Reply to Morais-Almeida.
To the Editor,
We appreciate Dr. Morais-Almeida’s comments 1 about
our Letter to the Editor, presenting additional literature about asthma
prevalence in severe COVID-19 patients and highlighting data that
contrasts our hypothesis that asthma, particularly type 2 asthma, may be
protective against severe disease.
The data that protection may be dependent on type 2 immunity is derived
from the higher percentage of asthmatics being atopic2, also reflected in the series of
~2,500 patients regularly followed up in our Allergy
Unit. Yu et al. 3 provided preliminary evidence about
this in a single-center retrospective study, where COVID-19 atopic
patients had less severe infections, milder lung damage compared to age-
and gender- matched COVID-19 controls.
ACE-2, the SARS-CoV-2 receptor, is linked to type 1 and 2 interferon
signatures, and found to be overexpressed in type 2-low asthmatics4. Nevertheless, different outcomes in distinct asthma
phenotypes still need to be addressed in COVID-19 studies.
Besides Italy and China, reports from Russia 5 on
~1,300 intensive care unit patients with SARS-CoV-2
infection confirm the observation of a low prevalence of chronic lung
diseases (i.e. asthma as well as COPD).
Although preliminary data on the first COVID-19 cases in the US6 seem to contrast these observations, the higher
prevalence of asthma in US COVID-19 hospitalised patients should be
considered alongside a higher overall prevalence in these countries
compared to Europe and China, as well as on the influence of other
comorbidities (i.e. obesity) and host factors (i.e. age, race: 33% were
non-Hispanic black patients in the study by Garg et al.) impacting
COVID-19 outcomes. Another report from Sweden 7highlights the association between severe asthma and severe COVID-19.
The severe asthma phenotype is often characterized by mixed granulocytic
populations (neutrophilic and eosinophilic), prevalent type 1
inflammation, increased IFN-γ levels in the airways and ineffectiveness
of ICS. This severe phenotype by itself, although accounting for less
than 5% of asthmatic patients, would justify the CDC (and other
institutions) including asthma as a risk factor for COVID-19. Data from
the UK 8, apart from confirming the role of additional
comorbidities, draw attention to the recent use of oral steroids, which,
indeed, may be a clue for uncontrolled and/or severe asthma.
Uncontrolled asthma is a risk factor for viral exacerbations and
hospitalizations and we embrace the opportunity to stress the importance
of optimal adherence to asthma controlling medications, regular
follow-up and specialist-assessment of disease activity. Moreover,
treatable comorbidities, which may impair asthma control, should always
be managed. Promoting vaccination for preventable respiratory infections
(i.e. Influenza and Pneumococcal pneumonia) is also advisable. Future
studies may help better distinguishing the impact of different asthma
phenotypes and comorbidities on COVID-19 outcome.
Carli G.1, Cecchi L.1, Stebbing
J.2, Parronchi P.3, Farsi
A.1
1 SOS Allergy and Clinical Immunology, USL Toscana
Centro, Prato Italy
2 Department of Surgery and Cancer, Imperial College
London, London SW7 2AZ, UK
3 Department of Experimental and Clinical Medicine,
University of Florence, Florence, Italy