key: cord-0426623-4ylt5rhg
authors: Canaday, D. H.; Oyebanji, O.; Keresztesy, D.; Payne, M.; WIlk, D.; Caris, L.; Aung, H.; St. Denis, K.; Lam, E.; Rowley, C.; Berry, S.; Cameron, C.; Cameron, M.; Wilson, B.; Balazs, A.; King, C.; Gravenstein, S.
title: Significant reduction in humoral immunity among healthcare workers and nursing home residents 6 months after COVID-19 BNT162b2 mRNA vaccination
date: 2021-08-18
journal: nan
DOI: 10.1101/2021.08.15.21262067
sha: eea9c13b7cc06b77f0549e26231a6ec04b72ff35
doc_id: 426623
cord_uid: 4ylt5rhg

CoV-2 vaccination; most NH residents received BNT162b2 mRNA vaccination under the Emergency Use Authorization due to first to market and its availability. With NH residents poor initial vaccine response, the rise of NH breakthrough infections and outbreaks, characterization of the durability of immunity to inform public health policy on the need for boosting is needed. We report on humoral immunity from 2 weeks to 6-months post-vaccination in 120 NH residents and 92 ambulatory healthcare worker controls with and without pre-vaccination SARS-CoV-2 infection. Anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, were assessed using a bead-based ELISA method and pseudovirus neutralization assay. Anti-spike, anti-RBD and neutralization levels dropped more than 80% over 6 months time in all groups irrespective of prior SARS-CoV-2 infection. At 6 months post-vaccine, 72% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection compared to 16% at 2 weeks after full vaccination. These data demonstrate a significant reduction in levels of antibody in all groups. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. Based on the rapid spread of the delta variant and reports of vaccine breakthrough in NH and among younger community populations, boosting NH residents may be warranted.

s t e f a n _ g r a v e n s t e i n @ b r o w n . e d u

High COVID-19 mortality among nursing home (NH) residents led to their prioritization for SARS-CoV-2 vaccination; most NH residents received BNT162b2 mRNA vaccination under the Emergency Use Authorization due to first to market and its availability. With NH residents' poor initial vaccine response, the rise of NH breakthrough infections and outbreaks, characterization of the durability of immunity to inform public health policy on the need for boosting is needed. We report on humoral immunity from 2 weeks to 6-months post-vaccination in 120 NH residents and 92 ambulatory healthcare worker controls with and without pre-vaccination SARS-CoV-2 infection. Anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, were assessed using a bead-based ELISA method and pseudovirus neutralization assay. Anti-spike, anti-RBD and neutralization levels dropped more than 80% over 6 months' time in all groups irrespective of prior SARS-CoV-2 infection. At 6 months post-vaccine, 72% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection compared to 16% at 2 weeks after full vaccination. These data demonstrate a significant reduction in levels of antibody in all groups. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. Based on the rapid spread of the delta variant and reports of vaccine breakthrough in NH and among younger community populations, boosting NH residents may be warranted.

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.15.21262067 doi: medRxiv preprint

The very high overall COVID-19 morbidity and mortality among nursing home (NH) residents led to their prioritization as a population for early vaccination. In the US, most NH residents received BNT162b2 mRNA vaccination both because of its earlier approval under the Emergency Use Authorization (EUA) and availability compared to other candidate SARS-CoV-2 vaccines. Fully vaccinated NH residents produced about ¼ the antibody to this vaccine than healthy younger comparison populations [1, 2] . With the rise of breakthrough infections in NH residents and others with immunocompromise, there is a significant need for characterization of the durability of immunity to inform public health policy. We report on 2-week and 6-month post-vaccination antibody levels from 120 NH residents (age range 48-100, median 76) and 92 ambulatory healthcare worker controls (age range 26-78, median 48) with and without pre-vaccination SARS-CoV-2 infection. We assessed anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, using a bead-based ELISA method and pseudovirus neutralization assay [1, 3] . Anti-spike, anti-RBD and neutralization geometric mean levels dropped more than 80% over 6 months' time in all groups (Fig. 1a-c) irrespective of prior SARS-CoV-2 infection. At 6 months postvaccine, 72% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection (LLD, 1:12 titer) compared to 16% at the LLD at 2 weeks after full vaccination (Table 1) . Controls and NH residents who survived prior infection had ≤ 9% below LLD at a 1:12 dilution of the neutralization assay at 2 weeks and 6 months post-vaccination. These data demonstrate a significant reduction in levels of antibody in all groups.

An improved understanding of the clinical consequences of this drop in humoral immunity is urgently needed to optimally inform boosting strategies and policy that are being actively considered. However, in the absence of clinical evidence, extrapolating from laboratory values may be necessary. NH residents and healthcare workers were amongst the earliest populations vaccinated in the US and elsewhere, resulting in the longest time for immunity to wane. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. The rapid delta variant spread, vaccine breakthrough in NHs and community [4, 5] , and rapid antibody decline suggest boosting NH residents may be warranted to curb spread or prevent severe illness.

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; (Figure 1c ) are shown. Residents refers to NH residents and Control refers to younger healthcare workers. Prior infection refers to antibody levels at the given time points in individuals vaccinated after recovering from earlier SARS-CoV-2 infection, and infection naive refers to individuals vaccinated without prior SARS-CoV-2 infection. Geometric means in each group were assessed using paired t-tests of logtransformed values among subjects with both measures present. P values comparing the difference between 2 weeks and 6 months in all clinical groups were p<0.001. Subjects with large increases (>100%) of anti-spike, anti-RBD, or neutralizing titers from 2 weeks to 6 months were excluded due to presumed SARS-CoV-2 infection after vaccination.

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.15.21262067 doi: medRxiv preprint

Reduced BNT162b2 mRNA vaccine response in SARS-CoV-2-naive nursing home residents

Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination

COVID-19-neutralizing antibodies predict disease severity and survival

Postvaccination SARS-CoV-2 Infections Among Skilled Nursing Facility Residents and Staff Members

PubMed Central PMCID: PMCPMC8084122 Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed

Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings