A COVID-19 test administrator assigned to the Mississippi Air National Guard talks to a patient at a mobile testing site for COVID-19 in Port Gibson, MS, April 22, 2020. Photo credit: The National Guard / Flickr (CC BY 2.0)

Until an effective coronavirus vaccine is developed, the only way of bringing the global COVID-19 pandemic under control is to identify infectious individuals and limit their movements before they can spread the virus. Doing that depends on accurate testing.  But especially in the United States, testing has proven problematic.  Laurence Kotlikoff wants you to know that we already possess technology that could change the course of the coronavirus pandemic.

Global Insights Magazine/Global Geneva is partnering with the Who,What,Why investigative newsportal to help broaden access to content, such as this version by Bethany Carlson (see original here), that we believe would benefit from broader global readership.

To date, however, the US Food and Drug Administration has refused to approve any test that can be processed outside a laboratory, and although a number of companies offer unapproved tests that can be collected at home, these usually cost upwards of $100 a piece and still need to be sent to a laboratory for analysis before the results can be known. That can take several days during which a virus carrier is likely to come in contact with dozens of other people, creating a new chain reaction of infection.  

Currently available tests, which are approved by the FDA, can prove to be extremely expensive, in some cases testing facilities charge as high as $1,000 per test, depending on which clinic orders the test.  The high cost of testing is likely to put any comprehensive testing programs beyond the reach of the budgets of most states in the US.  For third world governments, the high cost of testing can make an effective testing program economically impossible.

A test that could cost as little as 1-5 dollars…

Faced with this grim scenario, two university researchers think they may have a solution—if anyone will listen.  Dr. Michael Mina, an epidemiologist at Harvard’s T.H. Chan School of Public Health, and Laurence Kotlikoff, who teaches economics at Boston University, are promoting a test for COVID-19 that consists of antibody-coated strips of paper  which can detect the coronavirus when it comes into contact with an individual’s saliva. Their test could be produced for as little as $1 to $5, and could easily be sold over the counter and used at home daily, or even multiple times a day, to detect active infection and transmission of SARS-CoV-2 and to help individuals determine when they need to isolate to prevent spreading the coronavirus. “This is an answer,” Laurence Kotlikoff says. “This is the answer.”

According to Mina,  the tests could be produced in large quantities almost immediately because they could be made and distributed by almost any facility that makes paper. They already exist in prototype. Manufacturers are not producing them, however, because, under current guidelines, they are not likely to be approved for diagnostic use by the FDA

The current test used to detect coronavirus infection is the polymerase chain reaction (PCR) test, an extremely sensitive test that detects minute amounts of viral material in upper or lower respiratory specimens. According to Mina, there are myriad problems with this test as it is being utilized in the US. It is expensive. It is time-consuming. Perhaps most importantly, the test is so sensitive that it can detect even fragments of viral RNA, thereby diagnosing as “positive” individuals who are no longer actively transmitting the virus.

In fact, according to Mina, “the vast majority of PCR positive tests we currently collect in this country are actually finding people long after they have ceased to be infectious.”

Nine out of 10 people in the United States go undiagnosed

As Mina explained when he appeared as a guest on the podcast This Week in Virology, “We have created this whole ecosystem in which we are so focused on high-end, expensive tests that we are [effectively] not testing anyone because we are trying to use clinical grade tests. If you look at the CDC’s latest estimate, 9 out of 10 people go undiagnosed with this virus today in the US.”

Laurence Kotlikoff sees the current system as a classic example of the “perfect destroying the good.” 

“We have created this whole ecosystem,” he says, “in which we are so focused on high-end, expensive tests that we are [effectively] not testing anyone because we are trying to use clinical grade tests. If you look at the CDC’s latest estimate, 9 out of 10 people go undiagnosed with this virus today in the US.”

Late or overdiagnosis has serious consequences. In Massachusetts, for example, Mina explained on This Week in Virology, “the suggestion for contact tracing is to take people from the point that they were positive-sampled and ask them to think back two days; so we are essentially taking people who might be two weeks post-transmissability, and we are spending huge dollars to go and contact-trace people they were with over the last two days — it’s completely ridiculous.”

A huge — perhaps incalculable — amount of money has been spent and will be spent on this high-sensitivity testing. Based on the number of total tests conducted in the US (nearly 65.8 million as of August 11, at an average cost of $100), it seems likely that the US has already spent more than $6 billion on testing alone.

It is also unquestionably true that some facilities are profiting exorbitantly from serology and PCR coronavirus testing. ProPublica has reported on one clinic in Texas which charged $2,479, including a $1,784 “facility fee,” for administering a $175 COVID-19 antibody test to a child who did not even leave his parent’s car while being tested.

An inexpensive paper test would be, of necessity, less sensitive than the sort of test conducted within a lab, but Mina says that is beside the point. 

Infected people walking the streets as if flamethrowers

“Imagine you are a fire department and you want to make sure that you catch all the fires that are burning so you can put them out. You don’t want a test that’s going to detect every time somebody lights a match in their house — that would be crazy: you’d be driving everywhere and having absolutely no effect. You want a test that can detect every time somebody is walking the streets with a flame-thrower.” 

Patients with a high viral load in their respiratory secretions — some of whom may not yet even be symptomatic — are the ones “walking the streets with a flame-thrower.” Samples collected from these patients contain, according to Mina, millions, billions, or even trillions of copies of the virus per milliliter, a concentration easily detected by paper tests. These “floridly positive” patients are the ones who must isolate themselves to halt the spread of the virus.

Extremely sensitive tests are not only more expensive and difficult to produce, but they may be counterproductive insofar as they fail to distinguish between individuals who are transmitting virus and those who are recovering from infection but no longer contagious. Furthermore, due to the difficulty of accessing testing and the backlog in processing, Kotlikoff estimates that less than 3 percent of actively infected people are being diagnosed by PCR tests in time to take steps to avoid infecting others.

“The PCR test,” Kotlikoff explained, “is generating false positives all the time. [It] is not a perfect test, but somehow is being held up as the gold standard; well, it’s the gold standard that nobody is using and it’s totally ineffectual and it’s too expensive and it’s too slow — it’s a worthless test at this point. So we’re holding up something that is worthwhile and could save the day to meet the standard of something that is worthless.” 

In the United States, as long as the FDA applies the same high sensitivity standards to rapid paper tests as they do to diagnostic tests conducted in labs, manufacturers will not produce the test due to “regulatory risk;” under current guidelines, to do so would be illegal. The paper tests could theoretically be recategorized as “surveillance” tests that would be held to a lower standard of sensitivity, but there is, in fact, as Jonathan Shaw recently reported, “no alternative regulatory process for tests designed to ensure population-level wellness — such as a certification program that might be run through the Centers for Disease Control.”

“Not everybody is going to comply,” Kotlikoff said, “but people that don’t comply will be kept alive by the people who do comply.”

A dire failure: The government needs to take the right steps

The FDA could address this problem by communicating its willingness to work with manufacturers to approve at-home coronavirus tests — or at the very least by transferring oversight to the US Centers for Disease Control.

If these agencies are not willing to take the necessary steps on their own, Kotlikoff argues, then the president himself should step in to recommend that they do.

This does not seem likely to happen. 

“What I have seen,” said Kotlikoff, “is that our government is chock full at this point of people who have no right to be in the position that they hold … every cabinet person is a political hack as far as I can tell.” These failures are not limited to the GOP, either: “The Democrats have equal culpability on this issue. Where is Schumer — has he not read the New York Times? Where are the people who are the intelligent leaders of the Senate? Where is Mitt Romney?”

For Mina and Kotlikoff, this unwillingness to address the crisis in coronavirus testing represents one more of many failures in the US government’s response to the virus.

“This entire pandemic,” said Mina, “from the US-centric perspective has just been defined by poor decision-making and poor leadership and taking away power where it should be placed in terms of appropriate responses and replacing it with people who don’t know what the hell they are doing.” 

Given the scope of the incompetence demonstrated by public officials’ response to the pandemic, the public must be empowered and educated to take responsibility for their own health and the health of their community; enabling the production and distribution of at-home tests for the virus is a crucial step in this direction.

Some have expressed ambivalence about at-home coronavirus testing, wondering, for example, whether patients can be trusted to appropriately quarantine after a positive test without surveillance and supervision. Indeed, one of the regulatory hurdles in the recently updated FDA guidelines is that even tests produced for at-home use must specify a method by which results will be reported to public health authorities.

Donald Thea, a professor of global health at Boston University, has worried that “providing home-based tests to individuals without a component of required reporting means missing potentially critical public health information.” 

Testing needs to be cheap, frequent and widely available

On July 29, the FDA released new guidelines mandating that over-the-counter at-home tests be at least 90 percent as sensitive as PCR tests and that prescription at-home tests be at least 80 percent as sensitive. In a statement to WhoWhatWhy, the FDA explained that these less sensitive prescription tests “are intended for use under the supervision of a healthcare professional” who would evaluate symptoms and encourage individuals to quarantine if they have received what might be a false negative result.

In requiring 80 percent rather than 90 percent accuracy for some rapid tests, Kotlikoff said, “the FDA is at least moving in the right direction.” Certainly, neither Kotlikoff nor Mina is suggesting that patients should be diagnosing and treating COVID-19 absent professional medical advice or that there should be any reduction in masking or social distancing.

“If a test is positive even once, notify your doctor. If it is positive three times, go have a deep nasal PCR test to confirm that you are positive,” Kotlikoff explained. “The public health concern of the FDA that somebody is positive but won’t get that confirmed, or that they think they are positive and they actually are not — well, that can be dealt with via instructions.”

No test will be perfect, and not everyone who uses the test will use it perfectly. This is a surmountable problem, however: “Not everybody is going to comply,” Kotlikoff said, “but people that don’t comply will be kept alive by the people who do comply.”

“If your goal is not to have a heavy hand over the population,” Mina explained, “this is the way to do it.”

Even if government officials wanted to “have a heavy hand over the population” — as would be required by another shutdown, and which would likely not go over well with the subset of Americans who are opposed even to wearing cotton masks — they do not seem to possess the resources or will to do so.

Do we have enough contact tracers to supervise grocery shoppers or backyard barbecues? Will working parents be willing or able to keep a child home from school for 10 days while they await the results of a PCR test which will tell them only that, as of 10 days before, their child did or did not have traces of coronavirus RNA in their nasal passages? Will police departments, in the wake of the George Floyd protests and calls across the country to reduce funding for law enforcement officers, be available to uniformly enforce mask mandates?

The answer to all these questions is clearly no.

Considering the wide variety of manifestations of the virus and the possibility of asymptomatic transmission, empowering individual Americans to protect themselves and their communities will absolutely require cheap, frequent, and widely available testing.

In a statement provided to WhoWhatWhy on August 11, the FDA reiterated the importance of high-sensitivity testing. However, they also said that they “support alternative proposals, including a strategy that involves serial testing using less sensitive tests to achieve performance when the available information demonstrates that the benefits outweigh the risks.”

“I view this as a very important, useful, and welcome statement by the FDA,” said Kotlikoff. “In my view, the benefits of rapid home testing with high, e.g., daily, frequency far outweigh the costs in a context in which sensitivity is 50 percent or higher and [the chance of a false positive] is 1 percent or lower.”

We have the technology to produce this type of test immediately and must do so; indeed, they may be our only hope to beat the pandemic.

Bethany Carlson is an editor at Who.What.Why (whowhatwhy.org) a US-based Internet publication.

For more on this topic, tune in to WhoWhatWhy’s podcast on Friday, August 14, to hear an interview with Dr. Michael Mina. 

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