Brief answer: No, not yet

Long explanation for brief answer:

We have all been following the news about COVID 19, learning of our success in “flattening the curve” and tentative plans to restart the economy. At this juncture, we need to know who has had the illness and probably has immunity and who remains at risk. We need to know our antibody status. After almost all viral illnesses, our immune system responds by producing antibodies, small proteins that specifically target the shapes of the viruses and can prevent future re-infection. Technologies for detecting antibodies such as enzyme-linked immunosorbent assay (ELISA) have been around for decades and can measure the quantity of antibodies in the blood. The first ELISA test for HIV came out in 1985. The rapid diagnostic tests (RDT) using flow immunoassays which provide a qualitative (present/not present) result have been around since the 1970’s. Given the existing diagnostic technologies, why don’t we have   reliable tests available for COVID 19 antibodies?

Earlier this year, the CDC made the disastrous decision to forgo a W.H.O RT-PCR test for COVID 19 and instead opted to develop its own. A series of delays and mistakes led to insufficient testing capabilities allowing the virus to spread unchecked. We are still hopelessly behind in our ability to test for active COVID 19 infection. I believe these failures have colored the Federal government’s approach to handling testing for COVID 19 antibodies. “Generals are always fighting the last war.”  If the original failure was over reliance on a central government lab, the current problem is failure to analyze and regulate an explosion of commercial products to ensure accuracy. There are now scores of rapid diagnostic tests being developed for COVID 19 antibody testing. As of this writing, only one RDT, a test by Cellex, has received FDA approval, at the more lax level of emergency use authorization EUA.  Analyzing the clinical performance data for the Cellex product, reveals some of the challenges in creating an accurate COVID 19 antibody test.

The package insert for the Cellex test describes a study using the blood from 128 RT-PCR documented COVID 19 patients (presumably in China), 90 who were in a quarantine facility and 28 more severely ill patients from a hospital. The test demonstrated an impressive 93.5% sensitivity, only 6.5% of infected patients were missed. Unfortunately, these patients are not representative of the population who would be tested in the United States, quite the opposite. We need the antibody studies to identify the asymptomatic and minimally symptomatic patients, who have never been PCR tested to document COVID 19 infection. Based on earlier antibody studies of other coronaviruses, such as MERS, evidence suggests that the overall amount of antibody produced correlates with the severity of illness, suggesting asymptomatic individuals may produce much less antibodies and be missed by a test designed to measure potentially higher levels generated from sick patients. How sensitive would the test be when utilized here in the USA? Who knows? That is a problem.

The Cellex package insert includes the disclaimer, “False positive results may occur due to cross-reacting antibodies form previous infections, such as other coronaviruses, or from other causes. “Other coronaviruses, include those causing the common cold, creating a serious false positive problem. Proposals for lifting the social distancing restrictions include identifying those with antibody evidence of past infection to be safely reintroduced into society at large. A person with a false positive antibody test could unknowingly infect others.

I predict that a successful antibody testing program will require validation with a large number of asymptomatic and minimally symptomatic patients, a case mix very different than used with currently manufactured tests. The NIH announced such a study on 4/10/20. https://www.nih.gov/news-events/news-releases/nih-begins-study-quantify-undetected-cases-coronavirus-infection. In addition to studying patients, I believe they are refining the test methodologies as well. To overcome the problem of false positive tests, we may need to employ a two-step process of testing, as we do for other viral infections such as HIV or hepatitis C. The first screening test has greater sensitivity but at the expense of less specificity. That is, in order not to miss any cases with the first test, you are willing to accept a higher false positive rate. The false positives can be further analyzed with a more specific test. In this case, a relatively simple lateral flow immunoassay (RDT) can screen for the presence of antibodies. Any positives could be further analyzed with an ELISA test which could measure quantitative titers against the COVID 19 virus, compared to quantitative titers of other coronaviruses, such as those for the common cold, potentially giving a more discriminating analysis  of COVID 19 antibody status.

Given the much higher level of complexity required for accurate COVID 19 antibody testing, I would recommend AGAINST being tested with any of the currently available tests. Unfortunately, we are just not there yet, a common refrain in my email updates.

I will continue to follow this issue closely and promise to notify you when we have access to an accurate test for COVID 19 antibody status.

Please contact me with any questions or concerns.

Thank you,

Barry Rotman, MD