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Back COVID-19: a study by ISS confirms the protective role of type I interferons and compares the features of immune cells producing these factors in severe and asymptomatic COVID-19 patients


Type I Interferon (IFN) released by plasmacytoid dendritic cells (pDC) during the early phases of COVID1-9 infection plays a key role in stimulating the innate immune response and, in turn, in preventing the progression of the disease. A new study was conducted by a research team composed by researchers from San Raffaele University in Milan, Policlinico Tor Vergata Hospital, University of Padova, Metabolic Fitness Association and coordinated by Istituto Superiore di Sanità (ISS). The study outlined the importance of the innate immune response in controlling COVID-19 pathogenesis in a study published on Plos Pathogens

“We have studied the early interaction between SARS-CoV-2 and the immune cells in an in vitro model based on human peripheral blood cells (PBMC) - said Eliana Coccia from ISS, who coordinated the research - and we noticed that, even in the absence of a productive viral replication, SARS-CoV-2 stimulates the production of the antiviral type I and III IFN and the release of pro-inflammatory cytokines and chemokines, known to contribute to the cytokine storm associated to severe COVID-19 manifestation. Interestingly, type I IFN released from pDC is able to stimulate an antiviral response in the infected epithelial cells”.    

Moving from these data, the researchers characterized ex vivo the pDC phenotype and the balance between anti-viral and pro-inflammatory cytokines of COVID-19 patients stratified according to disease severity.  

“In particular - Nicola Clementi from UniSR explained - in asymptomatic SARS-CoV-2 infected subjects pDC were well-represented in the blood, expressed on their surface PD-L1 molecule and released type I IFN, thus leading to the induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum.” 

“Our study - the authors concluded - confirms the crucial and protective role of pDC/type I IFN axis in COVID-19, whose deeper understanding may contribute to the development of novel pharmacological strategies and/or host-directed therapies aimed at boosting pDC response since the early phases of SARS-CoV-2 infection”.  

The results of this research were obtained thanks to the productive and intensive collaboration between researchers and clinicians listed here below:  

Department of Infectious Diseases, Istituto Superiore di Sanità (Rome, Italy) 
Eliana M Coccia, Marilena P. Etna, Stefano Fiore, Daniela Ricci, Fabiana Rizzo, Martina Severa, Paola Stefanelli  

Infectious Disease Clinic, Policlinico Tor Vergata (Rome, Italy)  
Massimo Andreoni, Marco Iannetta, Alessandra Lodi  

Department of Molecular Medicine, University of Padova (Padua, Italy) 
Luisa Barzon, Alessandro Sinigaglia  

Laboratory of Medical Microbiology and Virology, Vita-Salute San Raffaele University (Milan, Italy) 
Massimo Clementi, Nicola Clementi, Elena Criscuolo, Roberta Diotti, Nicasio Mancini   

Metabolic Fitness Association (Monterotondo, Rome, Italy) 
Stefano Balducci