Strengths and limitations of the study
This study has several strengths. Our sample is probably representative of the population of NH residents in France since it was conducted on a large sample of residents who were tested across 22 NHs facing a COVID-19 outbreak. Ascertainment of positive and negative RT-PCR results is probably almost complete since all studied NHs followed the same regional Health Agency guidance published in March 20202,3. We used an automated quantitative assay to measure the RBD IgG level that correlates well with virus neutralisation37,38. N-protein IgG measurement in all individuals allowed us to differentiate residents with SARS-CoV-2 immunisation while having repeated negative RT-PCR tests.
The main limitation of the study is the lack of clinical outcome. It remains indeed to demonstrate that a single BNT162b2 jab in residents having recovered from COVID-19 has the same efficacy in preventing reinfection as two doses. If the N-protein IgG level is associated with a substantially reduced risk of SARS-CoV-2 reinfection8, there is no available publication demonstrating a link between the S-protein IgG level obtained after the vaccine and the risk of incident SARS-CoV-2 infection and of symptomatic or severe COVID-19. It remains to be determined whether the thresholds we have chosen to define a low level (≤ 1050 AU/mL) or a high S-protein IgG after the vaccine (≥ 4,160 AU/mL) are effectively associated with an increased or decreased risk of developing SARS-CoV-2 infection.7 This is particularly important since serum neutralising activities against SARS-CoV-2 six months after COVID-19 hospitalisation remain significant for ancestral strains and for the D614G and B.1.16 variants but are weaker for the B.1.351 variant39. It is therefore plausible that the post-vaccine S-protein IgG level necessary to obtain protection against new variants may be higher than previously defined 40.