Imagine a previously unknown bug—new to our immune defenses—that suddenly emerged and rapidly spread all over the globe, causing the deaths of millions and an economic breakdown due to the interruption of work in virtually every 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 of developing 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 pandemic due to SARS-CoV-2 infection. While the world was dealing with so many deaths and the resulting political, economic, and psychological challenges, a multidisciplinary group of scientists led by Professor Antonio Giordano, M.D., Ph.D., Director of the Sbarro Institute for Cancer Research and Molecular Medicine, teamed up to discuss the situation and hypothesize strategies to counteract the deadly bug.

They started by checking whether the high number of COVID 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 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 were analyzed to determine their 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 molecules largely vary from person to person.

“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 always likely be individuals that can mount an effective immune response, while others might not, eventually succumbing to the disease,” says Rita Emilena Saladino, an expert in the Tissue Typing Unit of the Grand Metropolitan Hospital Reggio Calabria.

Saladino is part of a team that first published their findings on the HLA-COVID relationship in 2020 in the International Journal of Molecular Sciences. That study analyzed HLA data and COVID incidence in the Italian provinces, in collaboration with Pierpaolo Correale, Chief of the Medical Oncology Unit, Grand Metropolitan Hospital “Bianchi Melacrino Morelli” of Reggio Calabria and colleagues.

The paper identified HLA class I genes, HLA-C*01, and HLA-B*44, that seemed permissive to SARS-CoV-2 infection. It 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.

The team has now performed an updated analysis of the relationship between HLA and severe COVID using two years of additional data through 2022. They have published their findings in the Journal of Translational Medicine. In this new paper, Correale and colleagues further investigated the HLA-COVID incidence association during the subsequent pandemic waves and then performed a “case-control” study analyzing HLA genotypes of patients hospitalized for COVID in two Italian regions, Campania and Calabria respectively.

The new study showed that the association of Human Leukocyte Antigen (HLA) genotype HLA-C*01 and HLA-B*44 with severe COVID risk varied and was eventually lost after the pandemic’s first waves, as could be expected considering the co-evolution of both the coronavirus and the immune response. But 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.

The study, including epidemiologists, pathologists, immunologists, and oncologists, 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.

“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 to the studies.

Provided by
Sbarro Health Research Organization (SHRO)