Correlates of Protection: A Roadmap to Approach State Reopening

By Shivan Lala | The information in this post has been updated as of May 21, 2020

As state governments begin reopening businesses and public areas, public health officials have emphasized the importance of comprehensive testing before such actions can be taken. For many, “comprehensive testing” refers to the availability of SARS-CoV-2 antibody tests, which allows an individual to know if they were exposed to the virus that causes COVID-19. However, the antibody test may be an inaccurate measure of protective immunity against the virus, creating the need for more defined correlates of protection before full state reopening can be considered.

Correlates of protection are quantifiable, objective immune parameters that demonstrate protection against an infectious pathogen (1). While the currently available antibody tests determine exposure to SARS-CoV-2, the specific readout (IgG levels) does not provide any information on if the individual is protected – a key consideration in approaching state reopening. Measuring an individual’s IgG levels alone only shows the total amount of antibody produced, without testing the ability of said antibody to effectively neutralize the virus. While the IgG test is a useful diagnostic tool, state governments should focus on defining correlates of protection to inform their decisions.

Luckily, we can turn to both emerging COVID research and previous infectious disease research to more explicitly define these parameters. A preprint review of 18 coronavirus infection studies provides more specific definitions of immunological protection (2), including counts of various antibody types and experiments that test the ability of antibodies to neutralize the virus. Similar parameters were defined during the Ebola outbreak of 2014, which defined many mechanistic and non-mechanistic correlates of protection, such as virus-specific T cell count, blood RNA analysis, and innate lymphocyte count (3) – all of which provide a more robust view of an individual’s immune response beyond simple recognition of a pathogen.

As state governments develop reopening strategies, correlates of protection beyond serum IgG count must be considered. Efforts should be made to ensure testing focuses on functionally relevant immune parameters, which will provide the safest timetable for state reopening. While this process is more time consuming, it is paramount to ensuring the health of state populations and state economies, mitigating the effects of a potential “second wave” (4) of SARS-CoV-2 infection. By making the effort to provide robust testing, governments can build a more accurate and safe roadmap to approach their reopening efforts.

A common theme among countries beginning to reopen is vigorous testing – New Zealand, for example, has expanded its testing criteria to include a variety of lab tests, including RT-PCR and SARS-CoV-2 sequencing (5). However, New Zealand still relies on IgG testing as its primary diagnostic tool, a strategy paralleled by countries like Germany (6) that are starting to lift restrictions on businesses and public places. While testing in New Zealand and Germany did not rely on expanded correlates of protection, these countries quickly enacted thorough testing and prevention policies, allowing them to begin reopening. In comparison, the United States response has been significantly slower and less effective, creating the need to expand testing parameters beyond IgG. While it may be too late to follow the example set by New Zealand and Germany, defining concrete indicators of protective immunity represents the most safe and time-efficient path to state reopening.


1. Altmann, D. M., Douek, D. C. & Boyton, R. J. Comment What policy makers need to know about COVID-19 protective immunity. Lancet 6736, 19–21 (2020).

2. Huang, A. T. et al. A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. medRxiv (2020) doi:10.1101/2020.04.14.20065771.

3. Medaglini, D., Santoro, F. & Siegrist, C. A. Correlates of vaccine-induced protective immunity against Ebola virus disease. Seminars in Immunology vol. 39 65–72 (2018).

4. Lipsitch, M. Predicting the COVID-19 Pandemic | Coronavirus (COVID19) | JN Learning | AMA Ed Hub. AMA Ed Hub (2020).

5. New Zealand Ministry of Health. COVID-19 case definitions. (2020).

6. Bennhold, K. With Broad, Random Tests for Antibodies, Germany Seeks Path Out of Lockdown - The New York Times. The New York Times (2020).


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