CONTINUING EDUCATION :: ANTIBODIES


from vaccination. A vaccinated person testing positive for antibody against vaccine targets (S or RBD), and negative for other antigens (N), suggests that they have vaccine-induced antibody produc- tion and were never infected with SARS- CoV-2.21


Conversely, a vaccinated person


testing positive for antibodies other than antibodies against vaccine targets, such as the N protein, suggests recent or past SARS-CoV-2 infection that could have occurred before or after vaccination.21 An unvaccinated individual testing posi- tive by any SARS-CoV-2 Ab test could, therefore, be indicative of recent or past infection.21


To date, no SARS-CoV-2 Ab


test has been authorized by FDA for this purpose, and the clinical utility of dif- ferentiating specific antibody response elicitors remains unelucidated.


Determining immunity status and need for booster SARS-CoV-2 Ab tests will also likely play a role in the development of future vac- cines by assessing efficacy of vaccines in clinical trials.35


For effective monitoring


of post-vaccination efficacy and predic- tion of immune status, SARS-CoV-2 Ab tests need to provide a quantitative result, detect the types of antibodies capable of conferring immunity (ex. neutralizing antibodies), and the test result must be correlated to a threshold cut-off that is known to confer immunity.39,40


Clinical


outcome studies to determine if universal antibody threshold can be established to indicate whether an individual is immune to infection or reinfection have not yet been completed. Such studies would need to include both SARS-CoV-2 infected and noninfected individuals who have or have not been vaccinated. As such, no existing SARS-CoV-2 Ab test can predict immunity status. Researchers at Sinai Hospital in Balti-


more are conducting two soon-to-be-pub- lished studies of point-of-care serology tests to aid in determining a patient’s immune status.37


be the easiest, fastest way to determine if someone needs a booster shot.37


The researchers say this testing may However,


research regarding this is still ongoing. Paul Gurbel, MD, Director of the Sinai Center for Thrombosis Research and Drug Develop- ment, stated that the tests can help doctors determine which patients might need a booster and when they would need it.38 The presence of neutralizing antibod- ies post exposure or vaccination indicates protection from infection; however, cut-off levels for neutralizing antibodies have yet to be determined.9


It is conceivable that using serology tests at the point of care REFERENCES:


1. Amanat F, Stadlbauer D, Strohmeier S, et al. A serological assay to detect SARS-CoV-2 serocon- version in humans. Nat Med. 2020;26(7):1033-1036. doi:10.1038/s41591-020-0913-5.


2. Wajnberg A, Amanat F, Firpo A, et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020;370(6521):1227- 1230. doi:10.1126/science.abd7728.


3. Zhang Yongchen, Han Shen, Xinning Wang, Xudong Shi, Yang Li, Jiawei Yan, Yuxin Chen & Bing Gu (2020) Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients, Emerg- ing Microbes & Infections, 9:1, 833-836, DOI: 10.1080/22221751.2020.1756699.


4. Long QX, Tang XJ, Shi QL, et al. Clinical and immu- nological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020;26(8):1200-1204. doi:10.1038/ s41591-020-0965-6.


5. Patricia Kaaijk, Verónica Olivo Pimentel, Maarten E. Emmelot, Martien Poelen, et al. Children and adults with mild COVID-19 symptoms develop memory T cell immunity to SARS-CoV-2 medRxiv 2021.09.10.21263333. doi: https://doi.org/10.1101/20 21.09.10.21263333.


6. Seow J, Graham C, Merrick B, et al. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat Microbiol. 2020;5(12):1598- 1607. doi:10.1038/s41564-020-00813-8.


7. Kellam P, Barclay W. The dynamics of humoral immune responses following SARS-CoV-2 infec- tion and the potential for reinfection. J Gen Virol. 2020;101(8):791-797. doi: 10.1099/jgv.0.001439..


8. Ramachandran T, Chattopadhyay S, et al. Longi- tudinal serology of SARS-CoV-2-infected individu- als in India: A prospective cohort study. Am J Trop Med Hyg. 2021 May 18;105(1):66-72. doi: 10.4269/ ajtmh.21-0164.


9. Ong D, Fragkou P, Schweitzer V, et al. How to


could identify individuals with inadequate immune responses to vaccination or infec- tion to help inform whether to administer a vaccine or booster. However, more studies are required to establish clinical utility.


Summary Currently, only tests authorized for use by the FDA should be used for clinical di- agnostic purposes. SARS-CoV-2 Ab tests with the highest sensitivity and specificity are preferred.21


To maximize the clinical


utility and full potential of SARS-CoV-2 antibody testing, it is likely that methods will need to be capable of rendering a quantitative test result, detect antibodies that are capable of conferring immunity (ex. neutralizing antibodies), and, most importantly, results must correlate with clinical outcome studies. In context, SARS -CoV-2 Ab tests have the potential to one day aid in identifying the presence or absence antibodies to indicate when therapies and vaccines are administered, and to effectively assess an individual’s immunity status.


interpret and use COVID-19 serology and immunol- ogy tests. Clin Microbiol Infect. 2021;27(7):981-986. doi:10.1016/j.cmi.2021.05.001.


10. Guo L, Ren L, Yang S, Xiao M, et al, Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis. 2020; 71(15): 778–785. doi: 10.1093/cid/ciaa310.


11. Ma H, Zeng W, He H. et al. Serum IgA, IgM, and IgG responses in COVID-19. Cell Mol Immunol. 2020. 17(7):773–775. doi: 10.1038/s41423-020-0474-z.


12. Beaudoin-Bussières G, Laumaea A, Anand SP, et al. Decline of humoral responses against SARS- CoV-2 Spike in convalescent individuals. mBio. 2020;11(5):e02590-20. doi:10.1128/mBio.02590-20.


13. Crawford et al. Dynamics of neutralizing anti- body titers in the months after severe acute respi- ratory syndrome coronavirus 2 infection. J Infect Dis. 2021;223(2):197-205. doi: 10.1093/infdis/jiaa618.


14. Johnson and Johson. Janssen COVID-19 Vaccine Package Insert. https://www.janssenco- vid19vaccine.com/hcp/covid19-resources.html. Revised August 27, 2021. Accessed October 29, 2021.


15. Moderna. Moderna COVID-19 Vaccine Package Insert. https://www.modernatx.com/ covid19vaccine-eua/providers/. Revised August 27, 2021. Accessed October 29, 2021.


16. Pfizer. Pfizer-Biontech COVID-19 Vaccine Package Insert. https://www.pfizer.com/products/ product-detail/pfizer-biontech-covid-19-vaccine. Revised September 22, 2021. Accessed October 29, 2021.


17. Wang X, Guo X, Xin Q, et al. Neutralizing anti- body responses to severe acute respiratory syn- drome Coronavirus 2 in coronavirus disease 2019 inpatients and convalescent patients. Clin Infect Dis. 2020;71(10):2688-2694. doi:10.1093/cid/ciaa721.


18. Simonovich VA, Burgos Pratx LD, Scibona P, et al. A randomized trial of convalescent plasma in Covid-19 severe pneumonia. N Engl J Med. 2021;384(7):619-629. doi:10.1056/NEJMoa2031304.


19. Chau, C.H., Strope, J.D. and Figg, W.D. (2020), COVID-19 Clinical diagnostics and testing technol- ogy. Pharmacotherapy. 2020 Aug;40(8):857-868. doi: 10.1002/phar.2439.


20. Hanson KE, Caliendo AM, Arias CA, Englund JA, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing. Infectious Diseases Society of America 2020; Version 1.0.0. https://www.idsociety.org/ practice-guideline/covid-19-guideline-serology/. Accessed August 10, 2021.


21. Centers for Disease Control and Prevention. Interim guidelines for COVID-19 antibody testing. https://www.cdc.gov/coronavirus/2019-ncov/lab/ resources/antibody-tests-guidelines.html. Updated September 21, 2021. Accessed October 13, 2021.


22. U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA authorizes first test that detects neutralizing antibodies from recent or prior SARS-CoV-2 infection. https://www.fda.gov/ news-events/press-announcements/coronavirus- covid-19-update-fda-authorizes-first-test-detects- neutralizing-antibodies-recent-or. Updated Novem- ber 6, 2020. Accessed October 13, 2021.


23. U.S. Food and Drug Administration. In vitro Diagnostics EUAs. FDA- Serology Template for Test Developers. https://www.fda.gov/medical-devices/ coronavirus-disease-2019-covid-19-emergency- use-authorizations-medical-devices/in-vitro- diagnostics-euas. Accessed: October 13, 2021.


24. U.S. Food and Drug Administration. In MLO-ONLINE.COM DECEMBER 2021 13


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54