02 September 2020

The New York Times: “Your Coronavirus Test is Positive. Maybe It Shouldn’t Be”

The PCR test amplifies genetic matter from the virus in cycles; the fewer cycles required, the greater the amount of virus, or viral load, in the sample. The greater the viral load, the more likely the patient is to be contagious.

This number of amplification cycles needed to find the virus, called the cycle threshold, is never included in the results sent to doctors and coronavirus patients, although it could tell them how infectious the patients are.

One solution would be to adjust the cycle threshold used now to decide that a patient is infected. Most tests set the limit at 40, a few at 37. This means that you are positive for the coronavirus if the test process required up to 40 cycles, or 37, to detect the virus.

Tests with thresholds so high may detect not just live virus but also genetic fragments, leftovers from infection that pose no particular risk — akin to finding a hair in a room long after a person has left, Dr. Mina said.

Apoorva Mandavilli

I saw this article on Twitter a couple of days ago and something didn’t feel quite right about it. At first look it seems to argue that PCR tests are too sensitive and therefore a positive result does not accurately reflect if the person is infected or not, casting doubt on months of testing and the policy of isolating asymptomatic patients. It is certainly the impression most people on Twitter were left with, judging by the replies and quote tweets. Reading it again, I noticed the author is regularly quoting one Dr. Mina, so I decided to dig a bit further into this reporting.

It didn’t take long to discover his Twitter profile and a long string of tweets trying to clarify the article above. He recommends repeating PCR tests when the results show low viral loads to see if these are increasing – pointing to a recent infection developing into illness – or stable/declining, indicating someone who is already recovering and most likely no longer contagious. This important point is mentioned only in passing in the article, in fact I noticed it only on my third read! How many people would take the time to research the original statements of the scientist and double-check the journalist’s work?

In the final tweet he directly contradicts the article’s talking point of reducing the cycle threshold, thereby missing large portions of infected people. It seems to me that the journalist has either misunderstood his message or willfully misstated it, leading with a clickbait title that is factually wrong: a positive PCR test does accurately reflect the presence of the virus, but further data is needed to make the correct decision regarding isolation and treatment.

The journalist’s tweet has since gone viral – it currently has 6.5K retweets, 1.9K quote tweets and 10.4K likes – while engagement with Dr. Mina’s thread is in the low hundreds. An unfortunate example how science communication, including in public health, can easily fail to transmit the correct message and instead ends up amplifying confusion and doubt among the public. Maybe that was not her intent, but when you have large amounts of people decrying health measures like isolation and social distancing, their first reaction reading this will be to further revolt against those measures and scientific advice, making it harder to control the pandemic.

As a side note I am constantly amazed that my own country seems to have better protocols than the Unites States. As far as I understand, current procedure is that people with positive results to a coronavirus PCR test are submitted to a second validation test the next day. The number of reconfirmed cases is roughly half of daily reported cases, possibly indicating that the rest are people with mild forms of the disease on the way to recovery. It is astonishing that the United States has not managed to organize something similar, or to deliver test results in around 24 hours.

Update: Christian Drosten, one of the leading German virologists, proposes a similar strategy for handling positive PCR tests in the future, but he refrains from putting forward a tolerance limit (translated from German by me):

Zusätzlich brauchen wir eine weitere entscheidende Änderung unserer Strategie: eine Testung auf Infektiosität statt auf Infektion. Die Information dafür liefern die gängigen PCR-Tests schon in Form der Viruslast. Eine niedrige Viruslast bedeutet, dass ein Patient nicht mehr ansteckend ist. Würden wir uns zutrauen, aus den inzwischen vorliegenden wissenschaftlichen Daten eine Toleranzschwelle der Viruslast abzuleiten, könnten Amtsärzte diejenigen sofort aus der Abklingzeit entlassen, deren Viruslast bereits unter die Schwelle gesunken ist. Es würden wohl die allermeisten sein.

In addition, we need another crucial change in our strategy: testing for infectivity instead of infection. Common PCR tests already provide the information for this in the form of the viral load. A low viral load means that a patient is no longer contagious. If we dared to derive a tolerance threshold for the viral load from the scientific data currently available, doctors could immediately discharge those whose viral load has already fallen below the threshold. It would probably be the vast majority.

Christian Drosten

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