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).

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19–recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike–specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19–recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19–recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19–recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.

The characterization of cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 is fundamental to understand COVID‐19 progression and the development of immunological memory to the virus. In this study, we detected T‐cells reactive to SARS‐CoV‐2 proteins M, S, and N, as well as serum virus‐specific IgM, IgA, IgG, in nearly all SARS‐CoV‐2 infected individuals, but not in healthy donors. Virus‐reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immune‐checkpoint molecules PD1 and TIGIT. Of note, we detected antigen‐specific adaptive immune response both in asymptomatic and symptomatic SARS‐CoV‐2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell‐mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life‐threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and significantly impacts patients’ lives, particularly in its severe forms. AD clinical presentation varies over the course of the disease, throughout different age groups, and across ethnicities. AD is characterized by a spectrum of clinical phenotypes as well as endotypes. Starting from the current description of AD pathogenesis, this review explores the rationale of approved AD therapies from emollients to biologicals and introduces novel promising drugs.