Julia Zarnowski1, Paula Kage2, Jan-Christoph Simon2, Regina Treudler2. 1. Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, Germany. Electronic address: julia.zarnowski@medizin.uni-leipzig.de. 2. Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, Germany.
In the beginning of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, chronic airway diseases were discussed to be risk factors for a severe outcome of COVID-19, as epithelial barrier dysfunction in allergic rhinitis or asthma was suspected to increase susceptibility for SARS-CoV-2 infection, potentially leading to increased symptoms or prolonged recovery.
,This was based on previous investigations revealing pollen exposure can decrease immune defense against respiratory viruses.
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Moreover, high airborne pollen concentrations were correlated with increased SARS-CoV-2 infection rates, whereas pollen or particulate matter was not found to serve as transmitters for viral particles.
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Studies have revealed that TH2-dominated diseases are associated with lower viral defense mechanisms owing to a reduced antiviral interferon response, altogether increasing the susceptibility for respiratory viral infections or even systemic infections in patients with atopy.
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Several international studies, however none from Germany, have investigated possible effects of atopic disorders on COVID-19 disease and recently even a protective effective was supposed.
,In a retrospective, questionnaire-based study, we aimed at analyzing the impact of atopic diseases on the course and severity of COVID-19 in adult patients with confirmed SARS-CoV-2 infection in our region. Patients were recruited after identification by the local health authorities or when presenting at the Department of Allergology of our university hospital. All subjects had SARS-CoV-2 infection before the local rise of mutant B1.1.7.A total of 107 patients were included, of whom 53 (49.5%; mean age, 44.4 years) presented a history of symptomatic atopic diseases in the past 12 months whereas 54 subjects without atopic history served as controls (50.5%; mean age, 44.5 years). Characteristics of 107 patients are given in Table 1
. Baseline data revealed no significant differences between atopic (group 1) and nonatopic subjects (group 2) with regard to sex or age. In group 1, 8 of 53 patients (15.1%) had atopic dermatitis, 47 of 53 patients (88.7%) had allergic rhinoconjunctivitis, and 14 of 53 patients (26.4%) had allergic asthma. All patients had a known sensitization to inhalative allergens. In regard to plant-derived allergens, grass (64.2%) and birch (50.9%) pollens were reported most frequently, and sensitization to nonherbal allergens were most often to mites (34%), cat (30.2%), or dog (18.9%) allergen. In group 1, 5 patients (9.4%) received allergen-specific immunotherapy when COVID-19 infection occurred. In addition, 9 of 53 patients (17%) were treated with local or systemic immunosuppressive medications (n = 3 topical nasal steroids, n = 4 steroid ointment, n = 6 inhalative steroids, n = 1 cyclosporine, n = 1 methotrexate and etanercept). In group 2, only 1 patient had omalizumab owing to chronic urticaria, although no other immunoactive drugs were reported to be taken.
Table 1
Demographic data, reported symptoms and regeneration time in atopic (group 1) and non-atopic (group 2) patients
Group 1 (atopy)
Group 2 (controls)
Significancea
n
53
54
Female
24 (45.3%)
28 (51.9%)
0.50
Age (y), median (range)
42 (31-52)
43 (33-58)
0.92
Symptomatic
52 (98.1%)
52 (96.3%)
0.57
Asymptomatic
1 (1.9%)
2 (3.7%)
Quarantine only
50 (94.3%)
51 (94.4%)
0.98
Outpatient care
4 (7.5%)
3 (5.6%)
0.68
Hospitalization
3 (5.7%)
3 (5.6%)
0.30
Oxygen supply
None
2 (3.7%)
0.16
Experienced symptoms
Fever
29 (54.7%)
22 (40.7%)
0.15
Smell or taste
33 (62.3%)
35 (64.8%)
0.78
Gastrointestinal
15 (28.3%)
8 (14.8%)
0.09
Skin changes
4 (7.5%)
6 (11.1%)
0.53
General symptoms
47 (88.7%)
42 (77.8%)
0.13
Myalgia
33 (62.3%)
29 (53.7%)
0.37
Headache
35 (66%)
32 (59.3%)
0.47
Rhinorrhea
20 (37.7%)
25 (46.3%)
0.37
Pulmonary symptoms
31 (58.5%)
31 (57.4%)
0.91
Dry cough
26 (49.1%)
27 (50%)
0.92
Productive cough
3 (5.7%)
7 (13%)
0.20
Shortness of breath without oxygen supply
11 (20.8%)
8 (14.8%)
0.42
Shortness of breath with oxygen supply
0
1 (1.9%)
0.32
Self-reported regeneration time
<2 wk
39 (73.6%)
37 (68.5%)
0.565
>2 wk
14 (26.4%)
17 (31.5%)
Mann-Whitney U test.
Demographic data, reported symptoms and regeneration time in atopic (group 1) and non-atopic (group 2) patientsMann-Whitney U test.Statistical analysis did not reveal a significant difference in experienced symptoms, treatment regimen, or recovery time between both groups. Furthermore, patients with atopy receiving immunotherapy or immunosuppressive medication did not have any significant differences for any of the parameters investigated. Hospitalization rates were comparable in both groups with n = 3, respectively (5.7% and 5.6%).In conclusion, our data support the evidence that atopic comorbidities have no unfavorable impact on severity and course of COVID-19. Several studies have analyzed the effect of atopic diseases on the expression of Angiotensin-converting enzyme 2 (ACE2) or transmembrane protease 2, which induces the receptor binding of SARS-CoV-2.
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It was found that I"?>interleukin 13 (IL)"?>, most often overexpressed in the context of TH2 inflammation, can significantly down-regulate ACE2 expression.
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Respiratory allergies, elevated I"?>immunoglobulin E (IgE) "?>levels, and topical and inhalative corticosteroids were also associated with a decreased ACE2 expression.
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Altogether, this implicates that a decreased ACE2 expression in atopic manifestations may potentially reduce viral entrance of SARS-CoV-2 and thus lowers susceptibility for COVID-19 infection or disease severity in individuals with atopic background.
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,As severe COVID-19 cases have been associated with eosinopenia, previous studies have discussed a potential antiviral role of eosinophils in the immune system.
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In terms of their function in innate immunity, eosinophils are capable of antigen presentation and recognition of viral particles and release of proinflammatory mediators through degranulation and promotion of type 2 cytokines. Atopic diseases are often associated with elevated eosinophil levels, which can be induced by the TH2-derived cytokine interleukinIL"?> 5. An increased antiviral immune response in SARS-CoV-2–infected patients with atopy with eosinophilia may be speculated, but further analysis is needed. With regard to most often prescribed medication, inhalative, intranasal, or systemic corticosteroids and allergen-specific immunotherapy have beneficial effects for local viral defense. Furthermore, large-cohort analyses of patients with severe asthma have revealed that risk of infection, course of COVID-19 disease, or mortality is not increased when patients require treatment with biologicals. Clinicians should be aware that patients who have atopic diseases might stop taking their effective medication as they fear severe COVID-19 illness, but owing to the potential benefit of these therapies, an unnecessary discontinuation should be avoided, requiring good clinical care and patient education.
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