COVID‐19 in severe asthmatic patients during ongoing treatment with biologicals targeting type 2 inflammation: Results from a multicenter Italian survey

Abstract

To the Editor, Several reports describe an higher risk for viral infections in patients with asthma.1, 2 Novel coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that shows a predilection to infect the lower and upper airway tract, thus creating an higher clinical issue in asthmatic patients.3 Data about the prevalence and severity of COVID-19 in asthma patients are very scarce, and no conclusive evidence is available.4 Additional concerns about the effects of asthma medications on SARS-CoV-2 infection may arise, and data about severe asthma during ongoing biological treatment in COVID-19 pandemic are lacking. A cross-sectional telephone-based survey was performed in six asthma centers of five different regions located in Northern and Center Italy (Emilia-Romagna, Liguria, Lombardy, Tuscany, Veneto) between April 1st, 2020 and April 20th, 2020. Adult severe asthma patients, with ongoing treatment with biological therapy actively followed at the above reported centers, were eligible. All the 473 eligible patients were successfully contacted, and none declined the interview. During the telephone call, each patient received questions reported in Appendix S1. The study was approved by the Local Ethical Committee (17423_OSS). No statistical sample size calculation was performed a priori. Quantitative parameters are expressed as the mean, and qualitative parameters are expressed as frequencies and percentages of the corresponding population. The prevalence of SARS-CoV-2 infection was expressed as the percentage (with 95% confidential interval [CI]) of cases with infection confirmed by nasopharyngeal swab on the total number of patients included in the study. This proportion was compared to that reported for the geography-matched Italian population, by using the chi-square test. A P value of <.05 was considered statistically significant. The mean age of the study population (M/F: 214/259) was 55 ± 12 years. Most of them (61%) were atopic and were suffering from chronic rhinosinusitis (74.4%). Sixty-three patients (13.3%) have bronchiectasis described on chest computed tomography. Other co-morbidities included diabetes (5.3%) and hypertension (21.6%). Among the latter group, 81 patients (79.4%) were receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). A proportion of our study population (n = 87, 18.4%) has been continuing the usual life activities at work during pandemic, or have interrupted working activity (n = 124, 26.2%) or were shifted to smart working (n = 70, 14.8%). The remaining patients (n = 192, 40.6%) were housewife, retirees or unemployed. All included patients were receiving Step-5 treatment according to GINA guidelines. A proportion of them (n = 99, 20.9%) had been taking a stable dose of prednisone or equivalent (range 2.5-7.5 mg/day). Included patients have been receiving omalizumab (n = 145, 30.6%), mepolizumab (n = 200, 42.3%), benralizumab (n = 124, 26.2%) or dupilumab (n = 4, 0.8%) for 21 months (median) (Table 1). All (n = 473) Benralizumab (n = 124) Dupilumab (n = 4) Mepolizumab (n = 200) Omalizumab (n = 145) Fifteen patients had undergone nasopharyngeal swab for reported symptoms compatible with SARS-CoV-2 infection. Four out of them tested positive (confirmed COVID-19), while 11 tested negative (probable COVID-19). Three out of the four confirmed cases have had contact with other COVID-19 cases. The proportion of patients in the survey population that were tested was 3.17% (15/473) and was similar to that reported in an age- and geography-matched population (3.21%). The prevalence of laboratory-confirmed SARS-CoV-2 infection was 0.8% (95% CI 0.230-2.150), and no difference was observed in comparison to data in an age- and geography-matched population that indicate a prevalence of 0.8% (95% CI 0.797-0.804) (Table 2). All nine patients with compatible symptoms, but not analyzed with nasopharyngeal swab, recovered from symptoms without need for hospital admission. During the COVID-19 pandemic, all 473 patients have maintained biological therapy. Three COVID-19 patients were receiving omalizumab, and one was receiving benralizumab; all of them were atopic patients. The four confirmed COVID-19 cases displayed a good control of asthma symptoms before SARS-CoV-2 infection, without asthma exacerbations during the last 3 months before illness. Three out of them paused the therapy during illness. Two SARS-CoV-2 infected patients experienced a mild COVID-19, while two patients required admission to the intensive care unit for severe and critical illness, respectively. All of them clinically recovered. The four cases of COVID-19 are individually described in Table 3. Region of Italy Age, gender, BMI Tuscany 45, M, 33 Veneto 71, M, 27 Veneto 39, M, 30 Emilia-Romagna 47, F, 31 Fever, Dyspnea, Anosmia Fatigue Fever Dyspnea Diarrhea Fatigue Fever Cough Fatigue O2 Supplement Duranavir Tocilizumab HCQ Azithromycin LMWH O2 Supplement HCQ Azithromycin 6MP Azithromycin HCQ Our report has some limitations. No systematic testing was undertaken in the population studied, thus reducing the accuracy of the epidemiologic data. However, the proportion of the asthmatic patients tested for SARS-CoV-2 was similar to that reported in the geography-matched general Italian population. The social distancing measures applied in Italy since March 9th may have put the patients at reduced risk of being exposed to SARS-CoV-2, even if a proportion of them has been continuing the usual life activities at work; additionally, centers located in area with a high prevalence and lethality of SARS-CoV-2 infection5 were involved and clinical data related to the previous 3 months were collected. However, the true prevalence may be under-reported also because of the asymptomatic cases and of new cases possibly occurring after our report. Lastly, we cannot exclude additional protective measures adopted by asthmatic patients. The availability of virus-specific antibody testing could clarify whether the low prevalence of COVID-19 in this cohort reflects a reduced risk or a reduced exposure to SARS-CoV-2 infection. Emerging data suggest that allergic status may reduce the risk for SARS-CoV-2 infection,3, 6 but raises concerns regarding the use of biological targeting type 2 inflammation in the context of COVID-19 pandemic. Eosinophils have been shown to have anti-viral activity7 and eosinophenia occurs in SARS-CoV-2 infected patients.8 In our survey population, only one out 324 patients that were receiving treatment interfering with eosinophils and IL-5-biology (mepolizumab and benralizumab) developed COVID-19. Although further investigations are needed, this data might appear to be reassuring about the consequences of drug-induced eosinophenia at the times of COVID-19 pandemic. Older age, diabetes, and hypertension are well-recognized risk factors for lethality in COVID-19.9 A high proportion of study population was over 65 years of age, and about 17% of patients were receiving therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), but these factors appear irrelevant in our study population. Lastly, none of COVID-19 patients belongs to the subgroup of asthmatics with bronchiectasis, in fact these mainly experience bacterial infections. In summary, even if this study does not allow any definitive conclusion on the association between severe asthma, biological therapy, and SARS-CoV-2 infection, it might suggest that severe asthma patients during ongoing treatment with biologicals targeting type 2 inflammation may not have an increased risk for COVID-19, in comparison with age- and geography-matched nonasthmatic population. We underline that all analyses in this survey should be regarded as descriptive and that retrospective or prospective studies analyzing cohorts of SARS-CoV-2 infected patients are needed to confirm the lack of association between asthma and COVID-19 and to explore the potential relevance of biologics in modulating the immune susceptibility to COVID-19. None of the authors has a financial or any other conflict of interest to disclose. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Topics & Concepts