SARS-COV-2 PCR POSITIVITY AFTER VACCINATION
by Timothy Girgis (2614615G)
BIOL 2039 Fundamental Topics in Biology II
Dr. Stephanie Morand and Dr. Pam Scott
University of Glasgow Glasgow, Scotland
2/10/2021
It is not unreasonable for individuals to expect the worst when lacking an understanding of the science related to potential hazards, as with SARS-CoV-2 variants and vaccination. A recent BBC publication by Foster (2021) entitled, “Covid vaccines still effective against Delta variant,” based on a Polymerase Chain Reaction (PCR) study, should have alleviated public concern regarding variants and vaccination, but the article links another BBC publication that contradicts the message due to a misunderstanding of what PCR tests show. Thus, this essay will not only summarize the findings of the original article and the underlying study, but also discuss how PCR tests work and their limitations, before addressing the errors in the linked publication directly.
The BBC Article
Foster (2021) reports the primary findings of a study performed by Oxford University and the Nuffield Department of Medicine, which showed that AstraZeneca and Pfizer/BioNTech vaccines reduce “symptomatic” Delta variant infections by 71% and 93% respectively. The underlying study, which is the largest of its kind, relies entirely on PCR tests (Pouwels et al., 2021). PCR determines if a particular fragment of genetic material is present in a sample. Though there are several different methods, the gold standard for COVID-19 is RT-PCR, in which an enzyme known as reverse transcriptase is used to convert the RNA (as SARS-CoV-2 is an RNA-based virus) into complementary-DNA (cDNA).
Chemical reagents are then added along with fluorescent dye before the sample is run at various temperature cycles that help initiate the reactions necessary to replicate the newly formed cDNA. The degree of fluorescence is then measured to determine how much, if any, were reproduced. This process is illustrated in Figure 1 below.
Figure 1. COVID-19 Diagnostic Test: RT-qPCR Method and Process. (1) Swabs gather samples from the patient’s nasal passages; (2) samples are collected and may be stored up to 72 hours; (3) RNA is extracted; (4) extracted RNA is converted to cDNA via reverse transcriptase; PCR device measures fluorescence and reports the cycle threshold (Ct) - the number of cycles taken for detection of fluorescent signals, which is inversely related to viral load; Pouwels et al. (2021) use a Ct <30.00 for positivity (p. 6). Adapted from BioRender.com (2021).
Notably, this process only replicates the viral sequence if it is present, but unlike live cultures, the pathogen here does not need to be viable to be replicated. Thus, while PCR is effective at determining whether a person has been exposed to the virus relatively recently, it cannot determine infection. The standard for diagnosing infection is to identify symptoms in addition to obtaining a positive result, as ‘asymptomatic’ typically refers to a colonization or exposure (Louisiana Department of Health, 2017). To be infected in fact requires a viable infectious dose – meaning enough viral particles to overcome the innate white blood cell response and coax an antibody response (Khosroshahi and Mardomi, 2021). This issue lies at the heart of many misunderstandings regarding transmission, as with that of another BBC publication linked by Foster.
Gallagher’s Problematic Conclusion
Foster (2021) links readers to a BBC live news posting by Gallagher (2021), who concludes that vaccines appear to reduce disease severity, but not transmission. Evidently Gallagher, and the two authors he relied on – Public Health England and the U.S. CDC, failed to adequately contemplate that positive PCR results from asymptomatic individuals are likely not ‘infections,’ but exposures of quantities below the infectious dose Since shedding less than what was already not enough to infect is, by definition, certainly not enough to infect, it is not sound to conclude that vaccination does not reduce the risk of transmission. In short, given the research reported by Foster (2021), it is safe to assume that vaccination reduces the spread of COVID-19.
References
BioRender.com (2021) COVID-19 RT-PCR Diagram.. Available at: https://app.biorender.com/illustrations/6163e9edf40c7200ad26deb8
Foster, L. (2021) Covid vaccines still effective against Delta variant. BBC News. Available at: https://www.bbc.co.uk/news/health-58257863
Gallagher, J. (2021) Vaccines may not cut amount of Covid virus in the body, BBC Live
Reporting. Available at: https://www.bbc.co.uk/news/live/uk-58112093?
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Khosroshahi, H. and Mardomi, A. (2021). The initial infectious dose of SARS-CoV-2 and the severity of the disease: possible impact on the incubation period. Future Virology, 16(5), pp.369-373.
Louisiana Department of Health. (2017). Colonization vs Infection. Available at: https://ldh.la.gov/assets/oph/Center-PHCH/Center-CH/infectious-epi/HAI/ HAIworkshop2017/handoutsD1/ColonizationvInfection2017.pdf
Pouwels, K.B. et al. (2021). “Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK,” MedRxiv, pp. 1–39. doi:10.1101/2021.08.18.21262237