RECLAMACION: “Dr. Anthony Fauci appeared to acknowledge that large numbers of positive COVID-19 cases may arise from oversensitive tests that pick up mere fragments of the virus rather than active, viable infections. If true, many patients may have been receiving false-positive test results — causing much needless anxiety and disruption to everyday life — while the numbers of COVID-19 cases reported by public health authorities and major COVID tracking websites could be vastly overstated.”
REVIEW
An article published by Just the News on 8 November 2020 claims that, “many patients may have been receiving false-positive test results” and, “the numbers of COVID-19 cases reported by public health authorities and major COVID tracking websites could be vastly overstated.” To support these claims, the article cites statements made by Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, during a 16 July 2020 science podcast hosted by Vincent Racaniello, a virologist and professor at Columbia University.
The podcast discussed COVID-19 testing and the value of the PCR test to inform tested individuals about what measures they should take. The PCR test detects the presence of the virus by amplifying a small part of the virus’ genetic material. The number of amplification cycles needed to arrive at a level considered to be a “positive” result is also called the cycle threshold (Ct) value.
The Ct value depends on the quantity of virus in a sample. The more virus present, the fewer amplification cycles are needed to reach the level for a positive result, while a low viral load requires more amplification cycles to reach that same level. Whether one has a high or low Ct determines whether contact tracing and self-isolation measures would be useful. This is because high viral load (low Ct value) likely indicates that a person is infectious, whereas a low viral load (high Ct value) likely indicates that a person is not infectious or has low transmissibility. The video below, produced by Cold Spring Harbor Laboratory, provides a simple explanation of how PCR works in COVID-19 testing.
During the podcast, Fauci pointed out the issue of positive PCR tests with high Ct values, namely that many people with such results may no longer be infectious. This issue calls into question whether PCR tests are a practical way of informing a person infected with COVID-19 of what steps they should take after their diagnosis, specifically whether they are contagious and should self-isolate. This consideration is also relevant to helping public health authorities determine whether contact tracing for that individual is needed.
Other experts also expressed these concerns, as reported in this New York Times article. Michael Mina, an epidemiologist and assistant professor at the Harvard T.H. Chan School of Public Health, explained in the article that relying solely on the PCR test to inform individuals tested for COVID-19 of what steps they need to take next can be unreliable. This is because of the high number of infections in the U.S. and the amount of time the PCR test takes to return a result:
“People infected with the virus are most infectious from a day or two before symptoms appear till about five days after. But at the current testing rates, ‘you’re not going to be doing it frequently enough to have any chance of really capturing somebody in that window,’ Dr. Mina added.
Highly sensitive PCR tests seemed like the best option for tracking the coronavirus at the start of the pandemic. But for the outbreaks raging now, he said, what’s needed are coronavirus tests that are fast, cheap and abundant enough to frequently test everyone who needs it — even if the tests are less sensitive.”
However, several outlets, including Just the News, incorrectly interpreted this information to suggest that the PCR test’s high sensitivity is responsible for inflating the number of COVID-19 cases reported in the U.S. and that the true number of infections is smaller than reported figures indicate. This inaccurate interpretation circulated in September 2020 and is based on the aforementioned New York Times article, which Just the News also cites. Health Feedback reviewed the claim previously and found it contained flawed reasoning.
As explained in the previous review, this claim fails to distinguish between the test’s ability to confirm a COVID-19 infection—which is what case numbers measure—with the test’s ability to determine contagiousness, which is the key issue that both the podcast and the New York Times article address. The two categories are distinct. For instance, recovering (convalescent) COVID-19 patients can still test positive for a certain period of time, as documented by South Korea’s Center for Disease Control. This is because the PCR test cannot distinguish between infectious and “dead” (non-infectious) virus.
The New York Times article also states that in recovering patients, “Tests with thresholds so high may detect not just live virus but also genetic fragments, leftovers from infection that pose no particular risk.” Fauci also refers to such patients with the statement, “So, I think if somebody does come in with [a Ct value of] 37, 38, even 36, you got to say, you know, it’s just dead nucleotides, period.” According to the New York Times article, “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.” However, experts who were interviewed found this to be too high, and that a better cutoff for a positive result would be between 30 and 35, or even less.
Alternatively, the New York Times article also points out that low viral loads can be detected by PCR tests of people who are in the early stages of infection, “The F.D.A. noted that people may have a low viral load when they are newly infected. A test with less sensitivity would miss these infections.” But these people could become infectious later when viral load increases as the infection progresses.
It is inaccurate to label these high Ct positive results as “false positives”. The term “false positive” indicates that a person tested positive but does not have the disease[1]. However, a person who is or has been infected if they test positive, regardless of whether the test had a high or low Ct value. This also means that it is appropriate to consider a person with a positive result and high Ct value as a COVID-19 case.
Therefore, the sensitivity of the PCR test is not responsible for the high number of COVID-19 cases in the U.S. Simply put, COVID-19 case numbers are high because there are many infected people. This indicates a high level of virus transmission in the community and public health measures, such as physical distancing and lockdowns, are effective and important for reducing the number of COVID-19 infections and protecting the community[2,3].
Apoorva Mandavilli, the journalist who wrote the New York Times article, also stressed this point in a Twitter thread, clarifying that “people who test positive but with high CTs *were* contagious, just at an earlier time point. They are not contagious *anymore*. Doesn’t mean they were never infected, so doesn’t affect the case count.”
To those who are twisting the PCR article to think this is why US numbers are lower: a big NOPE. People who test positive on the PCR are infected, they just may not be infectious.
— Apoorva Mandavilli (@apoorva_nyc) September 3, 2020
In summary, the claim that the COVID-19 case counts in the U.S. are inflated because of the PCR test’s sensitivity is based on an inaccurate and misleading conflation of contagiousness with the presence of infection. Both the podcast and the New York Times report highlight concerns about whether PCR test results are of practical use in determining if a person is contagious, which has implications for the necessity of contact tracing and self-isolation. The article and podcast also note a potentially large proportion of positive results from PCR testing for COVID-19 occur in people with low viral loads who are unlikely to be contagious.
But the podcast and the report do NOT say that people with positive test results and high Ct values were wrongly diagnosed as COVID-19 cases. Regardless of whether the Ct value is high or low, a positive test indicates that the person is or has been infected with the virus, which qualifies them as a COVID-19 case.
In short, the high number of COVID-19 cases observed in the U.S. is due to a high number of infected people in the community, not the PCR test’s sensitivity. Hence public health measures, such as physical distancing and lockdowns, are important for reducing the rate of infection in the community. Given testing bottlenecks in the U.S., the number of COVID-19 cases is much more likely to be underestimated, rather than overestimated as these videos and articles claim.
REFERENCES
- 1 – Lalkhen et al. (2020) Clinical tests: sensitivity and specificity. Continuing Education in Anaesthesia Critical Care & Pain.
- 2 – Flaxman et al. (2020) Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe. Nature.
- 3 – Hsiang et al. (2020) The effect of large-scale anti-contagion policies on the COVID-19 pandemic. Nature.
