key: cord-0300373-vk0j944j
authors: Zhong, D.; Xiao, S.; Debes, A. K.; Egbert, E. R.; Caturegli, P.; Colantuoni, E.; Milstone, A. M.
title: Impact of prior SARS-CoV-2 infection on post-vaccination SARS-CoV-2 spike IgG antibodies in a longitudinal cohort of healthcare workers
date: 2021-09-22
journal: nan
DOI: 10.1101/2021.09.16.21263576
sha: 35103e932ef489a25d43b73441782bda6e6bfc33
doc_id: 300373
cord_uid: vk0j944j

Waning serum antibodies against SARS-CoV-2 have sparked discussions about long-term immunity and need for vaccine boosters. We examined SARS-CoV-2 spike IgG antibodies in a longitudinal cohort, comparing antibody decay in individuals who received an mRNA SARS-CoV-2 vaccine, with and without prior SARS-CoV-2 infection. We completed a longitudinal cohort of healthcare workers (HWs) between June 2020 and September 2021. HWs were included if they had a serum sample collected after SARS-CoV-2 infection and/or a serum sample collected [≥] 14 days after second dose of an mRNA SARS-CoV-2 vaccine. Linear regression models adjusting for vaccine type, age, and sex were used to compare post-vaccination antibody levels between 1) HWs with and without prior SARS-CoV-2 infection and 2) HWs with prior SARS-CoV-2 infection [≤] 90 days and > 90 days prior to first vaccine. Serum was collected from 98 HWs after SARS-CoV-2 infection and before vaccine, and 1960 HWs [≥] 14 days following second vaccine dose. Serum spike antibody levels were higher after vaccination than after natural infection. Compared to SARS-CoV-2 naive individuals, those with prior infection maintained higher post-vaccination mean spike IgG values at 1, 3, and 6 months, after adjusting for age, sex, and vaccine type. Individuals with PCR-confirmed infection > 90 days before vaccination had higher post-vaccination antibody levels than individuals infected [≤] 90 days before vaccination. Individuals with three exposures to spike protein maintain the highest antibody levels particularly when first and second exposures were greater than 90 days apart. A booster dose provides a third exposure and may similarly induce a more durable antibody response.

Waning serum antibodies against SARS-CoV-2 have sparked intense public health interest about long-term immunity. Lower antibody levels to SARS-CoV-2 spike protein are associated with breakthrough infections after vaccination, prompting consideration of booster . CC-BY-NC-ND 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) preprint

The copyright holder for this this version posted September 22, 2021. ; https://doi.org/10.1101/2021.09.16.21263576 doi: medRxiv preprint doses. 1, 2 Prior infection may enhance protection from vaccination, stimulating inquiry about the impacts of hybrid immunity. Our objective was to examine SARS-CoV-2 spike IgG antibodies in a longitudinal cohort, comparing antibody decay in individuals who received an mRNA SARS-CoV-2 vaccine, with and without prior SARS-CoV-2 infection.

Healthcare workers (HWs) were consented and enrolled starting June 3, 2020 and followed through September 3, 2021. HWs provided serum samples longitudinally, separated by at least 90 days. SARS-CoV-2 PCR results and vaccination dates were collected from electronic health records. HWs were included if they had a serum sample collected after SARS-CoV-2 infection (defined as positive SARS-CoV-2 PCR), and/or a serum sample collected ≥ 14 days after second dose of an mRNA SARS-CoV-2 vaccine. Serum was tested using an enzymelinked immunosorbent assay (ELISA) [Euroimmun], as previously described. 3, 4 Linear regression models adjusting for vaccine type, age, and sex were used to compare postvaccination antibody levels (log-transformed) between 1) HWs with and without prior SARS-CoV-2 infection and 2) HWs with prior SARS-CoV-2 infection ≤ 90 days and > 90 days prior to first vaccine. Ethical approval was obtained from the Johns Hopkins University Institutional Review Board. Analyses were performed in R, version 4.0.2. Serum spike antibody levels were higher after vaccination than after natural infection ( Figure 1a ). Compared to SARS-CoV-2 naïve individuals, those with prior infection maintained . CC-BY-NC-ND 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) preprint

The copyright holder for this this version posted September 22, 2021. ; https://doi.org/10.1101/2021.09.16.21263576 doi: medRxiv preprint higher post-vaccination mean spike IgG values by 14, 19 and 56 percent at 1, 3, and 6 months, respectively, after adjusting for age, sex, and vaccine type (Table 1) . Individuals with PCRconfirmed infection > 90 days before vaccination had higher post-vaccination antibody levels than individuals infected ≤ 90 days before vaccination by roughly 10 percent, at 1 and 3 months ( Figure 1b ).

Our study demonstrates that HWs who received two doses of mRNA vaccine maintain Days following completion of 2nd mRNA vaccine Ratio of serum IgG antibodies to spike S1 subunit Vaccinated <= 90 days after infection Vaccinated > 90 days after infection

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IQR -interquartile range a Adjusted median IgG were estimated from linear regression models of log-transformed antibody level as a function of time (natural cubic spline with 2 degrees of freedom), group, interaction of time and group adjusting for vaccine type, age and sex. The 95% CIs for adjusted median IgG and relative median were constructed via the percentile bootstrap procedure using 1,000 bootstrap samples of HWs to account for clustering of serum samples within HWs

Adjusted median IgG and relative median at 6 months were not estimated for healthcare workers with prior SARS-CoV-2 infection ≤ 90 days and > 90 days prior to first vaccine dose separately due to few data points beyond 150 days