Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 154 No. 7 (2024)

Anti-SARS-CoV-2 total immunoglobulin and neutralising antibody responses in healthy blood donors throughout the COVID-19 pandemic: a longitudinal observational study

DOI
https://doi.org/10.57187/s.3408
Cite this as:
Swiss Med Wkly. 2024;154:3408
Published
01.07.2024

Summary

INTRODUCTION: Quantifying antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neutralising antibodies may help to understand protection at the individual and population levels. Determination of neutralising antibodies using classical virus neutralisation tests (VNT) is considered the gold standard, but they are costly and time-intensive. Enzyme-linked immunosorbent assay (ELISA)-based surrogate VNTs (sVNT) or anti-SARS-CoV-2 spike protein receptor binding domain immunoglobulins (anti-S-RBD Ig) may be suitable alternatives to VNTs. We aimed to (a) explore the correlations between anti-S-RBD Ig, VNT, and sVNT measurements and (b) describe humoral immunity against SARS-CoV-2 after vaccination, natural infection, and vaccine breakthrough infection in healthy blood donors.

METHODS: We measured total anti-SARS-CoV-2 Ig in 5714 serum samples from 2748 healthy individuals visiting the Swiss Red Cross Blood Donation Centre in Basel from 03/2020 to 04/2022. We used the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche) against the N- and S-receptor binding domain (RBD) proteins. In a subset of 548 samples from 123 donors, we conducted sVNTs against the Wuhan wild-type SARS-CoV-2 (SARS-CoV-2 Neutralizing Antibodies Detection Kit; Adipogen™). In 100 samples from 40 donors, we correlated sVNT and VNTs against the wild-type (D614G WU1) virus. Surveys were sent to the blood donors to collect data on their SARS-CoV-2 infection and vaccination status. Using this data, donors were categorised as “vaccination only”, “infection before vaccination”, “post-vaccine breakthrough infection”, and “natural infection only”.

RESULTS: Our longitudinal observation study cohort consisted of 50.7% males with a median age of 31 years (range 18–75 y). Anti-SARS-CoV-2 N protein positivity rates per month indicate 57.1% (88/154) of the cohort was infected up to 04/2022. No differences in seropositivity were found between sexes, age groups, blood types (AB0 or RhD), and cytomegalovirus serostatus. We observed a high correlation between anti-S-RBD Ig and inhibition percentage (Spearman’s ρ = 0.92, Kendall’s τ = 0.77, p <0.0001). We determined the sensitivity and specificity for the manufacturers’ thresholds for detecting virus-neutralising effects and computed the “best” cut-off based on our real-world data. We categorised 722/1138 (63.5%) donors as vaccination only (82.3%), post-vaccine breakthrough infection (7.8%), infection before vaccination (5.8%), and natural infection only (4.2%). We observed a lower inhibition percentage in the natural infection-only group than in all other vaccinated groups. The infection before vaccination group had higher anti-S-RBD Ig titres after the first vaccine dose than the other vaccinated groups.

CONCLUSION: In total, 57.1% of healthy blood donors were infected with SARS-CoV-2, but natural infection without evidence of vaccination seems to result in substantially lower neutralising antibody levels. An estimate of antibody neutralisation may be helpful to assess reinfection risk. Total anti-S-RBD Ig correlates with surrogate virus neutralisation test results, a surrogate for neutralisation; therefore, we suggest that total anti-S-RBD Ig may estimate the level of neutralising antibodies. The threshold for protection from an unfavourable clinical outcome must be evaluated in prospective clinical cohorts.

References

  1. Robinson ML, Morris CP, Betz JF, Zhang Y, Bollinger R, Wang N, et al. Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Variants on Inpatient Clinical Outcome. Clin Infect Dis. 2023 May;76(9):1539–49. 10.1093/cid/ciac957 DOI: https://doi.org/10.1093/cid/ciac957
  2. Li K, Huang B, Wu M, Zhong A, Li L, Cai Y, et al. Dynamic changes in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery from COVID-19. Nat Commun. 2020 Nov;11(1):6044. 10.1038/s41467-020-19943-y DOI: https://doi.org/10.1038/s41467-020-19943-y
  3. Wheatley AK, Fox A, Tan HX, Juno JA, Davenport MP, Subbarao K, et al. Immune imprinting and SARS-CoV-2 vaccine design. Trends Immunol. 2021 Nov;42(11):956–9. 10.1016/j.it.2021.09.001 DOI: https://doi.org/10.1016/j.it.2021.09.001
  4. Ju B, Zhang Q, Ge J, Wang R, Sun J, Ge X, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020 Aug;584(7819):115–9. 10.1038/s41586-020-2380-z DOI: https://doi.org/10.1038/s41586-020-2380-z
  5. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021 Jul;27(7):1205–11. 10.1038/s41591-021-01377-8 DOI: https://doi.org/10.1038/s41591-021-01377-8
  6. Addetia A, Crawford KH, Dingens A, Zhu H, Roychoudhury P, Huang ML, et al. Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate. J Clin Microbiol. 2020 Oct;58(11):e02107-20. 10.1128/jcm.02107-20 10.1128/JCM.02107-20 DOI: https://doi.org/10.1128/JCM.02107-20
  7. Manenti A, Maggetti M, Casa E, Martinuzzi D, Torelli A, Trombetta CM, et al. Evaluation of SARS-CoV-2 neutralizing antibodies using a CPE-based colorimetric live virus micro-neutralization assay in human serum samples. J Med Virol. 2020 Oct;92(10):2096–104. 10.1002/jmv.25986 DOI: https://doi.org/10.1002/jmv.25986
  8. Ghasemiyeh P, Mohammadi-Samani S, Firouzabadi N, Dehshahri A, Vazin A. A focused review on technologies, mechanisms, safety, and efficacy of available COVID-19 vaccines. Int Immunopharmacol. 2021 Nov;100:108162. 10.1016/j.intimp.2021.108162 DOI: https://doi.org/10.1016/j.intimp.2021.108162
  9. Elecsys® Anti-SARS-CoV-2 S [Internet]. [cited 2023 Mar 7]. Available from: https://diagnostics.roche.com/global/en/products/params/elecsys-anti-sars-cov-2-s.html#productInfo
  10. R Core Team. R: A Language and Environment for Statistical Computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing; 2023. Available from: https://www.R-project.org
  11. Wickham H, Averick M, Bryan J, Chang W, McGowan LD, François R, et al. Welcome to the Tidyverse. J Open Source Softw. 2019 Nov;4(43):1686. 10.21105/joss.01686 DOI: https://doi.org/10.21105/joss.01686
  12. Sachs MC. plotROC: A Tool for Plotting ROC Curves. J Stat Softw. 2017 Aug;79 Code Snippet 2:1–19. 10.18637/jss.v079.c02 DOI: https://doi.org/10.18637/jss.v079.c02
  13. Controlling the False Discovery Rate. A Practical and Powerful Approach to Multiple Testing - Benjamini - 1995 - Journal of the Royal Statistical Society: Series B (Methodological) - Wiley Online Library [Internet]. [cited 2023 Feb 2]. Available from: https://rss.onlinelibrary.wiley.com/doi/10.1111/j.2517-6161.1995.tb02031.x
  14. Chen C, Nadeau S, Yared M, Voinov P, Xie N, Roemer C, et al. CoV-Spectrum: analysis of globally shared SARS-CoV-2 data to identify and characterize new variants. Bioinformatics. 2022 Mar;38(6):1735–7. 10.1093/bioinformatics/btab856 DOI: https://doi.org/10.1093/bioinformatics/btab856
  15. Coronavirus (COVID-19): Tests Basel-Stadt [Internet]. [cited 2023 Feb 5]. Available from: https://data.bs.ch/explore/dataset/100094/table/
  16. Coronavirus (Covid-19): Geimpfte Personen mit Wohnsitz in Basel-Stadt [Internet]. [cited 2023 Feb 5]. Available from: https://data.bs.ch/explore/dataset/100162/table/
  17. Notarte KI, Ver AT, Velasco JV, Pastrana A, Catahay JA, Salvagno GL, et al. Effects of age, sex, serostatus, and underlying comorbidities on humoral response post-SARS-CoV-2 Pfizer-BioNTech mRNA vaccination: a systematic review. Crit Rev Clin Lab Sci. 2022 Sep;59(6):373–90. 10.1080/10408363.2022.2038539 DOI: https://doi.org/10.1080/10408363.2022.2038539
  18. Pellini R, Venuti A, Pimpinelli F, Abril E, Blandino G, Campo F, et al. Initial observations on age, gender, BMI and hypertension in antibody responses to SARS-CoV-2 BNT162b2 vaccine. EClinicalMedicine. 2021 Jun;36:100928. 10.1016/j.eclinm.2021.100928 DOI: https://doi.org/10.1016/j.eclinm.2021.100928
  19. Salvagno GL, Henry BM, di Piazza G, Pighi L, De Nitto S, Bragantini D, et al. Anti-SARS-CoV-2 Receptor-Binding Domain Total Antibodies Response in Seropositive and Seronegative Healthcare Workers Undergoing COVID-19 mRNA BNT162b2 Vaccination. Diagnostics (Basel). 2021 May;11(5):832. 10.3390/diagnostics11050832 DOI: https://doi.org/10.3390/diagnostics11050832
  20. Kitagawa Y, Imai K, Matsuoka M, Fukada A, Kubota K, Sato M, et al. Evaluation of the correlation between the access SARS-CoV-2 IgM and IgG II antibody tests with the SARS-CoV-2 surrogate virus neutralization test. J Med Virol. 2022 Jan;94(1):335–41. 10.1002/jmv.27338 DOI: https://doi.org/10.1002/jmv.27338
  21. Bates TA, McBride SK, Leier HC, Guzman G, Lyski ZL, Schoen D, et al. Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants. Sci Immunol. 2022 Feb;7(68):eabn8014. 10.1126/sciimmunol.abn8014 DOI: https://doi.org/10.1126/sciimmunol.abn8014
  22. Wang Z, Muecksch F, Schaefer-Babajew D, Finkin S, Viant C, Gaebler C, et al. Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature. 2021 Jul;595(7867):426–31. 10.1038/s41586-021-03696-9 DOI: https://doi.org/10.1038/s41586-021-03696-9
  23. Turner JS, O’Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature. 2021 Aug;596(7870):109–13. 10.1038/s41586-021-03738-2 DOI: https://doi.org/10.1038/s41586-021-03738-2
  24. Al-Sadeq DW, Shurrab FM, Ismail A, Amanullah FH, Thomas S, Aldewik N, et al. Comparison of antibody immune responses between BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in naïve and previously infected individuals. J Travel Med. 2021 Dec;28(8):taab190. 10.1093/jtm/taab190 DOI: https://doi.org/10.1093/jtm/taab190
  25. Assis R, Jain A, Nakajima R, Jasinskas A, Khan S, Palma A, et al. Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination. npj. Vaccines (Basel). 2021 Nov;6(1):1–10. DOI: https://doi.org/10.1038/s41541-021-00396-3
  26. Leuzinger K, Osthoff M, Dräger S, Pargger H, Siegemund M, Bassetti S, et al. Comparing Immunoassays for SARS-CoV-2 Antibody Detection in Patients with and without Laboratory-Confirmed SARS-CoV-2 Infection. J Clin Microbiol. 2021 Nov;59(12):e0138121. 10.1128/jcm.01381-21 10.1128/JCM.01381-21 DOI: https://doi.org/10.1128/JCM.01381-21
  27. Baral P, Bhattarai N, Hossen ML, Stebliankin V, Gerstman BS, Narasimhan G, et al. Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B.1.617.2 and implications for immune evasion. Biochem Biophys Res Commun. 2021 Oct;574:14–9. 10.1016/j.bbrc.2021.08.036 DOI: https://doi.org/10.1016/j.bbrc.2021.08.036
  28. Lee J, Lee DG, Jung J, Ryu JH, Shin S, Cho SY, et al. Comprehensive assessment of SARS-CoV-2 antibodies against various antigenic epitopes after naive COVID-19 infection and vaccination (BNT162b2 or ChAdOx1 nCoV-19) [Internet]. Front Immunol. 2022 Dec;13:1038712. [cited 2023 Jun 8] Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1038712 10.3389/fimmu.2022.1038712 DOI: https://doi.org/10.3389/fimmu.2022.1038712
  29. Muruato AE, Fontes-Garfias CR, Ren P, Garcia-Blanco MA, Menachery VD, Xie X, et al. A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation. Nat Commun. 2020 Aug;11(1):4059. 10.1038/s41467-020-17892-0 DOI: https://doi.org/10.1038/s41467-020-17892-0
  30. Bekliz M, Adea K, Vetter P, Eberhardt CS, Hosszu-Fellous K, Vu DL, et al. Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs. Nat Commun. 2022 Jul;13(1):3840. 10.1038/s41467-022-31556-1 DOI: https://doi.org/10.1038/s41467-022-31556-1
  31. Lau EH, Hui DS, Tsang OT, Chan WH, Kwan MY, Chiu SS, et al. Long-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection [Internet]. EClinicalMedicine. 2021 Nov;41:101174. [cited 2023 Aug 9] Available from: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00454-5/fulltext 10.1016/j.eclinm.2021.101174 DOI: https://doi.org/10.1016/j.eclinm.2021.101174
  32. Perera RA, Mok CK, Tsang OT, Lv H, Ko RL, Wu NC, et al. Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020. Euro Surveill. 2020 Apr;25(16):2000421. 10.2807/1560-7917.ES.2020.25.16.2000421 DOI: https://doi.org/10.2807/1560-7917.ES.2020.25.16.2000421
  33. Kohmer N, Rühl C, Ciesek S, Rabenau HF. Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies. J Clin Med. 2021 May;10(10):2128. 10.3390/jcm10102128 DOI: https://doi.org/10.3390/jcm10102128

Most read articles by the same author(s)

1 2 > >>