A number of pharmaceutical companies are rushing to market COVID-19 antibody tests in the hope that a sufficient number of Americans can be tested for COVID-19 antibodies on the assumption that these antibodies provide partial or total immunity from contracting COVID-19 again.
There are a number of problems with this assumption. First, Coronaviruses are a large family of enveloped RNA viruses which include severe acute respiratory syndrome (SARS) (2002), Middle East respiratory syndrome (MERS) (2012), or coronavirus disease 19 (COVID-19) (2019). To date, there are no known treatments and no vaccine for these RNA viruses. How do SARS and MERS compare with COVID-19?
These RNA viruses have not proven readily susceptible to the development of a vaccine, so the repeated public assertions that a vaccine may be available in as soon as 18 months is just false hope happy talk. (The mumps vaccine—considered the fastest ever approved—took four years to develop and adequately test for safety before approval for use).
Second, some of the COVID-19 antibody tests being rushed to market are of dubious quality or have not been properly calibrated, as many infectious disease experts have been warning us. These tests are producing a high rate of false-positive or false-negative results.
Dr. Allan Detsky, professor of Health Policy, Management and Evaluation and Medicine at the University of Toronto (He was physician-in-chief at Toronto’s Mount Sinai Hospital during the SARS outbreak of 2003), and Dr. Isaac Bogoch, an infectious disease physician and scientist at Toronto General Hospital, and associate professor of Medicine at the University of Toronto explain Why coronavirus antibody test will not be a panacea:
In the course of most infections, people’s immune systems produce antibodies. For some, but not all, viruses the presence of those antibodies indicates partial or full immunity from reinfection.
The hope is that if we could test everyone’s blood for antibodies, it would tell us who can safely return to work and to social activities and who needs to remain protected. But the utility of such tests depends on two assumptions: The first is that the presence of antibodies grants immunity to infection [see below], and the second is that when an antibody test is positive, it truly means the person has antibodies in their blood.
‘False positive’ tests
In a setting where the prevalence of a disease like COVID-19 is small, then even with serologic tests that are very specific (but falling just short of 100%), many people who have a positive test will not actually have the antibodies. These are termed “false positive” tests.
If those with false positive tests (and no antibody protection) reintegrate, they won’t be safe from acquiring COVID-19. For example, let’s say a test 90% accurate (which is deemed to be pretty accurate in many clinical scenarios) is deployed in a setting where COVID-19 prevalence is only 1%, which in American today would be about 3 million people.
In this setting, assuming every person was tested, 30 million Americans would receive positive results, and of those positive results 27 million would be false positives.
While it seems counterintuitive that a positive result from a test deemed accurate leads to so many false positives, it is because even the slightest degree of misspecification is magnified by the fact that almost no one in the population really has antibodies. The only way to negate the low prevalence is to have a specificity of 100%, which is usually difficult to achieve.
Why serologic test is not useful for now
The question is: What is the actual prevalence of recovery from COVID-19 in the population? If we look at the United States as a whole, as of April 18, there were about 700,000 documented [confirmed] cases, most of whom will recover. We know that this is a drastic underestimate of the true number of cases, but even if it is 10 times larger, the total number is 7 million.
There are 328 million people in the USA, so the prevalence would be 2.1%. With a rate of false positives at 10% or greater, these serologic tests are not as helpful as we would like them to be.
Of course, the prevalence is not uniform across America and Canada. In New York City, the prevalence might be as high as 15-20%, in which case serology will be more useful. But in Montana, the prevalence at this time is likely well below 1%, making the tests not as useful there.
What do we do?
First, to be useful, COVID-19 antibody tests will have to demonstrate that they are extremely specific — in the range of 99% or higher. Some serology tests are performed in laboratories, while others are being marketed for point-of-care use at home or in doctors’ offices. It is likely that the former will have greater specificity and more meaningful results compared with the latter.
Second, for most of the USA at the present time, COVID-19 serology will not be useful for individual counseling. This situation will change as the prevalence of infection grows, but that will take many months.
Rushing point-of-care tests to market is a mistake until we can document and validate that they are very close to 100% specific. And when they are used, the results must be interpreted in the context of the prevalence of prior COVID-19 infection in those communities and settings.
Finally, the assumption that the presence of antibodies grants immunity to infection is now in doubt. WHO Warns You May Catch Coronavirus More Than Once:
Catching Covid-19 once may not protect you from getting it again, according to the World Health Organization, a finding that could jeopardize efforts to allow people to return to work after recovering from the virus.
“There is currently no evidence that people who have recovered from Covid-19 and have antibodies are protected from a second infection,” the United Nations agency said in an April 24 statement.
The WHO guidance came after some governments suggested that people who have antibodies to the coronavirus could be issued an “immunity passport” or “risk-free certificate” that would allow them to travel or return to work, based on the assumption that they were safe from re-infection, according to the statement. People issued such a certificate could ignore public-health guidance, increasing the risk of the disease spreading further.
Chile was the first country to announce plans to issue immunity cards based partly on antibody tests. This has raised concerns because the tests have proven unreliable elsewhere, and some people may get deliberately ill in order to obtain the card. The U.S. and others have nonetheless said they’re looking into the option.
While there’s a consensus that the key to ending the coronavirus pandemic is establishing co-called herd immunity, there are many unknowns. One is whether researchers can develop a safe and effective vaccine. Another is how long people who’ve recovered have immunity; reinfection after months or years is common with other human coronaviruses. Finally, it’s not clear what percentage of people must be immune to protect the “herd.” That depends on the contagiousness of the virus.
The WHO said it’s reviewing the scientific evidence on antibody responses to coronavirus, but as yet no study has evaluated whether the presence of antibodies “confers immunity to subsequent infection by this virus in humans.” And while many countries are currently testing for antibodies, these studies aren’t designed to determine whether people recovered from the disease acquire immunity, the agency said.
All this “18 months” to a vaccine happy talk is just false hope. Unless and until there is a vaccine, we are going to have to come to terms with the new world in which we live. It may take a miracle of science to discover an effective vaccine for RNA viruses that have not proven readily susceptible to the development of a vaccine so far.
So when Vice President Pence demonstrates that he is just as ignorant as Donald Trump by claiming that The Coronavirus Outbreak Could Be Over by Memorial Day, the man is obviously high from huffing Lysol (as endorsed by his boss).
PSA: do not try this at home.
It is hard not to be reminded of T.S. Elliot’s poem “The Hollow Men” (1925), the last four lines of which are “probably the most quoted lines of any 20th-century poet writing in English”:
This is the way the world ends
This is the way the world ends
This is the way the world ends
Not with a bang but with a whimper.
Politico reports “Unreliable antibody tests flood the market as FDA waives quality reviews”, https://www.politico.com/news/2020/04/27/reliable-antibody-tests-coronavirus-207589
The Food and Drug Administration is dealing with a flood of inaccurate coronavirus antibody tests after it allowed more than 120 manufacturers and labs to bring the tests to market without an agency review.
Agency leaders have said they tried to create more flexibility for makers of antibody tests to help inform discussions about when people can safely return to work and school, and to identify survivors whose antibody-rich blood could help treat the sick.
But many of the tests available now aren’t accurate enough for such purposes. Some are giving too many false positive results, which could mislead some people into thinking they have already been infected.
Public health experts say the FDA shouldn’t have waived its reviews of antibody tests and are calling on it to crack down.
On Friday, the House Oversight Committee released a report on antibody testing that said “numerous companies appear to be marketing fraudulent tests” — and that the FDA had “failed to police the coronavirus serological antibody test market.”
The FDA formally warned health care providers April 17 of the concerns surrounding the bulk of the antibody tests available for sale, explaining that it “does not review the validation, or accuracy, data for these tests unless an EUA is submitted.”
The New England Journal of Medicine is a good resource, saying the same things as the WHO, and The Lancet summed things up perfectly;
“The coronavirus disease 2019 (COVID-19) crisis is a pandemic challenging human biology, the capacity of acute care hospitals, the financial resilience of economies, and the communication network for people.”
COVID-19 is here for the long haul, so we now face two dangers, the virus itself, and our reaction to the virus.
Liberals – “We need good, solid, peer reviewed science so that we can start figuring out what we can keep from our old lives and what we’ll need to change.”
Conservatives – “Let’s all go get tattoos!”