LAUSR

Since the first case of COVID-19, at the end of 2019, SARS-CoV-2 has spread rapidly worlwide, causing the death of more than 5 million people to this date and profoundly impacting population lifestyles. Clinical manifestations of COVID-19 occur over a wide spectrum of severities, ranging from asymptomatic, mild, moderate, severe, and critical cases, which can be fatal. This enormous variability might be due to specific personal features, including the individual immune response, which can determine disease clinical course and outcome. Therefore, failures/defects of the immune system, as in primary immunodeficiencies, should present a greater potential risk for more severe forms of COVID-19. Primary immune deficiencies, currently called Inborn Errors of Immunity (IEI), are genetic disorders classically characterized by an increased susceptibility to infection caused by a disruption in the development or regulation of an immune pathway. X-Linked Agammaglobulinemia (XLA), a type of IEI also called Bruton’s agammaglobulinemia, is a rare immunodeficiency disorder characterized by absent/very low mature B lymphocytes in blood and tissues. XLA is caused by BTK gene mutations, which encode the Bruton or B-cell Tyrosine Kinase (BTK) protein, and play pivotal roles in pro-and pre-B cell maturation. BTK loss-of-function mutation interferes with B cell development resulting in very low (or absent) levels of serum and mucosal immunoglobulins and high susceptibility to extracellular bacterial, entero-, and respiratory virus’ infections. In contrast, T-cells are normal in number and functions, with no change in their proliferative responses to antigens. Previous reports have demonstrated that XLA patients are at risk for severe disease with SARS-CoV-2 infection. Authors have reported clinical symptoms with important increase in inflammatory markers , associated with long viral persistence, suggesting a role for antibodies in reduction of viral load. Ponsford et al. (2021) observed that XLA patients remain susceptible to severe disease. Persistent infection is common and is likely to carry a significant risk of novel variant evolution. Vaccination is a safe and effective tool to induce a protective immune response in immunocompetent individuals. Immunocompromised patients, in turn, have an increased susceptibility to vaccine-preventable infections, emphasizing the importance of vaccination in this group whenever possible. Although in some IEI conditions, as in XLA, low or absent antibody response to vaccines is observed, vaccination may induce other protective immune mechanisms, such as the cellular immune response. Thus, the immune status of vaccinated immunodeficient individuals is crucial. Currently, multiple anti-COVID-19 World Health Organization (WHO) approved vaccines are being used worldwide. These vaccines are either mRNA, replication-deficient vector, inactivated whole virus, or protein-based vaccine. The European Society for Primary Immune Deficiency (ESID) recommends that IEI patients receive COVID-19