PCR Testing - Credit CDC PHIL
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In Toxicology, the adage - credited to Paracelsus (1493-1541) - that "The dose makes the poison" is generally true. A lower dose of anything is usually less dangerous than a higher dose, although everything is toxic in high enough quantities.
While this can also hold true with viruses, some viral pathogens (Norovirus comes to mind) require extraordinary low dose to establish a foothold in a new host.
One of the reasons why the original SARS virus (which emerged in 2002-2003) was eventually contained and did not escalate into a pandemic was that it was less transmissible - particularly by asymptomatic carriers - than SARS-CoV-2.
We are still learning about the transmission dynamics of SARS-CoV-2, and today we've a new (preprint) study - authored by researchers at Demark's SSI (Statens Serum Institut) - that finds that while higher viral loads equate to greater transmissibility of SARS-CoV-2, even those with barely detectable virus (by RT-PCR) may be able to transmit the virus on to others.
This study also finds that older people are more likely to transmit the virus than younger people. Today's study raises new questions over the `cut-off' point for Ct values currently being used to infer infectivity.
First, a press release from Denmark's SSI on the findings, followed by a link and the abstract from the study.
Even very low levels of SARS-CoV-2 virus in humans infect others. And older people are more contagious
A new study from the Statens Serum Institut has looked at the connection between age, the amount of virus and infectivity of SARS-CoV-2.Last edited March 12, 2021
Researchers from the Statens Serum Institut (SSI) and the University of Copenhagen have, in a study, investigated the connection between age, viral load and infectivity of SARS-CoV-2, which is the virus that produces covid-19. The study looked at Danish households with 2-6 household members.
In the period from 25 August 2020 to 10 February 2021, a total of 66,602 people were identified who were the first in a household to test positive for SARS-CoV-2 with a PCR test in Testcenter Danmark (TCDK). In these households, 213,576 additional household members were registered, of which 103,389 (48%) were found positive in PCR tests 1-14 days after the first case in the household.
The Ct value
The Ct value is an expression of how many virus particles there are in a sample. The higher the Ct value, the fewer virus particles are present in the sample, and vice versa.
The results showed, as expected, that the lower the Ct value of the first infected person in a household (ie the more virus particles), the more household members became infected with SARS-CoV-2 (Figure 1).
Low virus incidence is contagious anyway
However, the results also showed that even at high Ct values (low viral load), infection with virus occurred. For example, a person with a Ct value of 38 had an 8% risk of infecting the other household members. A Ct value of 38 means that there was not much virus in the person's sample.
Impossible to set minimum limit for risk of infection
Based on laboratory studies, where Ct values are compared with the ability to grow viruses in cell cultures, several researchers have proposed a "cut-off" or a minimum limit of the Ct value of 30 for infectiousness. Thus, it was thought that people with a Ct value above 30 had such a small amount of virus in them that they did not pose any risk of infection.
However, the new study shows that it will not be possible to set a precise cut-off for infectivity. Even people with a very low amount of virus in their sample are able to infect household members with their virus. With a cut-off of 30 for infectivity, this study would not treat 42% of the original infected persons (27,937 people), and thus overlook 39% of the secondarily infected household members (40,776 people).
Older people are more contagious
The study also showed that no matter how much virus the first infected person in a household had, several other household members became infected with SARS-CoV-2 the older the first infected person was. The reason for this is not known.
This is one of the first studies to show the relationship between virus levels, measured by Ct values, age and risk of infection.
Read more
You can read more about the new studio here:
https://www.medrxiv.org/content/10.1101/2021.02.28.21252608v1
Association between SARS-CoV-2 Transmission Risk, Viral Load, and Age: A Nationwide Study in Danish Households
Frederik Plesner Lyngse, Kåre Mølbak, Kristina Træholt Frank, Claus Nielsen, Robert Leo Skov, Carsten Thure Kirkeby
doi: https://doi.org/10.1101/2021.02.28.21252608
This article is a preprint and has not been peer-reviewed [what does this mean?]
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Abstract
Aim The objective of this observational study was to investigate the association between SARS-CoV-2 transmission risk, RT-PCR Cycle threshold (Ct) values, and age of infected cases in Danish households.
Background The Covid-19 pandemic is one of the most serious global public health threats in recent times. Understanding transmission of SARS-CoV-2 is of utmost importance to be able to respond to outbreaks and take action against the spread of the disease. Viral load is generally thought to correlate with transmission risk.
Methods We used comprehensive administrative register data from Denmark, comprising the full population and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021), to estimate household transmission risk.
Results We found that the transmission risk was negatively associated—approximately linear—with the Ct values of the tested primary cases. Also, we found that even for relatively high Ct values, the risk of transmission was not negligible; e.g., for primary cases with a Ct value of 38, we found a transmission risk of 8%. This implies that there is no obvious cut-off for Ct values for risk of transmission. We estimated the transmission risk according to age and found an almost linearly increasing transmission risk with the age of the primary cases for adults (≥20 years) and negatively for children (<20 years). Age had a higher impact than Ct value on the risk of transmission.
Conclusions Lower Ct values (indicating higher viral load) are associated with higher risk of SARS-CoV-2 transmission. However, even at high Ct values, transmission occurs. In addition, we found a strong association between age and transmission risk, and this dominated the Ct value association.
