What PCR Can—and Can’t—Tell Us About COVID-19: Understanding Ct Values and Contagion
PCR (Polymerase Chain Reaction) is a powerful tool used to detect genetic material, but it's often misunderstood when applied to diagnosing infectious diseases like COVID-19. To understand its limitations—and why a positive result doesn’t always mean someone is contagious—we first need to look at how PCR works and what the test results really mean.
What is PCR?
PCR was invented in 1983 by American biochemist Kary Mullis, who won the Nobel Prize in Chemistry for this revolutionary technique. It was originally designed as a laboratory tool to amplify tiny amounts of genetic material (DNA or RNA) so they could be studied in greater detail. PCR has transformed fields ranging from forensics to genetics to disease research.
It’s important to understand that PCR was not designed as a stand-alone diagnostic tool. Instead, it's best used to support clinical diagnosis by helping trained medical professionals detect whether a particular virus or bacteria’s genetic material is present in a sample.
How Does PCR Work?
PCR works by doubling the amount of targeted genetic material during each cycle. This process is exponential:
- 2 becomes 4
- 4 becomes 8
- 8 becomes 16
…and so on. After just 20 cycles, you have over a million copies of the original material. By 40 cycles, you have more than one trillion times the amount you started with.
To help visualize this, think of the legend of the chessboard and the grains of rice:
- If you place one grain of rice on the first square, and double it on each following square, by the time you reach the 40th square, the pile would weigh roughly 22,000 metric tons—about the weight of 220 fully loaded semi-trucks.
This is why the number of cycles—known as the cycle threshold (Ct)—matters.
- A test that detects viral material after 15 cycles likely found a high viral load.
- A test that needs 40 cycles may be detecting a tiny, possibly meaningless fragment.
Why Ct Values Matter
Research has shown that the higher the Ct value, the less likely it is that a person is still infectious:
- At a Ct of 25, about 70% of samples still contain live, culturable virus.
- At Ct 30, that drops to around 20%.
- At Ct 35 or higher, fewer than 3% of samples yield any live virus (Jaafar 2020; Singanayagam 2020).
- Findings from La Scola et al. (2020) further support this:
- All samples with Ct values between 13 and 17 led to positive viral cultures—meaning the virus could still replicate and potentially spread.
- Culture positivity declined steadily with higher Ct values.
- No live virus was recovered from samples with a Ct above 34.
These results strongly suggest:
- Ct values under 17 are closely linked with actual contagiousness.
- Ct values above 30–35 often reflect only leftover viral fragments that can no longer spread or cause disease.
· Key Takeaway:
PCR is a highly sensitive test—it can detect even the smallest traces of virus.
But only positive results with Ct values below 17 should be considered a strong sign of contagiousness.
Higher Ct values likely mean the person has recovered or was never contagious in the first place.
Real-World Evidence
These lab-based observations are backed up by real-world studies.
- A study involving 12,544 students at the University of Cambridge found that although some students tested PCR-positive, none were actually infectious upon further evaluation (Warne 2020).
- A court case in Portugal dealt with four German tourists who were quarantined after one tested positive. The Lisbon Court of Appeal ruled that a PCR test alone, especially at high Ct values, was not enough to justify quarantine, citing the unreliability of high-Ct results in determining infection status.
The Bigger Picture: Diagnosis vs. Detection
A key misunderstanding during the COVID-19 pandemic was assuming that a positive PCR test equals an active case of COVID-19. But that’s not how diagnosis works in medicine.
Here’s how a proper diagnosis is usually made:
- A doctor evaluates the patient’s symptoms, medical history, and overall condition.
- Tests like PCR are then used to support or confirm the clinical picture.
PCR detects genetic material. It does not tell us whether:
- The virus is alive,
- The person is still contagious,
- Or whether they are even sick.
What Should Be Done?
To improve how PCR testing is used and interpreted:
- Report Ct values alongside test results so doctors can assess their significance.
- Conduct follow-up viral cultures when contagiousness needs to be confirmed.
- Use clinical judgment—not PCR alone—to make decisions about quarantine, treatment, or public health responses.
Final Thoughts
PCR is a brilliant scientific tool—but like any tool, it must be used correctly and interpreted in context.
A positive PCR test result doesn’t necessarily mean someone is sick or contagious. It may simply mean that a small piece of viral material—possibly from an old or inactive infection—was detected. In that case, the test is working exactly as intended, but its result is being misinterpreted.
This is where cycle threshold (Ct) becomes essential:
- A result that turns positive before 17 cycles likely means the virus is still active and the person may be contagious.
- A result that turns positive only after 30–40 cycles probably means the virus is no longer active or transmissible.
Unfortunately, this nuance is often lost. As a result:
- Some people believe PCR is "fake" because they hear about false positives.
- Others believe PCR is always right and proves someone is dangerous just because they tested positive.
The truth is more balanced:
PCR is accurate at detecting genetic material—but it cannot tell us by itself whether someone is still infectious. That judgment requires context, medical expertise, and, ideally, additional testing.
To improve public understanding and guide better decisions, Ct values must be shared, and only low-Ct results (below 17) should be used to estimate whether someone is truly contagious.
By refining how we use PCR, we can avoid unnecessary fear and restrictions—while still protecting public health in a smarter, more targeted way.
References:
Jaafar, R., Aherfi, S., Wurtz, N., Grimaldier, C., Hoang, V.T., Colson, P., Raoult, D. and La Scola, B., 2020. Correlation between 3790 qPCR positives samples and positive cell cultures including 1941 SARS-CoV-2 isolates. Clin Infect Dis, p.ciaa1491. https://www.icpcovid.com/sites/default/files/2020-10/Correlation%20VL%20and%20cultivability.pdf?fbclid=IwAR2x6sHI8n4cE_f8Z7Vnh_oWlZAs8R0EXWc9JtSZiIGwvwHmLJT1vc9Koek
La Scola, B., Le Bideau, M., Andreani, J., Hoang, V.T., Grimaldier, C., Colson, P., Gautret, P. and Raoult, D., 2020. Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards. European Journal of Clinical Microbiology & Infectious Diseases, 39(6), p.1059. https://covid19-evidence.paho.org/handle/20.500.12663/920
Lisbon Regional Council of the Bar Association. 2020. Case number 1783/20.7T8PDL.L1-3, Habeas corpus, illegal detention, November 11, 2020. https://crlisboa.org/wp/juris/processo-n-o1783-20-7t8pdl-l1-3/
Warne, B. 2020. UoC Asymptomatic COVID-19 Screening Programme: Week 9 (30th November – 6th December 2020). Cambridge University.https://www.cam.ac.uk/sites/www.cam.ac.uk/files/documents/pooled_testing_report_30nov-6dec.pdf
Singanayagam, A., Patel, M., Charlett, A., Bernal, J.L., Saliba, V., Ellis, J., Ladhani, S., Zambon, M. and Gopal, R., 2020. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. https://pubmed.ncbi.nlm.nih.gov/32794447/