Understanding the mechanisms related to COVID-19 severity. The role of anti-interferon antibodies
It is crucial to understand why some individuals develop a much more severe form of Covid-19 disease than others.
Identifying the mechanisms underlying the inauspicious outcome of the infection may help improve patients' clinical therapeutic management.
The high production of antibodies capable of neutralising certain modulators of the immune system, type I interferons (IFN- I), and thus impairing their biological/antiviral activity, would appear to be at the forefront in the development of the most severe forms of Covid-19.
That is demonstrated by two new studies, carried out by Guido Antonelli's research group from the Department of Molecular Medicine at Sapienza University of Rome, in collaboration with the Departments of Public Health and Infectious Diseases and Experimental Medicine, the Istituto Superiore di Sanità and Johns Hopkins University, recently published in the European Journal of Immunology and Clinical Immunology.
The two papers revealed that the functionality of the IFN-I response, in particular the IFN-α and IFN-ω subtypes, is significantly reduced in patients who developed neutralising antibodies.
These are predominantly male patients hospitalised for severe forms of COVID-19, admitted to intensive care and with an inauspicious infection outcome. The researchers found that HIV-1 patients who develop severe forms of COVID-19 also have high concentrations of neutralising antibodies with a broad spectrum of specificity towards IFN-α and IFN-ω subtypes.
It was also observed that anti-IFN-I autoantibodies are associated with higher levels of markers of inflammation and specific haematological markers (such as neutrophils and platelets) and can be detected not only in blood samples but also in respiratory samples.
'A strength of our research,' says Guido Antonelli, 'is that we have carried out an analysis of the presence of neutralising antibodies on a large number of patients hospitalised for COVID-19. In all of them, a detailed assessment of the antibody specificity and the influence of these autoantibodies on the interferon-mediated response and the biochemical and haematological parameters associated with an increased risk of severe COVID-19 was carried out'.
'These studies,' says Carolina Scagnolari and Alessandra Pierangeli, research coordinators with the John Hopkins in Baltimore, add new elements to our understanding of the immunopathogenic mechanisms associated with infection caused by the new Coronavirus. Indeed, detecting these antibodies in individuals infected with SARS-CoV-2,' the researchers conclude, 'could allow better therapeutic management of patients'.
Anti-IFN-α/-ω neutralizing antibodies from COVID-19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity - Federica Frasca, Mirko Scordio, Letizia Santinelli, Lucia Gabriele, Orietta Gandini, Anna Criniti, Alessandra Pierangeli, Antonio Angeloni, Claudio M. Mastroianni, Gabriella d'Ettorre, Raphael P. Viscidi, Guido Antonelli, Carolina Scagnolari - European Journal of Immunology (2022) https://doi.org/10.1002/eji.202249824
High frequency of neutralizing antibodies to type I Interferon in HIV-1 patients hospitalized for COVID-19 - Mirko Scordio, Federica Frasca, Letizia Santinelli, Leonardo Sorrentino, Alessandra Pierangeli, Ombretta Turriziani, Claudio M. Mastroianni, Guido Antonelli, Raphael P. Viscidi, Gabriella d’Ettorre, Carolina Scagnolari - Clinical Immunology (2022) https://doi.org/10.1016/j.clim.2022.109068
Department of Molecular Medicine