COVID-19 prophylaxis in immunosuppressed patients: Beyond vaccination
Authors: Ivan Gentile, Nicola Schiano Moriello
Journal: PLoS Medicine (2022)

Since early 2020, the Coronavirus Disease 2019 (COVIDAU : PleasenotethatCOVID À 19hasbeendefine-19) pandemic has caused hundreds of millions of cases and several million deaths worldwide [1].The development of effective vaccination has substantially changed the course of the pandemic, and the introduction of mass vaccination policies in most high-and middle-income countries has drastically reduced the number of new cases, hospitalizations, and deaths.However, vaccination is not the only tool able to provide immune prophylaxis against COVID-19.Herein, we discuss the use of monoclonal antibodies in addition to vaccination in order to better protect vulnerable people, particularly those with immunosuppression. Reduced vaccine efficacy in immunocompromised patientsIn most high-income countries, 4 vaccines have been authorized for primary prophylaxis against COVID-19.These vaccines afforded up to 95% protection against the disease in clinical trials.However, their efficacy tends to decline over time [2].Moreover, COVID-19 vaccination was found to have suboptimal efficacy in immunocompromised patients, thus leaving a nonnegligible portion of these patients at risk of infection [3].In particular, patients undergoing treatment with rituximab are at high risk of not developing a serological response to COVID vaccination [4].Studies in Israel and the USA found that 40% and 44% of hospitalized vaccine-breakthrough cases, respectively, were immunocompromised patients [5,6].Notably, the proportion of immunosuppressed adults in the USA is estimated to be about 4% of the population, and this number is likely to increase due to greater life expectancy, improved medical management, and the introduction of new immunosuppressive treatments [7].Immunosuppression should be seen as a continuous spectrum of different conditions, with fully immunocompetent patientsAU : PerPLOSstyle; }subjects}shouldnotbeusedforhumanpatients:Henc at one extreme and patients with completely impaired immune function at the other, interspersed with several degrees of immunosuppression that can be associated with one or more exacerbating factors (for instance, advanced age, chronic diseases, and congenital immunodeficiencies).Moreover, the use of targeted immunosuppressive therapies has induced different conditions, in which one or more specific branches of the immune system are nonfunctional while the others are almost untouched.Some studies have shown that the strategy of administering a third dose of COVID-19 vaccine could benefit some groups of immunocompromised patients, such as recipients of solidorgan transplants or patients in hemodialysis [8].However, this strategy is not effective in all patients: For instance, patients with B cell lymphoproliferative disease in treatment with rituximab or ibrutinib seem to respond only partially to COVID-19 vaccine, even after a third dose [9].Therefore, several million people, although fully vaccinated with 3 doses, remain vulnerable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoVAU : PleasenotethatSARS À CoV -2) infection.