key: cord-0973768-d0n3r0ap
authors: Randad, P. R.; Pisanic, N.; Kruczynski, K.; Howard, T.; Gregory Rivera, M.; Spicer, K.; Antar, A. A. R.; Penson, T.; Thomas, D. L.; Pekosz, A.; Ndahiro, N.; Aliyu, L.; Betenbaugh, M. J.; Manley, H.; Detrick, B.; Katz, M.; Cosgrove, S.; Rock, C.; Zyskind, I.; Silverberg, J. I.; Rosenberg, A. Z.; Duggal, P.; Manabe, Y. C.; Collins, M. H.; Heaney, C. D.
title: Durability of SARS-CoV-2-specific IgG responses in saliva for up to 8 months after infection
date: 2021-03-15
journal: nan
DOI: 10.1101/2021.03.12.21252149
sha: 8130291ea5449efb58ed937297dbcfb629197c0b
doc_id: 973768
cord_uid: d0n3r0ap

We evaluated the durability of IgG responses specific to SARS-CoV-2 nucleocapsid (N), receptor binding domain (RBD), and spike (S) antigens in saliva up to 8 months after RT-PCR-confirmed COVID-19 using a multiplex salivary assay. We estimated a half-life of 64 days (d) (95% CI: 49, 80 d) for N, 100 d for RBD (95% CI: 58, 141 d), and 148 d (95% CI: 62, 238 d) for S IgG responses in saliva, consistent with half-life estimates previously reported in blood. Saliva can serve as an alternative to blood to monitor humoral immune responses on a large scale following natural SARS-CoV-2 infection and vaccination for surveillance and assessment of population immunity.

We evaluated the durability of IgG responses specific to SARS-CoV-2 nucleocapsid (N), receptor 53 binding domain (RBD), and spike (S) antigens in saliva up to 8 months after RT-PCR-confirmed COVID-54 19 using a multiplex salivary assay. We estimated a half-life of 64 days (d) (95% CI: 49, 80 d) for N, 100 55 d for RBD (95% CI: 58, 141 d), and 148 d (95% CI: 62, 238 d) for S IgG responses in saliva, consistent 56 with half-life estimates previously reported in blood. Saliva can serve as an alternative to blood to 57 monitor humoral immune responses on a large scale following SARS-CoV-2 infection and vaccination 58 for surveillance and assessment of population immunity. 59 . 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.

The copyright holder for this preprint this version posted March 15, 2021. ; https://doi.org/10.1101/2021.03.12.21252149 doi: medRxiv preprint There is a critical role for robust techniques to track humoral responses on a large scale following 61 SARS-CoV-2 infection and vaccination for surveillance and assessment of population immunity. We 62 previously developed and validated a multiplex bead-based immunoassay for detecting antibody 63 responses to SARS-CoV-2 N, RBD, and S antigens in oral fluid (hereafter, saliva). 1,2 In this study, we 64 apply this salivary assay to 531 saliva samples from 341 individuals up to 8 months after RT-PCR-65 confirmed SARS-CoV-2 infection to evaluate the durability of SARS-CoV-2 IgG responses. We 66 hypothesized that the durability of SARS-CoV-2 N, RBD, and S IgG in saliva would exceed at least six 67 months, comparable to those reported in blood. 3-5 68 SARS-CoV-2 N, RBD, and S IgG and the sum of their signal-to-cut off values (Σ[S/CO]) values 69 peaked in saliva at ~30 days post symptom onset (DPSO) (Fig. 1a) and 122 from males) between 1-6 months, and 73% (16/22; 10 from females and 12 from males) between 83 6-8 months (Fig. 1b) , indicating that most COVID-19 subjects are positive for SARS-CoV-2 IgG in 84 . 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)

The copyright holder for this preprint this version posted March 15, 2021. ; https://doi.org/10.1101/2021.03.12.21252149 doi: medRxiv preprint saliva up to 8 months post symptom onset and that incorporating the IgG response to multiple SARS-85

CoV-2 antigens can improve the sensitivity of saliva-based SARS-CoV-2 antibody testing. 86

There was evidence of a sex-specific interaction for N IgG and Σ[S/CO], with males having more 87 durable N IgG levels in saliva over time compared to females (n=265 saliva samples, 128 from 112 88 females and 137 from 122 males) (Fig. 2a, Supplementary Table 3 and 4) . In general, half-life 89 estimates for N, RBD, and S IgG in saliva were longer in males than females (Supplementary Table 3) . 90

We detected a trend of elevated RBD IgG and Σ[S/CO] in saliva of males compared to females 91 Table 5 analyzing SARS-CoV-2 IgG multiplex data in saliva. 106

These results demonstrate that SARS-COV-2 RBD and S IgG are durable in saliva for up to 8 107 months post symptom onset. Durability appears to be increased among males versus females and 108 . 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. 

COVID-19 serology at population scale: SARS-CoV-2-specific antibody 132 responses in saliva

Comparative performance of multiplex salivary and commercially available 134 serologic assays to detect SARS-CoV-2 IgG and neutralization titers. medRxiv : the preprint 135 server for health sciences

Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens 137 in COVID-19 patients

Immunological memory to SARS-CoV-2 assessed for up to 8 months after 139 infection. Science (80-. )

Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-141

Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike 144

Convergent antibody responses to SARS-CoV-2 in convalescent individuals

SARS-CoV-2, COVID-19, saliva, oral fluid, antibody, antibody testing, durability 30