the respondents decided to pause this treatment and postpone the begin to a time point after the current pandemic. The This article is protected by copyright. All rights reserved underlying background can only be speculated: one reason may be the need for in person consultations in the practice/clinic to receive the injections. AIT for venom allergy is the most effective treatment for patients with venom-allergies with much evidence supporting this treatment (30) American experts strictly recommends the initiation of SCIT in venom allergic patients as an "essential service" (8) . However, the undertreatment revealed by this analysis undoubtedly may have This article is protected by copyright. All rights reserved During the induction phase a low number of significant adverse-events, were reported for SCIT (3%) and SLIT (6%) in healthy patients and even less in the maintenance phase of AIT (Table 3) . Taken together these analyses support data from clinical trials and real-world-evidence regarding the safety of AIT in principle when treatment-strategies are compliant with international guidelines in AIT (28) (35) . A systematic meta-analysis of the EAACI demonstrated a comparable safety profile for both application forms of AIT, but could not differentiate between the initial induction and maintenance phase (55) . Also, to the non-interventional nature of the retrospective analysis reported here, this survey was not able to classify adverse events in international, standardized gradings. However, it can be concluded that the data set did not indicate a signal for diminished safety of AIT during the current pandemic, in patients without clinical signs of COVID-19 or positive test results of The third domain of the questionnaires investigated the safety of AIT in patients despite (early) symptoms of COVID-19. In the EAACI Position Paper (23) as well as in the German adaption (43) AIT temporary discontinuation of both SCIT and SLIT is recommended in these patients. Also, in this scenario a consensus statement of the This article is protected by copyright. All rights reserved Italian Society of Pediatric Allergy and Immunology indicated immediate interruption of AIT (14) . The same is recommended in an Asian article by Lee et al., stating that AIT should not be re-administered until complete resolution of infection or test results are negative (56) . The majority of respondents in our survey followed these recommendations as common rules (Table 4) . Interestingly, those respondents informing that AIT was not interrupted have indeed not flagged-up a significant increase of adverse events in this subset of patients with a potential for an increased risk ( Table 5) This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. 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