Until a vaccine is available, antibody tests may offer the best way to assess risk prevalence and community spread of COVID-19.
As cases of coronavirus disease 2019 (COVID-19) surge across the country, and the United States grapples with the prospect of a prolonged public health and economic crisis, leaders face urgent and difficult decisions about how to move our communities forward.
The hard truth is that short of an effective vaccine, returning to “normal” life must occur in a tiered approach and with careful consideration of the risks and benefits. These interim measures will depend on the ability of health care experts and community leaders to track and assess the risk and prevalence of community spread.
For this reason, Congress must prioritize—and states must utilize—funding for widescale implementation of antibody testing. Indeed, using highly accurate tests authorized by the FDA, antibody testing (or “serological testing”) has enormous potential to improve disease surveillance, a critical step to help enable effective policies to reopen society while minimizing unnecessary loss of life. These tests are also valuable in identifying potential donors of convalescent plasma, a therapy recently given emergency use authorization by the FDA for the treatment of hospitalized COVID-19 patients.
Time is of the essence here. Recent studies demonstrate that antibody levels wane over time and become undetectable in a significant proportion of patients. If we don’t act now and establish widespread antibody testing programs, the true spread of COVID-19 in different communities may never be fully understood.
Given the promise of antibody testing, it is unfortunate that the rapid proliferation of unreliable serological tests at the onset of the health crisis eroded public trust, created confusion about the value of antibody testing, and slowed some of the momentum around widescale adoption. It will therefore be critical going forward for clinicians, researchers, and public health leaders to understand the wide variation in accuracy among tests on the market today and to choose tests that provide the highest confidence in an accurate result.
What makes for an accurate test? A key factor is the test’s specificity. Specificity refers to the test’s ability to detect only what it is designed to detect—and nothing else. If the test is highly specific, there will be fewer false positives, or people who test positive for SARS-CoV-2 antibodies when they do not have them. Even seemingly small differences in specificity among available tests can put public health at significant risk. For example, a test with only 99% specificity means that at a disease prevalence of 1%, 1 in 2 positive results reported will be false.
Another key consideration is the antibody subtype the test is designed to detect. Various tests on the market today target SARS-CoV-2 antibodies for the nucleocapsid, or N protein. While antibodies for the N protein are easier to detect, they have little bearing on whether or not an individual has immunity from re-infection. That's why it's critical that assays target the Spike or S1 protein, which is the principal antigen through which the virus docks onto human cells and spreads infection.
Fortunately, and despite early hiccups, there are a handful of highly accurate tests on the market that are already helping public health officials better understand the magnitude of disease spread in the United States. Recently, the CDC, in partnership with public health labs, began using antibody tests to conduct largescale seroprevalence surveys that monitor disease spread. Preliminary results released in July found that in most of the 10 US sites under study, the number of past infections was likely “greater than 10 times more” than the number of reported COVID-19 cases. These and similar surveys, when conducted with highly accurate tests, can be enormously helpful in identifying regional hotspots and better understanding the true level of viral transmission.
Highly accurate antibody tests are also helpful in identifying donors for convalescent plasma therapy and aiding research into the development of treatments and vaccines. And while research is ongoing to confirm whether the SARS-CoV-2 antibodies detected by serologic tests confer a level of immunity against the virus, there are several reasons to be optimistic. Long-term immunity is the most commonly observed response in the vast majority of human viral infections, including similar coronaviruses which caused previous outbreaks. In addition, several labs have published the results of in-vitro studies that suggest COVID-19 antibodies have a neutralizing effect on the virus.
Harnessing the full potential of antibody testing will require funding and infrastructure. Therefore, it is imperative that Congressional leaders provide mechanisms for states to utilize high-quality antibody tests in data-driven efforts to protect the public health and get communities back on track. Lawmakers should heed recent calls from leading national healthcare advocates to ramp up testing by providing funding and support for the serologic tests that show the most accuracy and promise for our nation’s future.
While there are still many unknowns, there is consensus emerging that widespread antibody testing—using highly accurate tests—is a critical element to developing a more complete understanding of infection rates, immunity, potential treatments and vaccines, and ultimately, restarting the economy and our way of life. This is a weapon in the war on this virus we can ill afford to go without.
Fernando Chaves, MD, is a board-certified hematopathologistwho serves as Global Head of Medical and Scientific Affairs at Ortho Clinical Diagnostics.