A weak immune response to two doses of vaccine against severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) has been observed in immunocompromised patients, includingsolid organ transplant recipients (SOTRs)1,2,3. Studies focused on third dose in SOTRsrevealed that the percentage of responders increased even if a large portion of patientsremained at risk for COVID-194. More in detail, the humoral response to three doses ofvaccine at 1 month after the third dose in SOTRs ranged from ≈50 to ≈70% ofpatients5,6,7. Therefore at least a third of the patients who have an impaired immuneresponse remain unprotected despite the administration of three doses of anti-SARS-CoV-2vaccine8,9. Similar data emerged from studies conducted on other categories ofimmunosuppressed patients: less than 40% of onco-haematological patients developantibodies after administration of two doses of vaccine and only a quarter ofnon-responders retrieve a humoral response after the third dose10,11. Likewise,rheumatological diseases induce a known frequent immune dysregulation that compromises anadequate response to the anti-SARS-CoV-2 vaccine12. Additionally, the emergence of thenew Omicron variant has posed new issues in terms of vaccine immunogenicity. It has beenobserved that three doses of vaccine lead to a lower neutralization response againstOmicron variant than respect to the other variants (Delta, Wild type), especially intransplanted patients13. The use of monoclonal antibodies in prophylaxis may represent avaluable choice for non-responder subjects after complete vaccination in order to preventsevere COVID-19. In this regard, recent data showed that the long-acting monoclonalantibodies (LAABs) were able to block the binding of the SARS-CoV-2 virus to host cellsand protect against infection in cell and animal models of disease14. Evusheld (AZD7442)is a combination of two LAABs- Tixagevimab and Cilgavimab- derived from B-cells donatedby convalescent patients after SARS-CoV-2 virus. These human monoclonal antibodies wereoptimized with half-life extension and reduced Fc receptor and complement C1q binding.The half-life extension more than triples the durability of its action compared toconventional antibodies and could afford up to 12 months of protection from COVID-19following a single administration15,16. The reduced Fc receptor binding aims to minimizethe risk of antibody-dependent enhancement of disease - a phenomenon in whichvirus-specific antibodies promote, rather than inhibit, infection or disease. Data on thesafety and efficacy of Evusheld administered in the context of pre-exposure prophylaxisof Covid-19 can be obtained from the Provent trial that represents the largest study todate conducted in the world setting. PROVENT is a Phase III, randomized, double-blind,placebo-controlled, multi-center trial assessing the efficacy and safety of a single300mg dose of AZD7442 compared to placebo for the prevention of COVID-19. The trial wasconducted in 87 sites in the US, UK, Spain, France and Belgium. 5.197 participants wererandomized in a 2:1 ratio to receive a single intramuscular (IM) dose of either 300mg ofAZD7442 (n = 3460) or saline placebo (n = 1,737), administered in two separate,sequential IM injections. More than 75% had baseline co-morbidities and othercharacteristics that are associated with an increased risk for severe COVID-19 shouldthey become infected, including those with immunosuppressive disease or takingimmunosuppressive medications. In the Phase III PROVENT trial, Evusheld seems to reducethe risk of developing symptomatic COVID-19 by 77%, (95% confidence interval (CI): 46,90) compared to placebo with high neutralizing antibody titers for at least six months,although further studies will be needed (AstraZeneca news release. New analyses of twoAZD7442 COVID-19 trials in high-risk populations confirm robust efficacy and long-termprevention17. There were no cases of severe COVID-19 or COVID-19-related deaths in thosetreated with AZD7442. In the placebo arm, there were three cases of severe COVID-19,which included two deaths. The monoclonal antibodies were well-tolerated and preliminaryanalyses show adverse events were balanced between the placebo and AZD7442 groups18.Other ongoing trials include Storm Chaser and Tackle COVID-19; although they are focusedon the post-exposure prevention of severe COVID-19 in subjects already exposed to theviral agent, they confirm the safety and tolerability profile of Evusheld in accordancewith what emerged from the Provent trial. In Italy, following the publication of AIFAdetermination N. 42 of 19.02.2022, starting from 20.02.2022 it is possible to use thecombination of Evusheld monoclonal antibodies (Tixagevimab-Cilgavimab) in specific anddefined categories of patients who have severe immune system impairment including solidorgan transplant recipients. In light of the encouraging data currently available,Evusheld could