key: cord-0830819-2nh1e5hw
authors: Blain, H.; TUAILLON, E.; Pisoni, A.; Soriteau, L.; Million, E.; Leglise, M.-S.; Bussereau, I.; Miot, S.; Rolland, Y.; Picot, M.-C.; Bousquet, J. J.
title: Prior Covid-19 and high RBD-IgG levels correlate with protection against VOC-delta SARS-CoV-2 infection in vaccinated Nursing Home Residents
date: 2021-09-21
journal: nan
DOI: 10.1101/2021.09.21.21263880
sha: 88c621cc21f047961339ae0ffcf07bd9afec8a4f
doc_id: 830819
cord_uid: 2nh1e5hw

Background Nursing Home (NH) residents are at high risk of serious illness and death from coronavirus disease 2019 (Covid-19), especially with the SARS-CoV-2 variants of concerns (VOC). It is unknown as to whether a history of Covid-19 prior to the vaccine and post-vaccine RBD-IgG levels are predictors of BNT162b2 vaccine effectiveness against VOC-delta in nursing home residents. Methods We analyzed the data from two NHs that faced a VOC-delta outbreak in July-August 2021. These NHs had suffered prior Covid-19 outbreaks in 2020 and 2021. In many of the residents, RBD-IgG levels were measured 6 weeks after the second vaccine dose, i.e. 3 to 5 months before the VOC-delta outbreak onset, and again during the outbreak (SARS-CoV-2 IgG II Quant assay, Abbott Diagnostics). We compared residents with vs without prior Covid-19 for (i) VOC-delta incidence, (ii) the correlation between post-vaccine RBD-IgG levels and VOC-delta incidence, and (iii) the time-related change in RBD-IgG levels. Results Among the 140 analyzed residents (58 to 101 years; 94 females, 46 men, mean age (SD): 84.6 yr (9.5 yr), one resident among the 44 with prior Covid-19 before vaccination developed a VOC-delta infection during the outbreak (1.3%) vs 55 of the 96 without Covid-19 prior to vaccination (57.3 %)(p<0.0001). The median value for RBD-IgG after the vaccine and during the outbreak was higher in residents with prior Covid-19 (31553 AU/mL and 22880 AU/mL) than in those without (1050 AU/mL and 260 AU/mL)(p<0.0001). In residents without Covid-19 prior to vaccination, post-vaccination RDB-IgG levels did not predict protection against VOC-delta infection. Conclusions In contrary to residents with prior SARS-CoV-2 infection, those without a history of Covid-19 before two BNT162b2 doses are not protected against VOC-delta infection and their RBD-Ig-G levels are low 3 to 5 months after vaccination. This suggests that a booster vaccine dose should be considered in this group of residents for a better protection against VOC-delta infection.

In contrary to residents with prior SARS-CoV-2 infection, those without a history of Covid-19 before two BNT162b2 doses are not protected against VOC-δ infection and their RBD-Ig-G levels are low 3 to 5 months after vaccination. This suggests that a booster vaccine dose should be considered in this group of residents for a better protection against VOC-δ infection.

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 21, 2021. ; https://doi.org/10.1101/2021.09.21.21263880 doi: medRxiv preprint

Nursing Home (NH) residents are at high risk of serious illness and death from coronavirus disease 2019 . Vaccination is safe and effective in adults, but is less documented in NH residents. 1 Outbreaks of SARS-CoV-2 'variants of concern' (VOC), especially VOC−δ, have recently been described in NHs in whom most of the residents had received two doses of the BNT162b2 vaccine. 2 In March 2020, the French Occitanie region set up 22 Covid-19 support platforms to help NHs implement the Occitanie Health Agency recommendations (derived from the European Geriatric Medicine Society (EuGMS) guidance 3 ) to prevent Covid-19 within their facilities. The Montpellier

Covid-19 platform provides support to 122 NHs and over 6,000 residents 4,5,6 Specifically, as soon as a first case of positive RT-PCR is diagnosed in a resident, the support platform helps the NH (i) to implement infection, prevention and control (IPC) measures, (ii) to test all residents and staff members using real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-PCR), and (iii) to retest all RT-PCR-negative individuals weekly until no new cases are diagnosed for at least 14 days. 4, 6 In collaboration with the platform, NHs may assess N-protein IgG levels in residents for whom prior Covid-19 is suspected to confirm diagnosis and post-vaccine S-protein (RBD)-IgG levels, in order to reinforce IPC measures in individuals with low post-vaccine antibody response.

We observed that a single dose of the BNT162b2 vaccine was sufficient in most NH residents with prior Covid-19 to obtain RBD-IgG levels of over 4,160 AU/mL, threshold associated with a high invitro neutralizing activity and equivalent to 433 BAU/mL. In contrast, 6 weeks after the second vaccine dose, 30% of NH residents without prior Covid-19 had RBD-IgG levels below 1,050 AU/mL, threshold predicting a neutralizing effect of the serum against SARS-CoV-2 in vitro. 7, 8, 9 The low immunogenicity of the vaccine in NH residents without prior Covid-19 and the fact that RBD-IgG produced by vaccinated and recovered individuals are less effective in binding and neutralizing in vitro VOC-β and δ than the "wild type" SARS-CoV-2 10,11 could in part explain the occurrence of VOC-δ outbreaks in NHs in which most of the residents are vaccinated.

To determine whether vaccinated residents with Covid-19 before vaccination are more protected against the VOC-δ than those without, and whether residents with low post-vaccine RBD-IgG levels are at higher risk of incident VOC-δ, we analyzed the data from two NHs that faced a VOC-δ outbreak in July-August 2021. These facilities had already suffered prior Covid-19 outbreaks in 2020 and 2021.

In many of the residents, RBD-IgG levels were measured 6 weeks after the second vaccine dose, i.e. 1,5 to 3,5 months before the VOC-δ outbreak onset, and again during the outbreak. We compared residents with vs without Covid-19 before vaccination for (i) VOC-δ incidence, (ii) the correlation All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 21, 2021. ; https://doi.org/10.1101/2021.09.21.21263880 doi: medRxiv preprint between post-vaccine RBD-IgG levels and VOC-δ incidence, and (iii) the time-related change in RBD-IgG levels. 

RBD-IgG levels 6 weeks after the second vaccine dose were available in 84 residents (55.6 % of the whole sample, Table 2 ). All residents with prior Covid-19 before vaccination had post-vaccine RBD-IgG levels of over 1,050 AU/mL vs 4/25 (16%) residents without prior Covid-19 (p<0.0001). In residents without Covid-19 prior to vaccination, post-vaccination RBD-IgG levels did not predict the protection against VOC-δ infection.

immunization. The analysis conducted in residents who do not develop Covid-19 shows that residents with Covid-19 prior to vaccination maintain a high level of RBD IgG at the time of VOC-δ outbreak, i.e. 1,5 to 3,5 months after vaccination, whereas most of the residents without Covid-19 before vaccination have low RBD-IgG levels at that time. RBD-IgG levels 6 weeks after the vaccine of residents without a Covid-19 history are comparable in those who developed or did not develop VOCδ some months later. Thus, most of the residents without prior Covid-19 before vaccination had probably low RBD-IgG levels by the time the VOC-δ outbreak started in their NH. In this group, memory B cells and secondary immune response were probably most often not sufficient to prevent Covid-19. This result supports the hypothesis that a minimal post-vaccine RBD-IgG level may be required to block VOC-δ infection in NH residents, and that this minimal level is observed mainly in residents with Covid-19 prior to vaccination, and far less in those without. This result supports that a booster vaccine dose given less than 6 months after the second dose should be considered in NH residents without Covid-19 infection prior to vaccination in order better protect them against VOC-δ infection risk. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 21, 2021. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 21, 2021. ; https://doi.org/10.1101/2021.09.21.21263880 doi: medRxiv preprint

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