Discussion
Among 396 residents from 7 NHs facing a VOC-α outbreak over 14 days after the end of a BNT162b2/Pfizer vaccination campaign, 103 had a positive RT-PCR test. After two vaccine doses, the risk of incident VOC-α infection was reduced by 48% when compared to non-vaccinated residents, and by 26% in residents with one dose. In RT-PCR-positive residents, two vaccine doses reduced the risk of severe symptoms by 56% (from 47.6% to 21.1%), and Covid-19 death by 82.4% (from 23.8% to 4.2%). Post-vaccine RBD-IgG levels under 1,050 AU/mL were associated with (i) an increased risk of incident VOC-α infection, (ii) a low serum neutralizing effect against SARS-CoV-2 wild type and VOC-α, and (iii) high levels of N-Ag that were associated with a higher risk of severe Covid-19 (severe symptoms, high C-reactive protein, low glomerular filtration rate).
The 48% reduction of SARS-CoV-2 infection after two vaccine doses found in the present study is consistent with NH studies reporting a VOC-α outbreak, even if the percentage of infected residents differed among the vaccinated and non-vaccinated. 2,4,9 The reduction in Covid-19 risk was estimated at 65% after a single BNT162b2/Pfizer vaccine dose in a national data study in England. 29The strong reduction of severe symptoms and death found in vaccinated residents was also reported. 4,9
In contrast to two previous studies, 2,30 we did not find any difference in viral load, estimated by the mean Ct. Because Ct values, vaccine regimen, and Covid-19 severity strongly differed between the three studies, further investigations are needed to determine the reduction of the viral load in infected residents after vaccination. This information is crucial to minimize the duration and consequences of isolation in vaccinated infected residents.
A novel result of the present study is that post-vaccine RBD-IgG levels can partly predict the efficacy of the vaccine in to prevent incident SARS-CoV-2 and severe symptoms. This is consistent with This result is also consistent with he lack of neutralizing effect observed in the serum against SARS-CoV-2 in vitro under a threshold of 1,050 AU/mL and the association between RBD-IgG levels and serum neutralization activity found above this threshold. In addition, lower RBD-IgG levels were significantly associated with higher N-Ag levels which were associated with a higher risk of Covid-19 severity (more severe symptoms, higher C-Reactive Protein levels and lower glomerular filtration rate - two biological markers of Covid-19 severity)18,19 which is in line with previous studies conducted in the general population. 31 Our results are consistent with studies in the general population showing a correlation between RBD-IgG and serum neutralization, 32,33 These studies combine to suggest that (i) low RBD-IgG levels following vaccination may not necessarily possess the key footprints required to block viral infection, and (ii) a minimal post-vaccine RBD-IgG level, possibly over 1,050 AU/mL, may be required to block VOC-α infection and/or prevent severe symptoms.
The strengths of this study include the sample size, and all studied NHs followed the same IPC guidance, making it possible to compare the results.21,22
This study also has several limitations: (i) RBD-IgG levels were measured using an immunoassay and results expressed in arbitrary units. However, the assay used in our study can probably be considered as a quantitative assay (<3.5% imprecision). 34(ii) RBD-IgG levels were measured within five days after the diagnosis of the first RT-PCR-positive resident of the NH. Even if this delay was as short as possible, RDB-IgG levels may also reflect a possible rapid anamnestic response to infection. This bias tends however to reinforce our results, since we found a relationship between low levels of RBD-IgG and a higher risk of SARS-CoV-2. (iii) Although the NH residents of the present study were comparable to the French NH population in terms of mean age, gender, and comorbidity status, our results obtained in residents exposed to a high risk of infection may not be extrapolated to all NH residents. (iv) Our results are only valuable for NHs facing a VOC-α outbreak. RBD-IgG produced by vaccinated residents seems less effective for binding and neutralizing in vitro β, δ, κ and ε variants 13 14-17,35 than the SARS-CoV-2 “wild type”.  14-17,35,36 (v) The results obtained are restricted to the BNT162b2/Pfizer vaccination in NH residents. Further studies conducted in NH residents facing other variants and different vaccines are therefore necessary. In this study, 8.7% of residents with RBD-IgG levels of over 4,160 AU/mL developed a positive RT-PCR. This suggests that vaccinated residents, even with high levels of S-protein IgG after two vaccine doses, may participate in SARS-CoV-2 transmission while most often being asymptomatic or pauci-symptomatic. These results suggest that vaccinated residents should be included in the wide-facility testing strategy when a resident is infected.