key: cord-307248-8e34ndn4 authors: Klimek, Ludger; Jutel, Marek; Akdis, Cezmi; Bousquet, Jean; Akdis, Mübeccel; Bachert, Claus; Agache, Ioana; Ansotegui, Ignacio; Bedbrook, Anna; Bosnic‐Anticevich, Sinthia; Canonica, Giorgio W; Chivato, Tomas; Cruz, Alvaro A; Czarlewski, Wiencyslawa; Giacco, Stefano Del; Du, Hui; Fonseca, Joao A; Gao, Yadong; Haahtela, Tari; Hoffmann‐Sommergruber, Karin; Ivancevich, Juan‐Carlos; Khaltaev, Nikolai; Knol, Edward F; Kuna, Piotr; Larenas‐Linnemann, Desiree; Melen, Erik; Mullol, Joaquim; Naclerio, Robert; Ohta, Ken; Okamoto, Yoshitaka; O’Mahony, Liam; Onorato, Gabrielle L; Papadopoulos, Nikos G; Pawankar, Ruby; Pfaar, Oliver; Samolinski, Boleslaw; Schwarze, Jurgen; Toppila‐Salmi, Sanna; Shamji, Mohamed H.; Ventura, Maria Teresa; Valiulis, Arunas; Yorgancioglu, Arzu; Matricardi, Paolo; Zuberbier, Torsten title: Handling of allergen immunotherapy in the COVID‐19 pandemic: An ARIA‐EAACI statement date: 2020-04-24 journal: Allergy DOI: 10.1111/all.14336 sha: doc_id: 307248 cord_uid: 8e34ndn4 The current COVID‐19 pandemic influences many areas of social life, medical treatments and the way allergy is performed. Allergen‐specific immunotherapy (AIT) is one of the most important treatment options for IgE‐mediated allergies and is based on immunological effects on the diseased patient The current COVID-19 pandemic influences many areas of social life, medical treatments and the way allergy is performed. Allergen-specific immunotherapy (AIT) is one of the most important treatment options for IgE-mediated allergies and is based on immunological effects on the diseased patient. This manuscript outlines the EAACI recommendations regarding AIT during the COVID-19 pandemic and aims at supporting allergists and all physicians performing AIT in their current daily practice with clear recommendations how to perform treatment during the pandemic and in SARS-CoV-2 infected patients. The World Health Organization (WHO), on March 11, 2020, declared a pandemic of an infectious disease recently referred to as "coronavirus disease 2019" . COVID-19 presents with many different clinical manifestations, ranging from asymptomatic cases to mild and severe disease, with or without pneumonia(4). This article is protected by copyright. All rights reserved diabetes mellitus, coronary artery disease and immunodeficiency of different origins are listed as risk factors for severe illnesses, hospitalization and death (4) (5) (6) 8) . As COVID-19 is caused by a newly identified viral strain, there are no therapeutics proved to be effective in clinical trials or vaccines, so far, and there is presumed to be no pre-existing immunity in the population (9) . In most instances, coronaviruses are believed to be transmitted through large respiratory droplets from person to person, through inhalation or deposition on mucosal surfaces. Other routes implicated in the transmission of coronaviruses include contact with contaminated fomites and inhalation of aerosols produced during aerosol-generating procedures, such as sneezing or coughing. The SARS-CoV-2 virus has been detected in respiratory, faecal and blood specimens(10). The highest risk of healthcare-associated transmission occurs in the absence of standard precautions, when primary infection prevention and control measures for respiratory infections are not in place, and when handling patients whose COVID-19 diagnoses is yet to be confirmed. Since airborne transmission is possible, we recommend a cautious approach because of possible transmission through aerosols (11, 12) . More disease background information is available online from the European Centre for Disease Prevention and Control (ECDC) (13) , WHO(14)) and the ECDC's Rapid Risk Assessment (9) . AIT is the onlydisease-modifying therapy that confers a long-term clinical benefit for allergic airway diseases such as in allergic bronchial asthma or allergicrhinoconjunctivitisand other allergic conditions (15) . Since its(16)emergence over hundred years ago (1911), AIT is an established and internationally recognized procedure for the causal treatment of immediate-type allergic reactions (type I allergy) and associated diseases. AIT induces an immune tolerance responses against the allergen in sensitized patients (17) . Systematic reviews and meta-analyses have confirmed that AIT is effective in reducing symptomstogether with rescue medication in patients with allergic asthma (18)and allergic rhinoconjunctivitis (19) . This applies to both, subcutaneous immunotherapy (SCIT) (20, 21) and sublingual This article is protected by copyright. All rights reserved immunotherapy (SLIT), liquid drops or tablets placed under the tongue (22) . Thereducedriskof developing asthma in patientswith allergic rhinitis is another advantage of AIT, that is still under debate but was demonstrated to be at least effective in the short term(23, 24) . AIT is also effective in patients withIgE-mediated food allergy(23-26)and insect venom allergy (27) .Moreover, analyses bythe European Academy of Allergy and Clinical Immunology (EAACI) demonstrated the cost-effectiveness of this diseasemodifying therapy option (28) (29) (30) . Eventhough it is well established that allergic airway diseases are associated with an Highly active antiretroviral treatment has improved the immune function and life expectancy in HIV-infected patients whose respiratory allergic incidence is similar to that of the general population (33) . Clinical efficacy data showed a significant improvement in SLIT-treated patients compared to controls but not any considerable alteration of peripheral T CD4 lymphocyte cell counts and HIV viral load in both groups. These data showthat SLIT therapy in viro-immunological controlled HIV positive patients was efficacious, safe and well-tolerated. Cytomegalovirus (CMV) was shown to enhance the allergenic potential of otherwise poorly allergenic environmental protein antigens ina mouse model of airway co-exposure This article is protected by copyright. All rights reserved to CMV and ovalbumin (OVA) (34) . In contrast, immune reactions to Virus-like-particles (Vlp) may enforce the immune responses in AIT and may even be used as AIT adjuvants for inhalational and food (peanut) allergen in the near future (35, 36) . With the limited experimental data available so far, it seems that patients with allergic rhinitis did not develop additional distinct symptoms and more severe courses than other patients (4) . Allergic children showed a mild course, similar to other children (4) . AIT aims to induce allergen-specific immune tolerance in allergy patients by using This article is protected by copyright. All rights reserved severe COVID-19 cases and a major reason for acute respiratory distress syndrome (ARDS) and multi organ failure. Several levels of evidence suggest that the rapid COVID-19 mortality might be due to a virus-activated "cytokine storm syndrome" (43) .In a study of Allergen-specific antibody levels change in the course of AIT with decreased specific IgE in the long run and a relatively rapid increase in specific IgG1 and IgG4 (29, 45) . In COVID-19 like many viral infections SARS-CoV-2-specific IgM increases in the acute phase followed by specific IgG (46) (47) (48) . Overall, theCOVID-19 immunological mechanisms seem to be similar to SARS and MERS and also to severe influenza infections. An appropriate anti-viral immune response should develop with cytotoxic T cells and IgM and IgG antibodies, whereas a very strong uncontrolled immune response as in a cytokine storm, becomes detrimental (Table 1) . We This article is protected by copyright. All rights reserved To maximize the use of PPE if there is an insufficient supply, staff should be assigned to carry out procedures, or a procedure, in designated areas(52). AIT is a treatment, that requires recurrentdoctor/nurse/patient contact over a more extended period, e.g. 3 years. In SCIT, injections are administered with daily, weekly (up dosing phase) or monthly (continuation phase) intervals. In SLIT, the initiation is given in allergy clinics or in a doctor´s office, while continuation is performed by patients themselves with regular control visits. Each SCIT or SLIT product needs approval by the competent authority. It must contain information on how to use the AIT product for patients, allergologists and nurses. For This article is protected by copyright. All rights reserved most products authorized in Europe, instructions for use recommend that patients experiencing an acute respiratory tract infection should temporarily discontinue AIT treatment until the infection is resolved. We recommend taking similar action in COVID- 19 . Confirmed cases should discontinue AIT, both SCIT or SLIT, independent ofdisease severity until the symptoms have completely resolved and/or an adequate quarantine has been performed. The possibility of expanding injection intervals in the continuation phase may be beneficial. In patients, who recovered from COVID-19 or who are found to have a sufficient SARS-CoV-2 antibody response after (asymptomatic) disease (14), AIT can be started or continued as planned. AIT can also be continued as usual in patients without clinical symptoms and signs of COVID-19 or other infections and without a history ofexposure ot SARS-CoV-2 or contact to COVID-19 confirmed individualswithin the past 14 days. SLIT offers the possibility of taking it at home, thus avoiding the need to travel to or stay in an allergy clinic or doctor's office, which would be associated with a risk of infection. Interrupting subcutaneous immunotherapy is not advised. Especially in potentially life-threatening allergies, such as venom allergy, SCIT should be regularly continued. The possibility of expanding injection intervals in the continuation phase should be checked and may be beneficial. Interrupting sublingual immunotherapy is not advised. Supply the patient with sufficient medication for a minimum of a 14 days quarantine. Sublingual immunotherapy can be taken at home. The intake of SLIT by the patient at home or any place is advantageous in avoiding contact to potentially infected persons. 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