DISCUSSION
Several clinical observations demonstrate that the severity of SARS-CoV2
infection may range from asymptomatic to a respiratory illness of
variable severity. One of the most serious complications is atypical
pneumonia. Critically ill, immunocompetent patients show an uncontrolled
secretion of pro-inflammatory cytokines (the so-called cytokine storm)
that plays a major role in determining lung injury and are responsible
for the high mortality rate. Thus, in severe cases, the virus induces a
marked dysregulation of the immune response, which, notably, occurs in
immunocompetent individuals. Hyper-expressed cytokines include
IFN-gamma, TNF-alpha, and IL-6, which are responsible for symptoms and
signs such as fever, fatigue, flu-like symptoms, vascular leakage due to
endothelial dysfunction, cardiomyopathy, hypotension, lung injury,
activation of the coagulation cascade, and diffuse intravascular
coagulation (12-17). The cytokine storm leads to the rapid proliferation
and activation of T cells, macrophages, and natural killer cells that
eventually secrete > 150 inflammatory cytokines,
chemokines, and chemical mediators (18,19). The cytokine storm does not
occur in patients with uncomplicated SARS-CoV-2 infection (2,20).
Atopic patients are genetically predisposed to mount Th2 type
immune-mediated responses; these responses do not imply the expression
of the main cytokines involved in the SARS but rather of IL-4, IL-5, and
IL-13. Further, a recent study observed a lower expression of the ACE-2
receptor among allergic subjects (9). On this basis, we hypothesized
that allergic patients might be both less prone to SARS-CoV-2 infection
and/or might have a less severe SARS-CoV-2 infection than non-atopic
individuals. To test these two hypotheses, a large epidemiological study
on a representative sample including both infected and non-infected
subjects considering atopic status as a variable would be required. In
the impossibility to carry out such a field epidemiological study, we
tried to address the second hypothesis focusing on more than 500
patients with confirmed Covid-19 infection severe enough to warrant
hospital admission. Thus, our study population lacks both asymptomatic
and symptomatic SARS-CoV-2 infected patients with very mild disease, as
these patients had to spend their quarantine period at home. Despite
these obvious limitations, our study demonstrates that among
hospitalized patients with severe Covid-19, atopic patients have less
severe disease. Notably, the “protective” effect of atopic status did
not depend on the age or sex of patients nor the presence of other
co-factors, such as cigarette smoke, coronary heart disease, diabetes,
thrombosis, or hypertension. We are not in the position to ascertain
whether the immunological scenario that we have hypothesized and that
prompted us to perform this study is correct, as this would require an
immune-histochemical analysis of patients’ sputum. Nonetheless, our
clinical findings make our initial hypothesis believable suggesting that
the genetic predisposition to a Th2-oriented immune response might help
to avoid the cytokine storm.
In conclusion, atopic status seems to protect against the most severe,
often fatal consequences of SARS-CoV-2 infection. Such finding may be of
help for future studies investigating how to limit the clinical
consequences of this infection.
CONFLICT OF INTEREST: No author has conflicts of interest to declare.
FUNDING: no funding.
AUTHORS CONTRIBUTIONS: RA and ES conceived the study. RA coordinated the
study and wrote the manuscript. AT, GM, BY, PB, AM, MG, AS, and FS cared
for Covid-19 patients and provided the clinical data. DA performed the
statistical analysis.
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Table 1: Demographic and clinical features of the study population. The
multiple logistic regression analysis including age, sex, smoking, and
all the comorbidities, shows a significant association between
non-atopic status and a significantly higher risk of having severe
COVID-19-related pneumonia.