INTRODUCTION
One of the most impressive aspects of SARS-CoV-2 infection is the broad
spectrum of consequences that may vary from a complete absence of
symptoms (asymptomatic infection) to a mild upper airways disease to
pneumonia whose severity may range from benign to fatal (1). The most
severe complication of the infection by SARS-CoV-2 is the acute
respiratory distress syndrome (ARDS) which may lead to mechanical
ventilation and ICU admission and is often fatal. The most frequent sign
of evolution towards respiratory failure or ARDS is dyspnea associated
with decreased oxygenation. The median time from the onset of symptoms
to dyspnea is 8 days (2), and the unfavorable evolution occurs about
10-15 days after the onset the first signs and symptoms of the infection
(3).
Since SARS-CoV-2 is a new virus, the first-line early defense against it
is the innate immunity, before the adaptive response occurs. Innate
immunity is based on both humoral and cellular elements, including
Natural Killer cells and gamma/delta T cells that kill infected cells,
thus limiting viral invasion, and secrete cytokines that cause
inflammation and stimulate the adaptive immune response. Most severe
cases of Covid-19, frequently leading to the death of affected patients,
are characterized by the activation of two major biological cascades:
the so-called “IL-6 cytokine storm” and a disseminated intravascular
cascade in the lung. The mechanisms leading to these events are still
incompletely defined, but their coincidence with the rise of the
adaptive response suggests that the immune response per se, particularly
the adaptive one, may play a role. In effect, Covid-19 patients with
agammaglobulinemia recovered without experiencing lung complications
(4). Thus, the type of immune response rather than the virus itself
seems to lead to the inflammatory events observed in the most severe
Covid-19 cases.
Atopic status is the genetic predisposition to produce a Type 2 immune
response to environmental antigens that are harmless for non-atopic
subjects. Type 2 immunity is characterized by the differentiation of
naïve T CD4+ cells towards Th2 effector cells, which is followed by IgE
production, eosinophilia, and mast cell activation. Type 2 immune
response relies on some keystone cytokines, including interleukin (IL)
4, IL-5, IL-9, and IL-13 (5, 6). IL-4 induces the differentiation of
naïve Th0 cells to Th2 cells, which in turn induce the isotype switching
to IgE production. In infection, the Th2 immune response counteracts the
microbicidal Th1 response, which could limit the tissue damage induced
by Th1-mediated inflammation (7). In a study on experimental Coronavirus
229E infection of the upper airways carried out in healthy volunteers,
atopy appeared to be associated with a more severe rhinitis score,
suggesting a less efficient anti-virus response (8). Another recent,
important finding is the reduced expression of ACE2, the SARS-CoV-2
receptor, in atopic subjects, which could be associated with reduced
susceptibility to the virus (9).
Since it seems that the immune response itself, rather than the virus,
leads to those catastrophic inflammatory events occurring in the most
severe Covid-19 cases, we hypothesized that atopic subjects infected by
SARS-CoV-2 might have a milder clinical course than non-atopic subjects,
and tested this hypothesis in a large cohort of hospitalized Covid-19
patients.