Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

Over the past year and a half, SARS-CoV-2, the etiological agent of the COVID-19 pandemic, led to a total of almost 200 million cases, causing more than 4 million of deaths globally (Johns Hopkins University, CSSE) [1]. While we are facing rising daily hospitalizations (https://ourworldindata.org/covid-hospitalizations, accessed on July 31, 2021) [2], attributable to novel emerging variants of the virus [3, 4], we also observe a decrease in both hospitalizations due to severe forms of the disease and deaths in several parts of the world, thanks to the launch of massive vaccination campaigns [2]. To date, 4 billion vaccine doses have been administered [1]. Despite of the efforts of global organizations to face this health emergency, including the COVAX plan which aims to achieve the vaccination coverage in developing countries [5], we are still far from reaching the desired results and the end of this pandemic especially in emerging countries. As we discussed in our recent review on “COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy” [6], vaccines represent one of the most valuable aid to halt the SARS-CoV-2 spread. The emergence of novel variants of concern (VOC) aroused concern among the scientific community, since they are associated with a rise of viral transmissibility [7], and with a reduction in the therapeutic response to both monoclonal antibodies and antibody activity in vaccinated individuals [8]. Nevertheless, results arising from the analysis of vaccine coverage against the emerging Delta variant are promising [9]. It is known that the mRNA vaccines, both BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), can potentially be implemented to match the need of a response against SARS-CoV-2 mutations. For this reason, it is crucial to increase the genomic surveillance in the different departments of public health systems all over the world [10]. In the same publication [6], we arrive at the conclusion that not only the virus, but significantly also the synergic relationship with the host represents the core of the understanding of mechanisms underpinning the infectious cycle, transmission, resistance and susceptibility to SARS-CoV-2. In addition, we also expressed concern about effects that environmental pollution may exert on susceptibility to SARS-CoV-2 by diminishing immune responses. We are aware that increased knowledge of this aspects is fundamental to unveil the clinical course and a more targeted therapeutical approach for patients affected by COVID-19. In this editorial, we focus on genetic and genomics susceptibility factors to COVID-19, and we aim to summarize the current knowledge in the literature providing an updated, easy to consult and constantly revised tool, through an update of Table 2 from our recent review [6].