The COVID-19 pandemic highlighted the complexity of the immune system and its response against emerging pathogens. In fact, the immune response to COVID-19 is a field of research that is still alive and one of the unknowns that remain open is related to the variability in the severity of the disease presented by vaccinated individuals. Despite the success of vaccines, which were key to controlling the crisis by preventing the most severe forms of the disease, it has been seen that some vaccinated individuals still suffered severe forms.
The reason for this phenomenon is what has been evaluated in the study by Dr. Arnau Antolí, carried out in collaboration between the Hereditary Cancer group of IDIBELL and the ICO, led by Dr. Conxi Lázaro, and the Systemic, Vascular Diseases and Aging group of IDIBELL and the Bellvitge University Hospital, which has Dr. Xavier Solanich as principal investigator, in a research project that has received financial support from the 2020 La Marató de 3Cat Foundation dedicated to Covid-19.
Interferon I neutralizing autoantibodies, a risk factor for severe COVID-19
The study, recently published in Clinical Immunology, has focused on a possible key factor that could explain this vulnerability: type I interferón neutralizing antibodies. These autoantibodies have previously been linked to COVID-19 severity in unvaccinated individuals, but their role in vaccinated individuals has not yet been studied.
To analyse it, clinical and laboratory data were collected from 670 vaccinated patients who were admitted to Bellvitge Hospital for pneumonia derived from COVID-19 between April 2021 and December 2022. Of these, 13.7% (92) had IFN-I neutralizing autoantibodies, of which 38% (35) were able to block IFN-I in vitro. Patients with these neutralizing autoantibodies developed significantly more severe pneumonia. In other words, patients with IFN-I neutralizing autoantibodies were shown to be more likely to develop severe pneumonia despite having had an adequate response to the vaccine. However, they have also found that the vaccine helped to attenuate this predisposition: in vaccinated patients, the presence of these autoantibodies increased the risk of suffering critical pneumonia by 2.3 times, a relatively low figure compared to unvaccinated patients, where the risk is multiplied by 17 if the patient has these autoantibodies.
Despite vaccination, the risk persists but is lower
In view of the results and according to the researchers, it is clear that IFN-I neutralizing autoantibodies play a key role in the immune response to COVID-19, both in vaccinated and unvaccinated patients. In fact, they are an independent risk factor: having these antibodies carries an added risk, just as old age, obesity, or being immunosuppressed do. The risk is lower than in the unvaccinated, but it persists.
This implies that the detection of autoantibodies that block IFN-I can help distinguish individuals at increased risk of severe viral infections, allowing early antiviral treatment to be started or stricter preventive vaccination recommendations to be followed. It remains to be seen how this new information can be translated into routine clinical practice.
The Bellvitge Biomedical Research Institute (IDIBELL) is a research center established in 2004 specialized in cancer, neuroscience, translational medicine, and regenerative medicine. It counts on a team of more than 1.500 professionals who, from 73 research groups, publish more than 1.400 scientific articles per year. IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona, and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).