Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun 15;60(6):e0048221.
doi: 10.1128/jcm.00482-21. Epub 2022 Mar 7.

Immunity to SARS-CoV-2: What Do We Know and Should We Be Testing for It?

Anisha Misra  1 , Elitza S Theel  1
Affiliations
Review

Immunity to SARS-CoV-2: What Do We Know and Should We Be Testing for It?

Anisha Misra et al. J Clin Microbiol. .

Abstract

Preexisting immunity to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was nonexistent in humans, which coupled with high transmission rates of certain SARS-CoV-2 variants and limited vaccine uptake or availability, has collectively resulted in an ongoing global pandemic. The identification and establishment of one or multiple correlates of protection (CoP) against infectious pathogens is challenging, but beneficial from both the patient care and public health perspectives. Multiple studies have shown that neutralizing antibodies, whether generated following SARS-CoV-2 infection, vaccination, or a combination of both (i.e., hybrid immunity), as well as adaptive cellular immune responses, serve as CoPs for COVID-19. However, the diverse number and type of serologic assays, alongside the lack of cross-assay standardization and emergence of new SARS-CoV-2 variants with immune evasive characteristics, have collectively posed challenges to determining a robust CoP 'threshold' and for the routine utilization of these assays to document 'immunity,' as is commonly done for other vaccine preventable diseases. Here, we discuss what CoPs are, review our current understanding of infection-induced, vaccine-elicited and hybrid immunity to COVID-19 and summarize the current and potential future utility of SARS-CoV-2 serologic testing.

Keywords: COVID-19; SARS-CoV-2; antibodies; correlate of protection; serology; vaccines.

PubMed Disclaimer

Conflict of interest statement

The authors declare a conflict of interest. Elitza S. Theel is a consultant for Euroimmun US, Serimmune Inc., Oxford Immunotech and served on advisory boards for Roche Diagnostics.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, Subbarao K, Kent SJ, Triccas JA, Davenport MP. 2021. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 27:1205–1211. doi:10.1038/s41591-021-01377-8. - DOI - PubMed
    1. Gilbert PB, Montefiori DC, McDermott AB, Fong Y, Benkeser D, Deng W, Zhou H, Houchens CR, Martins K, Jayashankar L, Castellino F, Flach B, Lin BC, O’Connell S, McDanal C, Eaton A, Sarzotti-Kelsoe M, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi NS, Huynh C, Miller J, El Sahly HM, Baden LR, Baron M, De La Cruz L, Gay C, Kalams S, Kelley CF, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Carpp LN, Pajon R, Follmann D, Donis RO, Koup RA, Immune Assays Team section s . 2022. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science: 375:43–50. Moderna ITss. Coronavirus Vaccine Prevention Network/Coronavirus Efficacy Team section s. United States Government/Co VPNBTss. eab3435. doi:10.1126/science.abm3425. - DOI - PMC - PubMed
    1. Tacker DH, Bashleben C, Long TC, Theel ES, Knight V, Kadkhoda K, Rhoads DD, Linden MA, Fink SL. 2021. Interlaboratory agreement of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic assays in the expedited College of American Pathologists Proficiency Testing Program. Arch Pathol Lab Med 145:536–542. doi:10.5858/arpa.2020-0811-SA. - DOI - PMC - PubMed
    1. Theel ES, Johnson PW, Kunze KL, Wu L, Gorsh AP, Granger D, Roforth MM, Jerde CR, Lasho M, Andersen KJ, Murphy BM, Harring J, Lake DF, Svarovsky SA, Senefeld JW, Carter RE, Joyner MJ, Baumann NA, Mills JR. 2021. SARS-CoV-2 serologic assays dependent on dual-antigen binding demonstrate diverging kinetics relative to other antibody detection methods. J Clin Microbiol 59:e0123121. doi:10.1128/JCM.01231-21. - DOI - PMC - PubMed
    1. Saker K, Escuret V, Pitiot V, Massardier-Pilonchery A, Paul S, Mokdad B, Langlois-Jacques C, Rabilloud M, Goncalves D, Fabien N, Guibert N, Fassier JB, Bal A, Trouillet-Assant S, Trabaud MA. 2021. Evaluation of commercial anti-SARS-CoV-2 antibody assays and comparison of standardized titers in vaccinated healthcare workers. J Clin Microbiol:JCM0174621. - PMC - PubMed

Supplementary concepts