<div><i>Corresponding author:</i></div><div>Professor Dr. med. L. Klimek</div><div>Center for Rhinology and Allergology</div><div>An den Quellen 10</div><div>D-65183 Wiesbaden</div><div>Tel.: 0049-611 – 308 6080</div><div>Ludger.Klimek@Allergiezentrum.org</div><div>To the Editor,</div><div>Following our early report in Allergy [1], there was several studies
published in the same direction showing the benefit of continuation of
inhaled steroids in COVID-19. Inhaled budesonide represents a standard
of care for patients with asthma, allergic rhinitis and chronic
rhinosinusitis [1-3]. It is recommended that in COVID-19, patients
with chronic inflammatory airway diseases should continue
guideline-based pharmacological treatment including ICS and/or
biological therapies [1, 2]. New data indicate that patients with
various asthma endotypes may show a different risk profile for
SARS-CoV-2 infection and a different course of COVID-19. Patients
suffering from allergic asthma (type 2 inflammation) seem to have a
lower risk of developing COVID-19 than patients with non-type 2 asthma
[4].</div><div>Ramakrishnan et al. performed an open-label, parallel-group, randomized
controlled trial to compare standard of care with the additive use of
inhaled budesonide [5]. The authors claim that this is an easily
accessible and effective intervention in early COVID-19. Their data also
suggest a potential benefit in the prevention of long COVID-19.</div><div>However, these statements may not be sufficiently proven. This was an
open study, in which patients and staff were aware of the therapy used.<i>Placebo</i> effects, for
example for inhalant asthma drugs, can be observed in 21 to 46% of
cases, especially for subjective outcomes [6]. Effects assessed
during this study, including the primary endpoint (COVID-19-related
urgent care visit, including emergency department visits or
hospitalization), may all be influenced by the subjective perception of
the patients and their treating physicians. Secondary endpoints,
including objective measures like blood oxygen saturation and SARS-CoV-2
load, were not different between the groups. The study population was
small, including 146 participants of which 73 were randomized to usual
care and 73 to the budesonide group. A cautious interpretation of these
data is warranted, since an updated interim analysis from a larger
phase-III study, including 2,617 people with risk factors for adverse
outcomes with COVID-19, did not show such favorable results [7].
Inhaled budesonide reduced the time to self-reported recovery by a
median of 3 days. However, it did not meet the primary outcome parameter
(COVID-19 hospitalizations/deaths) even though these rates were lower in
the budesonide versus the usual care group (59/692 (8.5%) and 100/968
(10.3%) respectively) [7].</div><div>Ramakrishnan et al. hypothesized that an early administration of inhaled
budesonide is beneficial at the early stage of COVID-19. Importantly,
this would suggest a low-cost and safe therapy. However, based on the
evidence from this and other studies, more research is still necessary
to support this recommendation.</div><div>Literatur</div><div>1. Bousquet J, Akdis C, Jutel M et al. Intranasal corticosteroids in
allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI
statement. Allergy 2020; 2020 Mar 31. Online ahead of print. PMID:
32233040. doi:10.1111/all.14302 doi 343917 de-38m</div><div>2. Bousquet J, Jutel M, Akdis CA et al. ARIA-EAACI statement on asthma
and COVID-19 (June 2, 2020). Allergy 2020; 76: 689-697.
doi:10.1111/all.14471 doi</div><div>343917 de-38m</div><div>3. Klimek L, Jutel M, Bousquet J et al. Management of patients with
chronic rhinosinusitis during the COVID-19 pandemic-An EAACI position
paper. Allergy 2021; 76: 677-688. doi:10.1111/all.14629</div><div>4. Skevaki C, Karsonova A, Karaulov A et al. Asthma-associated risk for
COVID-19 development. The Journal of allergy and clinical immunology
2020; 146: 1295-1301. doi:10.1016/j.jaci.2020.09.017 doi</div><div>37848 de-38m</div><div>5. Ramakrishnan S, Nicolau DV, Langford B et al. Inhaled budesonide in
the treatment of early COVID-19 (STOIC): a phase 2, open-label,
randomised controlled trial. The Lancet Respiratory medicine 2021.
doi:10.1016/S2213-2600(21)00160-0 doi</div><div>938190 de-38m. doi:10.1016/S2213-2600(21)00160-0 doi</div><div>938190 de-38m</div><div>6. Dutile S, Kaptchuk TJ, Wechsler ME. The placebo effect in asthma.
Current allergy and asthma reports 2014; 14: 456.
doi:10.1007/s11882-014-0456-2 doi</div><div>501311 de-38m</div><div>7. Yu L-M, Bafadhel M, Dorward J et al. Inhaled budesonide for COVID-19
in people at higher risk of adverse outcomes in the community: interim
analyses from the PRINCIPLE trial: Cold Spring Harbor Laboratory Press;
2021. doi:10.1101/2021.04.10.21254672 doi</div>