BACKGROUND. Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. METHODS. We performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes. RESULTS. Patients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8⁺ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4⁺ T and CD8⁺ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A–expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. CONCLUSION. The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms. FUNDING. This study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the “Excellence Departments 2018–2022 Project”) derived from Ministero dell’Istruzione, dell’Università e della Ricerca (Italy).

Monoclonal antibodies (mAbs) approved for use as add-on therapy in patients with severe asthma target the underlying pathogenesis of asthma. Omalizumab binds immunoglobulin E (IgE), thereby inhibiting its interaction with the high-affinity IgE receptor and reducing the quantity of free IgE available to trigger the allergic cascade. Anti-interleukin (IL)-5 mAbs mepolizumab, benralizumab and reslizumab block the interaction between IL-5 and its receptor on eosinophils, thus targeting the eosinophilic pathway in asthma. Most mAbs are available as intravenous (IV) or subcutaneous (SC) formulations, as their high molecular weight and gastric degradation preclude oral administration. This review compares the pharmacology, efficacy, immunogenicity, injection- and infusion-related adverse drug reactions of subcutaneously administered omalizumab and mepolizumab with the intravenously administered reslizumab. In terms of pharmacokinetics, IV route of administration appears to be superior to the SC route due to quicker absorption, greater bioavailability, shorter time to maximum serum concentration and similar elimination half-life. Route of administration does not appear to translate into striking differences in efficacy and safety of mAbs used for the treatment of severe asthma, as all are generally considered to be effective and well tolerated. Hypersensitivity and administration-related reactions have been described with both IV and SC mAbs. mABs are effective and have low immunogenicity due to their nature as humanised antibodies. Evidence on the use of mAbs in indications other than severe asthma suggest that both the SC and the IV routes of administrations have their respective advantages and disadvantages; but their full utility remains to be elucidated.

Severe asthma and rhinosinusitis represent frequent comorbidities, complicating the overall management of the disease. Both asthma and chronic rhinosinusitis (CRS) can be differentiated into endotypes: those with type 2 eosinophilic inflammation and those with a non-type 2 inflammation. A correct definition of phenotype/endotype for these diseases is crucial, taking into account the availability of novel biological therapies. Even though patients suffering from type 2 severe asthma—with or without CRS with nasal polyps—significantly benefit from treatment with biologics, the existence of different levels of patient response has been clearly demonstrated. In fact, in clinical practice, it is a common experience that patients reach a good clinical response for asthma symptoms, but not for CRS. At first glance, a reason for this could be that although asthma and CRS can coexist in the same patient, they can manifest with different degrees of severity; therefore, efficacy may not be equally achieved. Many questions regarding responders and nonresponders, predictors of response, and residual disease after blocking type 2 pathways are still unanswered. In this review, we discuss whether treatment with biological agents is equally effective in controlling both asthma and sinonasal symptoms in patients in which asthma and chronic rhinosinusitis with nasal polyps coexist.

Vultaggio A, et al. Allergy Asthma Immunol Res. 2020 Sep;12(5):885-893. https://doi.org/10.4168/aair.2020.12.5.885