To the editor;
We have read the article titled ‘Safety of biologics in severe asthmatic
patients with SARS‐CoV‐2 infection: A prospective study‘ by Sara Manti
et al. with great interest.1 Since the literature data
on the use of biologics in children are scarce, this study is very
valuable. Although the results of this study on biologicals are somewhat
consistent with the current literature, I have several
questions/concerns about their experience with these patients.
In this study,1 there are 21 patients (10 on therapy
with omalizumab, 9 with dupilumab, and 2 with mepolizumab). Twenty out
of 21 patients had a mild COVID‐19 course, and no adverse outcome was
observed. In this cohort of severe asthmatics treated with
biologics,1 hospitalization rate and/or poor outcome
of SARS-CoV-2 cases and their COVID-19 course was found much lower and
less severe when compared with other severe asthma registries (e.g.
Dutch and Belgian Severe Asthma Registry (BSAR), etc.) reported as
>65%.2-4 How do the authors explain this
discrepancy? It is not clear in the article.1 May the
effects of varying lockdown processes, different comorbidities, younger
study groups, the doses of biologics, and utilization period of
biologicals used in this study population also have a role?
Also, a detailed classification of the clinical spectrum of SARS‐CoV‐2
infection is given. Nevertheless, they do not mention how severe
asthmatics are decided in the study. I could not be sure that is it
classified according to the GINA or / other international guidelines. As
far as I understand from the manuscript, a confirmed diagnosis of severe
asthma seemed to be based on receiving therapy with one biological drug
(monotherapy or in addition to nonbiologic therapy). Moreover, the
authors, unfortunately, say that their ‘study design could appear as
inappropriate therapeutic management of patients with severe asthma and
SARS‐CoV‐2 infection’, according to the national guidelines. It is very
hard to comprehend what exactly they mean.
Comorbidity of cystic fibrosis (71.45%) was detected in 15/21 of their
patients.1 This is a too-high ratio. Are their study
group real cystic fibrosis
patient groups rather than severe asthma patients? In normal
circumstances, severe asthma patients do not have as much high
comorbidity as cystic fibrosis. In the literature, poor outcomes (e.g.,
the risk for hospitalization or intubation) were also reported after
SARS‐ CoV‐2 infection in severe asthma patients on biologic therapy was
associated with one or more comorbidity. Interestingly, there are no
poor outcomes for such high comorbidity in their patients. How do the
authors explain this contradiction?
Also, as a reader and pediatric allergists, we need to know these severe
asthmatic patients’ other laboratory and clinical parameters such as the
use of inhaled corticosteroids as well as their type of asthma, e.g.
eosinophilic or not, including total IgE, skin prick tests, specific IgE
results. As mentioned in the article,1 type 2
inflammation is usually known to control the expression of
angiotensin-converting enzyme 2 (ACE2) receptor in human bronchial cells
and affects the COVID-19 outcome. In the table of the
article,1 it is shown that the number of users of
inhaled bronchodilators is 11/21 patients, and inhaled steroids is 9/21
patients. According to the international asthma guidelines (e.g. GINA,
ATS, etc.), how a patient uses a biological product without taking even
(high dose) inhaled corticosteroids?
As expected, treatment with biologics was not found to be associated
with an increased risk of SARS-CoV-2 infection as well as exacerbation
of asthma in their study group. However, a recent review of case reports
and original articles by Poddighe et al.5 showed that
the rate of contracting SARS-CoV-2 infection in mepolizumab patients was
more than in omalizumab. In this study, is there any difference in
omalizumab and mepolizumab patients contracting SARS-CoV-2 infection?
Additionally, in another study about biologicals, among the 26 patients
experiencing COVID-19 disease, most (16/26) had been receiving
mepolizumab. Mepolizumab patients were mainly less allergic but more
eosinopenic together with other risk
factors/comorbidities.2 Indeed, various cohorts showed
that non-allergic asthma patients had a greater risk of SARS-CoV-2 test
positivity than allergic asthma patients.6
Moreover, some studies indicate that high doses of inhaled
corticosteroids and the chronic use of oral corticosteroids might be
associated with a predisposition to COVID-19 and poor
outcomes.7 Is this one of the reasons that the authors
did not see any poor outcomes in their patients?
I think that if these points are delineated, this valuable article would
be more understandable and helpful to readers as well as to the
literature.
References 1. Manti S, Giallongo A, Pecora G, Parisi GF, Papale
M, Mulè E, Aloisio D, Rotolo N, Leonardi S. Safety of biologics in
severe asthmatic patients with SARS-CoV-2 infection: A prospective
study. Pediatr Pulmonol. 2023 Jan 2. doi: 10.1002/ppul.26298. Epub ahead
of print. PMID: 36593591. 2. Papaioannou AI, Fouka E, Tzanakis Ν,
Αntoniou K, Samitas Κ, Ζervas Ε, et al. SARS-CoV-2 infection in severe
asthma patients treated with biologics. J Allergy Clin Immunol Pract.
2022: S2213-2198(22)00611-0. doi: 10.1016/j.jaip.2022.05.041.
3. Eger K, Hashimoto S, Braunstahl GJ, Brinke AT, Patberg KW, Beukert A,
et al. Poor outcome of SARS-CoV-2 infection in patients with severe
asthma on biologic therapy. Respir Med. 2020;177:106287. doi:
10.1016/j.rmed.2020.106287. 4. Hanon S, Brusselle G, Deschampheleire M,
et al. COVID-19 and biologics in severe asthma: data from the Belgian
severe asthma registry. Eur Respir J. 2020;56:2002857. 5. Poddighe D,
Kovzel E. Impact of Anti-Type 2 Inflammation Biologic Therapy on
COVID-19 Clinical Course and Outcome. J Inflamm Res. 2021;14:6845-6853.
doi: 10.2147/JIR.S345665. 6. Yang JM, Koh HY, Moon SY, Yoo IK, Ha EK,
You S, et al. Allergic disorders and susceptibility to and severity of
COVID-19: a nationwide cohort study. J Allergy Clin Immunol.
2020;146(4):790–8. 7. Kong-Cardoso B, Ribeiro A, Aguiar R, Pité H,
Morais-Almeida M. Understanding and Managing Severe Asthma in the
Context of COVID-19. Immunotargets Ther. 2021; 10:419-430. doi:
10.2147/ITT.S342636.