Study describes molecular difference between SARS-CoV-2 infections of different severity

An important study on SARS-CoV-2 was published in the journal CELL, from the collaboration between the laboratory of Microbiology and Virology of the Vita-Salute San Raffaele University and the Immunology Division of Boston Children's Hospital, Harvard Medical School.

Interferons are substances produced by cells in response to a wide variety of stimuli: the researchers described the molecular differences between SARS-CoV-2 infections with severe symptoms and with mild symptoms, identifying precisely a crucial element in the interferon response at the level of the upper airways.

High levels of antiviral response in the upper airways - less common in older patients - promote better control of the virus and put them at a reduced risk of serious complications.

The group of the UniSR Microbiology and Virology Laboratory, directed by Professor Massimo Clementi, was coordinated by Professor Nicasio Mancini, who shared the direction of the study with Professor Ivan Zanoni, immunologist of the Harvard Medical School.

If it is known that severe forms of COVID-19 are characterized by an overproduction of immune mediators, the role of interferons, in particular those of type III, still remained to be clarified and had given, in previous works, conflicting evidence.

Professor Nicasio Mancini, director of the UniSR Postgraduate School in Microbiology and Virology explains:

"The presence of the virus stimulates a response that acts not only as an alarm bell for more refined subsequent immune responses, but also for effective containment of the virus at this level. A less effective response, as observed in the older subjects we studied, can lead to greater involvement of the lower respiratory tract, where interferons, although present, are no longer able to control infection and the massive production of other mediators. inflammatory.

These data further highlight how interferons play opposite roles in different anatomical locations along the respiratory tract: efficient production in the upper airways can lead to faster elimination of the virus and to limit viral spread to the lower airways. However, when the virus escapes immune control in the upper tract, the abundant production of interferons in the lungs is not only unable to limit the virus more effectively, but contributes to the cytokine storm and tissue damage typical of patients with Serious COVID-19".

Professor Massimo Clementi adds:

"This work, provides an important molecular understanding of what is found in clinical practice with COVID-19 patients, i.e that young patients with high viral load effectively resolve symptoms without affecting the  lower respiratory tract. Crucially, it also suggests a fundamental role of non-specific immunity in the course of a viral disease, a concept that was unthinkable until a few years ago".