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Observational Study
. 2020 Oct 8;5(52):eabe5511.
doi: 10.1126/sciimmunol.abe5511.

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

Baweleta Isho #  1 , Kento T Abe #  2   3 , Michelle Zuo #  1 , Alainna J Jamal #  4   5 , Bhavisha Rathod  2 , Jenny H Wang  2 , Zhijie Li  3 , Gary Chao  1 , Olga L Rojas  1 , Yeo Myong Bang  1 , Annie Pu  1 , Natasha Christie-Holmes  6 , Christian Gervais  7 , Derek Ceccarelli  2 , Payman Samavarchi-Tehrani  2 , Furkan Guvenc  3 , Patrick Budylowski  6   8 , Angel Li  5 , Aimee Paterson  5 , Feng Yun Yue  1 , Lina M Marin  9 , Lauren Caldwell  2 , Jeffrey L Wrana  2   3 , Karen Colwill  2 , Frank Sicheri  2   3 , Samira Mubareka  10 , Scott D Gray-Owen  3   6 , Steven J Drews  11 , Walter L Siqueira  9 , Miriam Barrios-Rodiles  2 , Mario Ostrowski  1   12   13 , James M Rini  3   14 , Yves Durocher  7 , Allison J McGeer  2   4   5 , Jennifer L Gommerman  15 , Anne-Claude Gingras  16   3
Affiliations
Observational Study

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

Baweleta Isho et al. Sci Immunol. .

Abstract

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Longitudinal analysis revealed that anti-SARS-CoV-2 IgA and IgM antibodies rapidly decayed, while IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

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Figures

Fig. 1
Fig. 1. Cross-sectional analysis of IgG and IgA responses to the spike and RBD antigens of SARS-CoV2 in serum.
(A-F) Indicated immunoglobulins to spike and RBD were profiled by ELISA in cohorts of pre-COVID samples (n=300), hospitalized patients with acute COVID infection (n=132) and convalescent patients (n=364). All data, expressed as ratio-converted ELISA reads to a pool of convalescent samples (relative ratio), were plotted using bean plots. Solid bars denote the median and dotted line represents the median across all samples used in the plot. (G-I) levels of IgG (G), IgA (H) and IgM (I) to the RBD (y-axis) and spike (x-axis) antigens for the indicated patient groups. Spearman correlation coefficient is indicated. Mann-Whitney U test for significance was performed. n.s = not significant, *= p ≤ 0.05, **** = p < 0.0001.
Fig. 2
Fig. 2
Persistence of antibodies in the serum of affected individuals. (A-F) Binned ratio-converted ELISA reads (relative ratios to a pool of positive controls) of spike (A-C) and RBD (D-F) to the indicated antibodies, displayed as bean plots. (G) The results of the surrogate neutralization ELISA are also shown, expressed as an integrated score tabulating the area under the curve across the first two points of the dilution series (see Methods). Days PSO are binned in 15-day increments and are compared to pre-COVID samples (neg). Solid bars denote the median and dotted line represents the median across all samples used in the plot. For A–F, the number of samples per bin was: neg=300; 0–15=115; 16–30=41; 31–45=50; 46–60=71; 61–75=62; 76–90=100; 91–105=9. For G, all bins were n=20, with the exception of neg.=19 and 106–115=9 (all available samples).
Fig. 3
Fig. 3. A longitudinal analysis of IgG and IgA responses to the spike and RBD antigens of SARS-CoV2 in serum.
Analysis of the changes in the indicated Ig-antigen levels in patients profiled twice, in comparisons to the relative levels in pre-COVID negative controls (left). Dots represent individual serum samples collected at the indicated times, and the samples from the same patients are connected by the lines. A non-parametric loess function is shown as the blue line, with the grey shade representing the 95% confidence interval.
Fig. 4
Fig. 4. Cross-sectional analysis of antibody responses to the spike and RBD antigens of SARS-CoV-2 in saliva.
Saliva specimens from the cohort of COVID-19 patients were tested for the presence of IgG, IgA and IgM antibodies to SARS-CoV-2 spike and RBD antigens (Positive), comparing with a mixture of unexposed asymptomatic controls collected locally and pre-COVID era controls (Negative). In these cohort 2 samples collected in Salivettes® we had sufficient material to perform several dilutions and to generate an integrated score for each subject (see Methods). Because the saliva was not diluted during collection, we were able to derive the concentration of antibodies in both negative controls and COVID-19 patients. (A-C) Total IgG, IgA and IgM levels in the saliva. (D-I) Saliva data for negative controls versus COVID-19 patients. Solid bars denote the median and dotted line represents the median across all samples used in the plot. Mann-Whitney U test for significance was performed. **** = p < 0.0001, n.s. = not significant.
Fig. 5
Fig. 5. A cross-sectional analysis of antibody responses to the spike and RBD antigens of SARS-CoV-2 in saliva correlated with time PSO.
A second cohort of COVID-19 patients (n=90) was tested for the presence of IgG and IgA antibodies to SARS-CoV-2 spike and RBD antigens in the saliva, comparing with a mixture of unexposed negative controls collected locally and pre-COVID era negative controls. (A-F) Saliva data for all 6 antigen-specific ELISA readouts plotted as time PSO. Spearman correlation coefficients (ρ) and p-value are indicated. In multivariable analysis adjusted for age, sex and severity of illness, there was a significant decline in anti-RBD and anti-spike IgA, but not significant change in the level of anti-RBD or anti-spike IgG.
Fig. 6
Fig. 6
Correlation of IgG, IgA and IgM responses to the spike and RBD antigens in serum and saliva. (A-F) A subset of serum and saliva sample pairs (n=71) collected from the same patient within 4 days were analyzed for correlations in levels of anti-spike and anti-RBD IgG, IgA and IgM antibodies. For serum, data are presented as ratio-normalized ELISA reads, while the saliva results are expressed as an integrated score, as in previous figures. The data are presented on a logarithmic scale. Spearman correlation coefficient (ρ) and p-value are indicated.
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References

    1. Letko M., Marzi A., Munster V., Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 5, 562–569 (2020). 10.1038/s41564-020-0688-y - DOI - PMC - PubMed
    1. Berry J. D., Hay K., Rini J. M., Yu M., Wang L., Plummer F. A., Corbett C. R., Andonov A., Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology. MAbs 2, 53–66 (2010). 10.4161/mabs.2.1.10788 - DOI - PMC - PubMed
    1. Amanat F., Stadlbauer D., Strohmeier S., Nguyen T. H. O., Chromikova V., McMahon M., Jiang K., Arunkumar G. A., Jurczyszak D., Polanco J., Bermudez-Gonzalez M., Kleiner G., Aydillo T., Miorin L., Fierer D. S., Lugo L. A., Kojic E. M., Stoever J., Liu S. T. H., Cunningham-Rundles C., Felgner P. L., Moran T., García-Sastre A., Caplivski D., Cheng A. C., Kedzierska K., Vapalahti O., Hepojoki J. M., Simon V., Krammer F., A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med. 26, 1033–1036 (2020). 10.1038/s41591-020-0913-5 - DOI - PMC - PubMed
    1. Long Q. X., Liu B.-Z., Deng H.-J., Wu G.-C., Deng K., Chen Y.-K., Liao P., Qiu J.-F., Lin Y., Cai X.-F., Wang D.-Q., Hu Y., Ren J.-H., Tang N., Xu Y.-Y., Yu L.-H., Mo Z., Gong F., Zhang X.-L., Tian W.-G., Hu L., Zhang X.-X., Xiang J.-L., Du H.-X., Liu H.-W., Lang C.-H., Luo X.-H., Wu S.-B., Cui X.-P., Zhou Z., Zhu M.-M., Wang J., Xue C.-J., Li X.-F., Wang L., Li Z.-J., Wang K., Niu C.-C., Yang Q.-J., Tang X.-J., Zhang Y., Liu X.-M., Li J.-J., Zhang D.-C., Zhang F., Liu P., Yuan J., Li Q., Hu J.-L., Chen J., Huang A.-L., Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat. Med. 26, 845–848 (2020). 10.1038/s41591-020-0897-1 - DOI - PubMed
    1. Premkumar L., Segovia-Chumbez B., Jadi R., Martinez D. R., Raut R., Markmann A., Cornaby C., Bartelt L., Weiss S., Park Y., Edwards C. E., Weimer E., Scherer E. M., Rouphael N., Edupuganti S., Weiskopf D., Tse L. V., Hou Y. J., Margolis D., Sette A., Collins M. H., Schmitz J., Baric R. S., de Silva A. M., The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci. Immunol. 5, eabc8413 (2020). 10.1126/sciimmunol.abc8413 - DOI - PMC - PubMed

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