key: cord-0762394-go8mr01s
authors: Hanon, Shane; Brusselle, Guy; Deschampheleire, Maud; Louis, Renaud; Michils, Alain; Peché, Rudi; Pilette, Charles; Rummens, Peter; Schuermans, Daniel; Simonis, Hélène; Vandenplas, Olivier; Schleich, Florence
title: COVID-19 and biologics in severe asthma: data from the Belgian Severe Asthma Registry
date: 2020-12-03
journal: Eur Respir J
DOI: 10.1183/13993003.02857-2020
sha: dfdec41ab0eb00f151cd48e5c9e42d9d671b89c2
doc_id: 762394
cord_uid: go8mr01s

In a cohort of severe asthma patients, a small number of COVID-19 cases was found; none resulted in death or a very severe disease course. Use of biologics for severe allergic or severe eosinophilic asthma was not associated with a higher risk of COVID-19. https://bit.ly/3ndZmyD

266 (39%) of the 676 participants experienced at least one symptom suggestive of COVID-19 during the 4 months preceding the survey. Dyspnoea (n=172; 25%), rhinorrhoea (n=116; 17%), productive cough (n=107; 16%), headache (n=105; 16%) and chest pain (n=69; 10%), were the most frequently reported symptoms. Only 43 patients (6%) mentioned fever and only 35 (5%) of the patients experienced sudden olfactory and gustative dysfunction, symptoms that are considered quite specific for COVID-19 [14] , suggesting a low incidence of symptomatic COVID-19 in the study population.

Out of 676 patients, only 66 were tested by PCR on nasopharyngeal aspirates and nine (14%) tested positive for SARS-CoV-2 (table 1) . 40 (61%) PCR tests were performed because the patients presented suggestive symptoms, whereas the remaining tests were done in the context of healthcare or contact screenings. All the patients that had a positive PCR test had presented with suggestive symptoms. As the national restrictions with regard to PCR testing might have led to an underestimation of the true incidence of SARS-CoV-2 infection in patients with severe asthma in Belgium, serology testing to determine SARS-CoV-2 IgG antibody levels was performed, at the discretion of the treating physician, in a subgroup of patients that had presented a combination of symptoms suggestive of COVID-19. Positive IgG serology was found in only eight out of 98 tested patients. Of note, three of these patients who showed positive SARS-CoV-2 IgG had also demonstrated a positive PCR test. Because serology testing for COVID-19 only became available for large-scale clinical use towards the end of our study period ( June 2020), the number of cases identified by serology is probably also an underestimation of the true incidence. Overall, we identified 14 patients with COVID-19 infection confirmed by either PCR and/or specific IgG (table 1) . Of these 14 patients, only five (all PCR-positive) had been hospitalised (with a short hospital stay ranging from 2 to 8 days). None presented with a severe asthma exacerbation or required treatment with systemic corticosteroids, admission to the intensive care unit, non-invasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and there were no deaths. Only three patients received supplemental oxygen therapy (for 3 to 8 days). Chest computed tomography scan was performed in four hospitalised severe asthma patients and revealed pulmonary consolidations in three patients. Patients with confirmed COVID-19 reported a significantly higher median (interquartile range) number of symptoms than the remainder of the study population (6 (3-10) versus 2 (1-3); p<0.000001). Of the 35 patients that presented gustative or olfactory dysfunction, 24 were tested by means of PCR and/or serology and 10 (42%) were found positive, a finding that is consistent with these symptoms being considered more specific for COVID-19 [14] . Importantly, there was no difference in incidence of COVID-19 between severe asthma patients treated with biologics (anti-IgE or anti-IL5/anti-IL5R) and patients not receiving any asthma biologic ( p>0.05) (table 1), but as the number of confirmed cases is small, this has to be interpreted cautiously. Recent use of oral corticosteroids (OCS) has been identified as a risk factor for COVID-19 related death [11] , but in our cohort none of the 58 patients treated with maintenance OCS (median prednisone dose of 5 mg) were diagnosed with COVID-19.

To the best of our knowledge, this study is among the first to investigate the risk and severity of COVID-19 in a large cohort of well-characterised patients with severe asthma. The findings indicated a low incidence of COVID-19 infection in severe asthma patients (14 out of 676 patients; 2.1%). Nevertheless, it is difficult to compare the incidence rate of confirmed COVID-19 cases in our BSAR cohort to the figure in the general population. Analysis of blood samples from Belgian blood donors revealed a seroprevalence reaching up to 5.1% [15] . Our study showed that only 2.1% of patients with severe asthma in Belgium had positive PCR or specific IgG to SARS-CoV-2 and that only 5% presented COVID-19-related symptoms. Whether this relatively low incidence is due to those with severe asthma being more cautious than the general population and complying better with social distancing and other hygienic measures, or whether it is due to (patho) physiological features (type 2 inflammation) or beneficial effects of treatments such as ICS (the latter factors being associated with lower angiotensin-converting enzyme 2 expression) [16] remains to be elucidated.

Whereas viral respiratory tract infections are the most important cause of asthma exacerbations, none of the patients with confirmed COVID-19 in our BSAR cohort experienced an exacerbation. This is in line with the recent publication by BEURNIER et al. [1] reporting that, among hospitalised patients with severe pneumonia due to SARS-CoV-2 infection, patients with asthma were not overrepresented and did not present with an asthma exacerbation. The national restrictions with regard to PCR testing and the resulting possible underestimation of the true incidence of COVID-19 are a limitation of our study. Also, the participation in the survey of severe asthma patients already participating in a registry might have created some selection bias, limiting the generalisability of our data. On the other hand, the careful characterisation of the patients in our cohort is a strength of this research.

In conclusion, among this cohort of adult patients with severe asthma, a small number of COVID-19 cases was found, none of which resulted in death or a very severe disease course. Treatment with biologics for severe allergic or severe eosinophilic asthma was not associated with a higher risk of SARS-CoV-2 infection nor with more severe COVID-19. These data support the current practice to continue treatment with biologics in severe asthma during the COVID-19 pandemic.

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