Cracking the code of a correlate of protection against SARS-CoV-2 breakthrough infection in cancer patients

The level of protection against SARS-CoV-2 breakthrough infections conferred by the presence of anti-S1 SARS-CoV-2 antibodies (IgGs) in cancer patients is still understudied. This work examines the existence of an anti-S1 immunoglobulin G (IgG) -based correlate of protection (CoP) established by prospectively collected observational data about breakthrough infections with different SARS-CoV-2 variants in a large cohort study with vaccinated cancer patients. 760 cancer patients were longitudinally followed-up, starting before first vaccination until six months after second booster. Anti-S1 SARS-CoV-2 IgGs were quantified in serum samples (N = 2958) and breakthrough infections were monitored using questionnaires, routine COVID-19 testing and medical chart review. A Generalized Estimating Equations approach was used to model the binary infection status as endpoint in relation to anti-S1 IgG titers. It is observed that higher anti-S1 IgG titers correspond to a lower probability of breakthrough infection. For the early pandemic phase, a protective anti-S1 IgG titer above 20.42 BAU/mL was observed. However, with the emergence of the Omicron variant, higher anti-S1 IgG titers are required to be protective, but no clear CoP could be identified.