ROME (ITALPRESS) – Just imagine that a previously unknown microbe — new to our immune defenses — suddenly emerges and spreads rapidly around the world, causing the deaths of millions of people as well as a total economic collapse due to the suspension of most work activities virtually everywhere.Imagine, however, that the scientific community develops a powerful vaccine against the tiny microorganism in record time. How would you go about choosing who should be vaccinated first? To figure out who is at high risk of developing the severe form of the deadly disease? To figure out who should be protected with higher priority? If the story sounds familiar, that is exactly what happened with the recent COVID-19 pandemic due to SARS-CoV-2 infection. As the deaths were rising so fast they couldn’t be buried, and the whole world collapsed amid all sorts of political, economic and psychological problems, a multidisciplinary group of scientists, led by Professor Antonio Giordano, director of the Sbarro Institute for Cancer Research and Molecular Medicine, composed of epidemiologists, pathologists, immunologists and oncologists, came together to discuss the situation and hypothesize strategies to counter the deadly microorganism. The researchers began to investigate whether the high number of hospitalizations for COVID-19 in some Italian provinces could be associated with specific genetic determinants of the resident population. They conducted an ecological study, led by Giovanni Baglio of AGENAS (National Agency for Regional Health Services), using hospitalization data for COVID-19 from the Department of Civil Defense and genetic data from the largest local registry available: the Italian Bone Marrow Donor Registry. Donor samples are normally analyzed (typed) to determine the Human Leukocyte Antigen (HLA) genotype and verify tissue compatibility. HLA molecules, also known as Major Histocompatibility Complex (MHC), are those that can be recognized as foreign (non-self) by the recipient in the case of organ transplantation and result in organ rejection in the absence of adequate compatibility. In fact, HLAs are extremely diverse among individuals. “The reason for this diversity is that the role of HLA/MHC is to present microbial proteins to our immune system to trigger a powerful specific response against the microorganism to which these proteins belong. From an evolutionary point of view, this means that within the population there will be individuals able to mount an effective immune response, while others will eventually succumb to the disease,” says Rita Emilena Saladino, an expert at the Tissue Typing Unit of the Great Metropolitan Hospital of Reggio Calabria.By simply associating HLA data and the incidence of COVID-19 in Italian provinces, Pierpaolo Correale, head of the Medical Oncology Unit at the Ospedale Grande Metropolitano ‘Bianchi Melacrino Morellì in Reggio Calabria, and colleagues identified the HLA class I genes, HLA-C01 and HLA-B44, as permissive to SARS-CoV-2 infection. The ecologically based study was published in the International Journal of Molecular Sciences in 2020 and was the first to show the potential of such an inexpensive and rapid method to identify at-risk individuals, despite the inherent limitations of the ecological approach (HLA-B44 and C01 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 studied the association between HLA and the incidence of COVID-19 during successive pandemic waves and then conducted a “case-control” study by analyzing the HLA genotypes of patients hospitalized for COVID-19 in two Italian regions, Campania and Calabria, respectively. The study was made possible through collaboration with Roberto Parrella, head of the Respiratory Infectious Diseases Unit, and his team at the “Azienda Ospedaliera Specialistica dei Colli” in Naples.The results, published March 10, 2025 in the Journal of Translational Medicine (Correale, P., Baglio, G., Parrella, R. et al. A rapid ecologic analysis, confirmed by a case-control study, identifies class I HLA alleles correlated to the risk of COVID-19. J Transl Med 23, 303 https://doi.org/10.1186/s12967-025-06285-w, Springer Nature), showed that the association between HLA-C01 and HLA-B44 with the risk of severe COVID-19 varied and eventually disappeared after the first pandemic wave, as might be expected considering the co-evolution of both the coronavirus and the immune response. In contrast, expression of the HLA-B*49 allele emerged as a protective factor and was confirmed by the subsequent case-control study in Campania and Calabria. “Our studies suggest that the ecological approach, based on publicly available data, can be used in emergencies as a rapid and cost-effective way to determine priorities in patient management and during vaccination campaigns,” says Francesca Pentimalli, Professor of Pathology at LUM University of Bari and Adjunct Professor at the Sbarro Institute, Temple University.-photo Ipa Agency -(ITALPRESS).
