The team, which includes epidemiologists, pathologists, immunologists, and oncologists, has developed a statistical method to identify which patients are at higher risk or, conversely, more protected from severe forms of the disease.
This innovative approach is based on the study of Human Leukocyte Antigen (HLA) molecules, which are known for their role in transplant rejection. By analyzing these molecules, the researchers have uncovered patterns that can predict an individual’s susceptibility to COVID-19 or their potential resilience against it.
This discovery could pave the way for more targeted prevention strategies and personalized treatment plans. “Prevention and the identification of high-risk patients will always remain a priority for our Research Institute,” stated Giordano. The findings not only enhance our understanding of the disease but also provide a valuable tool for prioritizing care and resources during future health crises.
This breakthrough represents a significant step forward in the global effort to combat COVID-19.
Scientists find a rapid tool to identify patients at high risk of severe COVID-19Imagine that a previously unknown bug – new to our immune defences – suddenly emerges and rapidly spreads all over the globe causing the death of million people and an economic breakdown due to the stop of most working activities in virtually any country.
Imagine, however, that the scientific community develops in record time a powerful vaccine against the tiny bug. How would you pick who should be vaccinated first? Who is at high risk to develop the severe form of the deadly disease? Who is to be protected with higher priority?
Well, if you find the story familiar, this is what recently happened with the COVID-19 pandemics due to SARS-CoV-2 infection. The whole world was collapsing dealing with so many deaths that couldn’t even be buried in a decent time and all sorts of political, economic, psychological troubles.
In the meanwhile, a multidisciplinary group of scientists led by Professor Antonio Giordano Director of the Sbarro Institute for Cancer Research and Molecular Medicine, including epidemiologists, pathologists, immunologists, and oncologists, teamed up to discuss the situation and hypothesize strategies to counteract the deadly bug.
They started checking whether the high number of COVID-19 hospitalizations in certain Italian provinces could be associated with specific genetic determinants of the resident population.
They performed a so called ‘ecological study’, led by Giovanni Baglio from the AGENAS (Italian National Agency for Regional Healthcare Services) using COVID-19 hospitalization data from the Italian Civil Protection Department and genetic data from the widest local repository available: the Italian Bone Marrow Donor Registry. The donor samples are analyzed to determine their Human Leucocyte Antigen (HLA) genotype and check possible tissue compatibility.
The HLA molecules, also called Major Histocompatibility Complex (MHC), are those that can be recognized as foreign (non-self) by the receiving individual upon organ transplantation and determine organ rejection in the absence of adequate compatibility. Indeed, HLA are highly different among individuals. “The reason for this diversity is that HLA/MHC role is to present microbial proteins to our immune system to unleash a powerful specific response against the bug to which these proteins belong.
From the evolutionary point of view it means that within the population there will be individuals that can mount an effective immune response, while other will eventually succumb to the disease.” Says Rita Emilena Saladino an expert of the Tissue Typing Unit of the Grand Metropolitan Hospital Reggio Calabria.By simply associating HLA data and COVID-19 incidence in the Italian provinces, Pierpaolo Correale, Chief of the Medical Oncology Unit, Grand Metropolitan Hospital ‘Bianchi Melacrino Morelli’ of Reggio Calabria and colleagues, identified HLA class I genes, HLA-C*01, and HLA-B*44, that seemed permissive to SARS-CoV-2 infection.
The study was published in 2020 on the International Journal of Molecular Sciences and was the first to show the potential of such an economic and rapid way to identify individuals at risk, despite the limits of the ecological approach (HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across Italy.
Correale P, Mutti L, Pentimalli F, Baglio G, Saladino RE, Sileri P, Giordano A.Int J Mol Sci. 2020 Jul 23;21(15):5205. doi: 10.3390/ijms21155205.PMID: 32717807).
To confirm the analysis, Correale and colleagues further investigated the HLA-COVID-19 incidence association during the subsequent pandemic waves and then performed a ‘case-control’ study analyzing HLA genotypes of patients hospitalized for COVID-19 in two Italian regions, Campania and Calabria respectively.
The study was possible thanks to the collaboration with Roberto Parrella, Chief of the Respiratory Infectious Diseases Unit, and his team from the “Azienda Ospedaliera Specialistica dei Colli”, Napoli.
The results, published on the Journal of Translational Medicine (Springer Nature) showed that the association of HLA-C*01 and HLA-B*44 with severe COVID-19 risk varied and was eventually lost after the first pandemics waves, as could be expected considering the co-evolution of both the coronavirus and the immune response.
On the contrary, the expression of HLA-B*49 allele emerged as a protective factor and was confirmed by the following case-control study in Campania and Calabria.
“Our studies suggest that the ecologic approach, based on publicly available data, can be used in emergency as a rapid and inexpensive method to determine priorities in patient management and during vaccination campaigns.” states Francesca Pentimalli, Professor of Pathology at LUM University, Bari and Adjunct Professor at the Sbarro Institute, Temple University, contributor of the studies.
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