Doctors: Should you antibody test?
As the COVID-19 pandemic rolls on and increased wide-spread testing becomes available nationwide, antibody tests will become widely available at testing sites, urgent cares, and emergency rooms. Should you provide these tests for your patients ? What information will they provide? Are they worth doing? Here are some things to consider.
First, it is important to understand that antibody (serology) tests are not stand-alone diagnostic tests! If an individual starts having a fever and cough, and runs over to the nearest drive-up testing site that only offers antibody testing, this individual would need to drive away and find a site that offers nasal swabs (molecular tests). With that being said, the viral nasal swab PCR tests, which are the diagnostic “Gold Standard”, may have up to a 20-50% false negative rate. This means that 1 in 5 individuals who truly have the disease are not caught by these nasal swab tests, according to a Johns Hopkins meta-analysis.
If an antibody test with high sensitivity is run concurrently with a viral test, a positive IgM/IgG antibody test would suggest a recent onset coronavirus infection, and can be positive as early as a day post symptom onset in some patients. This may provide for greater confidence that a negative nasal swab test result is truly negative versus a false negative, even in the acute phase of disease, helping to identify those individuals with disease whom otherwise would think they are virus-free and continue to spread disease.
Even antibody tests with the highest sensitivity would miss some patients who have disease as antibody titers within the first week may be too low to detect with point-of care antibody tests in some patients, but not all. A clinician should use their best judgment based on the patient medical history and physical exam to determine, in the acute setting, whether or not they need to draw any blood for labs, including a serology test.
If a patient is greater than seven days out from symptom onset, it is important to know that at this point, the accuracy of nasal swabs has declined even more, and that the amount of antibodies have increased in the blood, so it would be important to administer both the nasal swab and an antibody test. If a patient is more than two weeks out from symptom onset, in most patients an antibody test alone would allow you to determine whether they have had COVID-19 except for in those who are immunocompromised or have an immune disorder. Administering a nasal swab test will have a very high rate of false negatives, much higher than an antibody test.
Antibody tests also help to identify those who are asymptomatic, as well as those who are symptomatic but never get tested due to mild symptoms. A recent epidemiological study from Spain showed that 1/3 of the greater than 61,000 cohort in their study were asymptomatic and almost 20% of those who were symptomatic never received testing. Seroprevalence studies here in the U.S. have similar findings with one study in California showing that the reported number of cases is as much as 55-fold lower than the actual number of infections.
Why is this important? In order to understand how deadly this new disease is, the infectious fatality rate (IFR) must be known. That is, the proportion of infected people who will die as a result of this disease, including those who don't get tested due to mild or no symptoms. If those detected are a smaller proportion than those actually infected, our infectious mortality rate will be much higher than truly expected. This would give false implications of the scale of this pandemic and skew the responses of governments and individuals towards overreaction nationwide, which could cause tremendous physical and mental harms from the overuse of public health interventions like lockdowns and social distancing, as well as cause extreme financial and economic strain. On the other hand if the IFR is calculated too low, this could lead governments and individuals to under-react, causing increased loss of lives and overburdening of our hospitals and hospital staff. It is important to get the IFR right within your specific region and amongst varying demographics.
Finally, how will we truly understand the future relationship between SARS-CoV-2 antibodies and immunity from COVID-19 reinfection if we miss the majority of those infected initially? How likely is COVID-19 reinfection for people with and without detectable SARS-CoV-2 antibodies? This will be hard to accurately assess with many individuals remaining undetected for both disease and antibodies. As this pandemic rolls into later parts of the year, will a COVID-19 infection be a primary infection or a reinfection? If there are individuals truly being re-infected, what does this tell us about the possible efficacy of vaccinations? We don't have enough information from scientific studies to provide the answers to these questions, but once you know who has had COVID-19 within your patient population, you will be able to also know later whether it is a reinfection or a primary infection.
If there are enough reporting antibody test results, doctors will have the information they need within their communities, and will be better able to advise, educate, and advocate for their patients, communities, and government leaders. Active and passive surveillance are so important. We cannot wait until the pandemic is over to begin antibody testing or seroprevalence studies. Understanding COVID-19 disease transmission and deadliness is limited if our diagnostic testing is only able to find those with symptoms some of the time, those without symptoms probably even less of the time, and those who have had symptoms and won't get tested, ever. Antibody testing can help with detection within each of these groups.
References:
Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019
Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)
COVID-19 Antibody Seroprevalence in Santa Clara County, California
Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020
Clinical and Immunological Assessment of Asymptomatic SARS-COV-2 Infections
Contact Us for More Information
If you have any questions or would like more information about antibody testing or the antibody tests we supply, feel free to submit your information below and we’ll reach out to you.