Summary

Serologic methods have been developed and will have important public health and clinical uses to monitor and respond to the COVID-19 pandemic.

Serologic assays for SARS-CoV-2 now have Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA), which has independently reviewed their performance.

Currently, there is no identified advantage of assays whether they test for IgG, IgM and IgG, or total antibody.

It is important to minimize false positive test results by choosing an assay with high specificity and by testing populations and individuals with an elevated likelihood of previous exposure to SARS-CoV-2. Alternatively, an orthogonal testing algorithm (i.e., employing two independent tests in sequence when the first test yields a positive result) can be used when the expected positive predictive value of a single test is low.

Antibodies most commonly become detectable 1-3 weeks after symptom onset, at which time evidence suggests that infectiousness likely is greatly decreased and that some degree of immunity from future infection has developed. However, additional data are needed before modifying public health recommendations based on serologic test results, including decisions on discontinuing physical distancing and using personal protective equipment.

Background

Serologic assays for SARS-CoV-2, now broadly available, can play an important role in understanding the virus’s epidemiology in the general population and identifying groups at higher risk for infection. Unlike viral direct detection methods such as nucleic acid amplification or antigen detection tests that can detect acutely infected persons, antibody tests help determine whether the individual being tested was ever infected—even if that person never showed symptoms. Serologic tests detect waning or past SARS-CoV-2 virus infection indirectly, by measuring the host humoral immune response to the virus. Therefore, serology assays do not typically replace direct detection methods as the primary tool for diagnosing an active SARS-CoV-2 infection, but they do have several important applications in monitoring and responding to the COVID-19 pandemic.

Although serologic tests should not be used at this time to determine if an individual is immune, these tests can help determine the proportion of a population previously infected with SARS-CoV-2 and provide information about populations that may be immune and potentially protected. Thus, demographic and geographic patterns of serologic test results can help determine which communities may have experienced a higher infection rate and therefore may have higher rates of herd immunity. In some instances, serologic test results may assist with identifying persons potentially infected with SARS-CoV-2 and determining who may qualify to donate blood that can be used to manufacture convalescent plasmaexternal icon as a possible treatment for those who are seriously ill from COVID-19.

Development of Antibodies and Immunity

Nearly all immune competent individuals will develop an immune response following SARS-CoV-2 infection. Like infections with other pathogens, SARS-CoV-2 infection elicits development of IgM and IgG antibodies, which are the most useful for assessing antibody response because little is known about IgA response in the blood.

Antibodies in some persons can be detected within the first week of illness onset. SARS-CoV-2 infections are somewhat unusual because IgM and IgG antibodies arise nearly simultaneously in serum within 2 to 3 weeks after illness onset. Thus, detection of IgM without IgG is uncommon. How long IgM and IgG antibodies remain detectable following infection is not known.

In addition, development of neutralizing antibodies can also be assessed. Neutralizing antibodies inhibit viral replication in vitro, and as with many infectious diseases, their presence correlates with immunity to future infection, at least temporarily.

Recurrence of COVID-19 illness appears to be very uncommon, suggesting that the presence of antibodies could confer at least short-term immunity to infection with SARS-CoV-2. Consistent with this observation, experimental primary infection in primates and subsequent development of antibodies resulted in protection from reinfection after the primates were rechallenged. Additionally, antibody development in humans correlates with a marked decrease in viral load in the respiratory tract. Taken together, these observations suggest that the presence of antibodies may decrease a person’s infectiousness and offer some level of protection from reinfection. However, definitive data are lacking, and it remains uncertain whether individuals with antibodies (neutralizing or total) are protected against reinfection with SARS-CoV-2, and if so, what concentration of antibodies is needed to confer protection.

Current Status of Antibody Testing in the United States

Antigenic targets

The two major antigenic targets of SARS-CoV-2 virus against which antibodies are detected are spike glycoprotein (S) and nucleocapsid phosphoprotein (N). While S protein is essential for virus entry and is present on the viral surface, N protein is the most abundantly expressed immunodominant protein that interacts with RNA. Multiple forms of S protein — full-length (S1+S2) or partial (S1 domain or receptor binding domain [RBD]) — are used as antigens. The protein target determines cross-reactivity and specificity because N is more conserved across coronaviruses than S, and within S, RBD is more conserved than S1 or full-length S.

Read more: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html