Introduction:

Serology (antibody) tests for the SARS-CoV-2 virus have the potential to inform good public health decision making during the pandemic. This report describes potential uses of the tests, areas of uncertainty where additional research is needed, and examples from other countries now beginning to make use of these tests. The priority for the United States now is to make validated, accurate tests available to: (1) public health authorities, to conduct surveillance and to estimate the numbers of people previously infected. Should antibody tests be determined to correlate with immunity to the disease, they should then be made available to: (2) essential workers, with priority for healthcare workers and those who interact with vulnerable populations (eg, nursing home residents); and (3) individuals who may use them to assess their personal risk of becoming infected with SARS-CoV-2 (COVID-19 disease). These tests will be in high demand, and manufacturing should be scaled appropriately, but the first steps will be to ensure accuracy, validity, and comparability of available tests.

Serology testing (or equivalently, serological testing) for COVID-19 may be used to identify whether people were previously infected by SARS-CoV-2. This is important to determine, because the polymerase chain reaction (PCR) and other rapid diagnostic tests now being used identify the presence of viral material, which is found only in people who are currently infected. Not everyone who has had the disease has had the opportunity to be tested before the virus was cleared from their bodies, and as many as 25% or more people are asymptomatic.1,2 Thus, it is now presumed that there is a significant population in the United States who likely have been infected with SARS-CoV-2, have recovered, and currently possess some degree of immunity. Because public health decision making depends in part on an understanding of the disease prevalence and the prevalence of likely immunity, extensive antibody/serology testing is needed to determine the true prevalence of SARS-CoV-2. Individuals want to be tested not only for their own peace of mind, but also because a positive result (ie, a history of having been infected and cleared the virus) may theoretically release them from the constraints of public health physical distancing measures. However, it is not known whether the presence of antibodies correlates with protection from disease.

While serology testing has the potential to provide valuable information to individuals and to public health authorities, there are significant areas of uncertainty that will need to be addressed in the coming weeks and months. The first and most urgent is serology test validation. There are dozens of serology tests being marketed in the United States that are not providing accurate information and that are not comparable to each other.3 Ensuring that tests are comparable and accurate requires a validation process with access to many patient samples, overseen by the Food and Drug Administration (FDA). While such a validation process is apparently under way, it is unclear when it will be completed. Second, while some degree of immunity to COVID-19 after recovery is assumed by most experts, determining whether there is a specific antibody level that correlates with immunity will require additional research. Third, even if protective immunity is successfully induced by infection, it is not clear how long that immunity lasts. For SARS in 2003, antibodies were maintained in recovered patients for up to 2 years, but as the virus disappeared by mid-2004, protection from reinfection was never demonstrated.4

Because of the potential for relaxing physical distancing measures for those who have recovered, several governments and large employers are currently exploring the possible use of what has been termed “immunity certificates,” to release recovered people from physical distancing measures. Given the inaccuracies in available tests and the uncertainty about how the test results correlate to immunity, this is not a justifiable step at this time. In this report, we describe considerations surrounding the use of certificates, once accurate tests are available and validated and if they are correlated with immunity. A standard for COVID-19 immunity before a vaccine is available would need to be carefully constructed and monitored so as not to create perverse incentives. For instance, some people might imprudently try to get infected to evade physical distancing measures or to be hired by businesses that require immunity as a condition for employment. We address some of the ethical and legal implications of immunity certificates.

Serology tests will be an important tool for public health workers to estimate the prevalence of disease. These tests will be in high demand by individuals who hope to assess their risks of immunity to SARS-CoV-2. Serology testing, among other nonpharmaceutical interventions, can help to bridge the time before a vaccine is available. However, validated, accurate tests are currently in short supply. In this report, we seek to draw attention to the options for expanding access so that the potential benefits of serology tests can be realized as soon as practicable.