Allergen immunotherapy during the COVID‐19 pandemic—A survey of the German Society for Allergy and Clinical Immunology

Abstract Background When the coronavirus pandemic 2019 (COVID‐19) emerged, concerns were also raised regarding the safety of allergen immunotherapy (AIT). The German Society for Allergology and Clinical Immunology (DGAKI) conducted a survey to collect real‐world data on the daily routine of administering subcutaneous AIT (SCIT) and sublingual AIT (SLIT) during the COVID‐19 pandemic. Methods A web‐based retrospective survey using the online platform survio with 26 standardized questions was used to survey physicians treating allergic patients during the pandemic. Results Three hundred and forty‐five physicians who regularly offer and perform AIT in German‐speaking countries responded to the questions. 70.4% of the respondents stated that they regularly initiated and dosed up SCIT for inhalant allergies (41.4% venom‐SCIT, 73.6% SLIT), and 85.2% of the respondents stated that they continued SCIT for inhalant allergies during the maintenance phase in a regular way (59.1% venom‐SCIT, 90.4% SLIT) in healthy patients without current symptoms indicating an infection with COVID‐19. With regard to tolerability, there was no evidence for increased occurrence of adverse events in patients without current symptoms of COVID‐19 infection during the pandemic. Conclusions This retrospective study demonstrated adherence to national and international position papers of AIT during the COVID‐19 pandemic in German‐speaking countries. Besides, the survey has confirmed a good tolerability of AIT for both SCIT and SLIT.

declared to be pandemic in March, 2020. [1][2][3][4] Despite the fact that a variety of viral and bacterial infections are known to trigger or aggravate exacerbations in asthmatic patients, initial analyses did not show an increased risk for severe courses of SARS-CoV-2 infections in allergic patients. [5][6][7] However, data were limited and inconclusive at the beginning of the pandemic. The European Academy of Allergy and Clinical Immunology (EAACI), but also national societies, therefore published several position papers, [8][9][10] how to manage optimal care of allergic patients and allergen immunotherapy (AIT) during the so called "first wave" of the pandemic.
AIT is a disease-modifying treatment option for various allergic diseases and can be administered subcutaneously (SCIT) or sublingually (SLIT). [11][12][13][14][15] It provides long-term benefits, if adherence is ensured. 16,17 Though AIT generally is a safe and effective treatment option in allergic diseases, uncertainties regarding the safety of this treatment arose in the context of the COVID-19 pandemic.
Among these, treatment providers struggled to prioritize face-toface encounters considering the recommendation to avoid social contact. 18 However, continuation of therapy is generally recommended in the aforementioned international position papers [8][9][10] as well as in the previously adapted national versions for Germanspeaking countries. 19,20 Therefore, a triage for example, via telephone should be performed to identify patients with symptoms of COVID-19 prior to consultation in order to minimize the risk of infection. Initiation of SCIT or SLIT in patients, without known COVID-19 infection or symptoms indicating such, is generally possible according to the recommendations adapted to Germanspeaking countries. 19,20 However, a thorough history and examination for signs of infection at the start of treatment and at each subsequent SCIT injection or SLIT administration is recommended. 19 Regarding continuation of AIT, SCIT in particular, should be continued, especially for potentially life-threatening allergies such as insect venom allergy. Lengthening the injection intervals may be considered. Termination of SLIT is also unlikely to be necessary. 19,20 However, it remains unclear whether continued AIT in the setting of COVID-19 infection is safe and data are lacking. In general, interruption of AIT is indicated when viral infections occur, therefore experts recommend discontinuing AIT in case of COVID-19 infection as well. 8,9,20,21 Based on the international consensus, EAACI previously conducted a survey to analyse the situation in different countries worldwide regarding the implementation of AIT in routine clinical practice. 18 Since national position and consensus papers for Germanspeaking countries have followed, the German Society for Allergology and Clinical Immunology (DGAKI) conducted the present survey based on the international EAACI study with a special focus on the German-speaking countries Germany, Austria and Switzerland. The aim of the survey was to determine adherence of the practitioners to the published recommendations and to obtain further information on practical aspects and the general tolerability of AIT during the pandemic. Based on these data, valuable conclusions can be drawn regarding measures to manage AIT in this or in further potential pandemics in the future. Most of the respondents treated both pediatric and adult allergic patients (70.4%), followed by doctors treating mainly adult patients (22.3%) and doctors treating only children (7.2%). In terms of specialties, ear nose throat (ENT) physicians were the largest responding speciality with 68.3%, followed by dermatologists (18%), pulmonologists (6.7%), paediatricians (6.1%), and internists (4.1%). Overall 47.4% of the respondents reported being allergists (allergy is a subspecialty in Germany).

| METHODS
Most respondents had more than 10 years of experience in performing AIT. Physicians were asked how many percent of their patients with allergic rhinoconjunctivitis (ARC), asthma, or both concurrent conditions received AIT. Regarding ARC, 53,8% reported treating 50%-80% of their allergic patients with AIT. Similar results were obtained for patients with asthma and in cases of concomitant ARC and asthma. Furthermore, respondents were asked to indicate how many of their allergic patients with ARC received SLIT or SCIT in percentage (in total 100%). The majority of respondents indicated that they treated more patients with SCIT than with SLIT.
It was further examined whether the practitioners were aware of position papers for conducting AIT during the pandemic. In total, 72.5% of respondents stated that those were available, 8.7% indicated no available position papers and 18.8% did not know if those were available. Among all respondents, only 8.7% reported following national or international position papers or other recommendations when conducting AIT during the COVID-19 pandemic. However, 68.3% reported following a similar strategy prior to publication of the position papers. 9.3% of respondents followed an alternative strategy (Table 1).
Respondents were further asked to specify how they had practiced care of their allergic patients during lockdown. Most of the respondents (73.9%) stated that they maintained regular in person follow-up consultations. 19.7% followed an individual strategy, for example, continuation of therapy that has previously been initiated but no further treatment initiations. 2.6% of the respondents reported to have completely suspended follow-up treatments by replacing them by telephone consultations but have continued to perform initial treatments on site. Both initial and follow-up treatments were completely replaced by telephone consultations by 2.0% of respondents, while 1.7% indicated they had completely suspended initial and follow-up treatments (Table 1).

| Domain 2, Questions 12-21
Physicians were questioned regarding their strategy concerning AIT in patients without signs of COVID-19 infection. Regarding SCIT, regular up-dosing phase was performed by 70.4% of the respondents. 16.2% did not initiate SCIT and planned to postpone the initiation until after the pandemic. Another 5.5% reported SCIT-initiation with a modified therapeutic scheme (e.g., fewer visits for the up-dosing phase). 1.7% of the respondents decided to switch from SCIT to SLIT. In case of patients receiving SCIT for venom allergies, 41.4% of the respondents decided to perform regular treatment schedule, while 13.0% postponed treatment. 2.6% of respondents initiated SCIT, but modified the therapy regimen (e.g., shorter inpatient updose). 42.9% reported other. Most of these respondents did not have any requests for SCIT for venom allergy during the pandemic or they did not perform this treatment in the first place. Regarding SLIT, 73.6% of respondents started therapy under regular circumstances, whereas 12.2% reported delayed initiation. 2.0% of the respondents initiated therapy with modified up-dosing. 12.2% disclosed via commentary function not to perform SLIT (Table 2).  (Table 3). PFAAR ET AL.

| Domain 4
Respondents were asked to rate statements assuming a "second wave" in autumn/winter 2020. The statements were to be rated on a scale from 0 to 5. 0 corresponded to "I disagree" to 5 ″I agree to the fullest". The first statement was "In general, AIT should be paused because the risk of adverse side effects of AIT poses an unacceptable risk to patients." 83.5% of the respondents disagreed (by giving "0" points). The fourth statement was "In general, AIT should be changed from SCIT to SLIT." 70.7% of the respondents disagreed (by giving "0" points).
The fifth statement was "In general, AIT should 72 only be performed in specialized centres/outpatient clinics," and 62.9% of the respondents disagreed (by giving "0" points).

| DISCUSSION
This report is based on a previous EAACI international survey on the practical aspects and safety of AIT in the context of the COVID 19 pandemic. 18 As the EAACI/Allergic Rhinitis and Its Impact on Asthma The previous international survey referred to above found that almost 50% of respondents reported a lack of academic recommendations on AIT during the pandemic at national level. However, 41.91% felt that the available position papers were helpful and 38.15% stated following a similar strategy prior to becoming aware of those recommendations. 18 In total about 80% of the interviewed physicians performed therapy of allergic patients in line with the recommendations in the international position paper. The authors of the survey have attributed this to the expertise and evidence-based approach of physicians performing AIT. 18,22 In the current survey in the German-speaking countries, most respondents (72.5%) indicated that position papers were available at the national level. Even though only 8.7% stated following these, 68.3% indicated already following a similar strategy before getting aware of the recommendations. Hence, a total of 77% carried out the therapy in accordance to the "gold standard" as recommended in the  Furthermore, the use of telemedicine was encouraged to further minimize unnecessary contacts. 8,9,19,20 Telemedicine has been shown to be effective in allergic patient care and is a promising option for optimizing patient care in times of social contact avoidance. 23  pandemic. 24 This study revealed significant differences between participants from practitioners and clinicians regarding the perception of utility of telemedicine. Respondents from the outpatient sector attributed significantly lower relevance to telemedicine and utilized this opportunity less frequently, claiming regulatory restrictions. 24 Restrictions in health care occurred worldwide throughout the pandemic. A decline was also seen in the care of allergic patients, as the EAACI survey revealed that only 10% of the respondents initiated SCIT as usual. 18  With regard to AIT for insect venom allergy, the authors of the EAACI survey were particularly concerned, as 40% of respondents did not initiate it due to the pandemic. 18  practices. This could indicate that patients were more likely to visit practices during the pandemic. Moreover, outpatient practices might have been less affected by the pandemic in regard to capacity and resources. This assumption is supported by the results of the data from a survey among pneumologists. 24 According to this analysis, respondents from university hospitals and maximum care hospitals as well as regional hospitals perceived significantly higher changes in their daily work due to the COVID-19 pandemic than employees in the outpatient sector. 24  Moreover, most respondents disagreed that SCIT should be switched to SLIT and most of the interviewees disagreed that AIT should only be performed in specialized centres or clinics. This contradicts the EAACI survey. In the latter, about 50% agreed with this statement. 18 These results are not particularly surprising in respect of the population of physicians examined. As already mentioned, mainly physicians in outpatient practices with broad experience in this therapy answered the present survey. As other analyses, the present study indicates that practices might have been less affected by the pandemic and/or patients preferred treatment in the outpatient setting.