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.