S-Variant SARS-CoV-2 Lineage B1.1.7 Is Associated With Significantly Higher Viral Load in Samples Tested by TaqPath Polymerase Chain Reaction
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Abstract
A SARS-CoV-2 variant B1.1.7 containing mutation Δ69/70 has spread rapidly in the United Kingdom and shows an identifiable profile in ThermoFisher TaqPath RT-qPCR, S gene target failure (SGTF). We analyzed recent test data for trends and significance. Linked cycle threshold (Ct) values for respiratory samples showed that a low Ct for ORF1ab and N were clearly associated with SGTF. Significantly more SGTF samples had higher inferred viral loads between 1×107 and 1×108. Our conclusion is that patients whose samples exhibit the SGTF profile are more likely to have high viral loads, which may explain higher infectivity and rapidity of spread.
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The Alpha variant was associated with threefold to eightfold higher upper-airway levels.
“It was also associated with threefold to eightfold higher upper-airway levels [199][200][201]”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [200]
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Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera
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“Finally, mRNA-1273 (18, 19) and BNT162b2 (18, 21) vaccine-induced sera showed ;3-8-fold reductions in crossneutralization of B.1.351.”
BackgroundInfluentialBayarri‐Olmos, R., Johnsen, L. B., Idorn, M., Reinert, L. S., Rosbjerg, A., Vang, S., Hansen, C. B., Helgstrand, C., Bjelke, J. R., Bak-Thomsen, T., et al. (2021) · eLife · doi:10.7554/elife.70002 · Cited by 33 · see citing works
Perchetti, G., Zhu, H.-Y., Mills, M., Shrestha, L., Wagner, C., Bakhash, S. M., Lin, M. J., Xie, H., Huang, M.-L., Mathias, P., et al. (2021) · medRxiv · doi:10.1002/jmv.27155 · Cited by 34 · see citing works
The Immune Response to SARS-CoV-2 and Variants of Concern
Torbati, E., Krause, K. L., & Ussher, J. E. (2021) · Viruses · doi:10.3390/v13101911 · Cited by 32 · see citing works
“The delta variant spike carries seven nucleotide changes and deletions compared to the spike of the ancestral Wuhan variant.”
BackgroundInfluentialOlsen, R. J., Christensen, P. A., Long, S. W., Subedi, S., Hodjat, P., Olson, R., Nguyen, M., Davis, J. J., Yerramilli, P., Saavedra, M. O., et al. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.07.002 · Cited by 30 · see citing works
Papageorgiou, V. Ε., & Tsaklidis, G. M. (2022) · Chaos Solitons & Fractals · doi:10.1016/j.chaos.2022.112914 · Cited by 31 · see citing works
“2 increased contagiousness [10], increased risk of hospitalization and ICU admission, as well as increased mortality [11–13].”
Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 InfectionsPreprint
Parker, M. D., Lindsey, B., Shah, D. R., Hsu, S., Keeley, A., Partridge, D., Leary, S., Cope, A., State, A., Johnson, K., et al. (2021) · bioRxiv · doi:10.1101/2021.03.02.433156 · Cited by 33 · see citing works
Evaluation of two RT-PCR screening assays for identifying SARS-CoV-2 variants
Migueres, M., Lhomme, S., Trémeaux, P., Dimeglio, C., Ranger, N., Latour, J., Dubois, M., Nicot, F., Miédougé, M., Mansuy, J., et al. (2021) · Journal of Clinical Virology · doi:10.1016/j.jcv.2021.104969 · Cited by 29 · see citing works
“7 lineage using the S gene dropout depends on the local epidemiology [6], being highly correlated when the circulation of this variant is predominant [7,16].”
BackgroundMethodClinical challenges of SARS‑CoV‑2 variants (Review)
Cojocaru, C., Cojocaru, E., Turcanu, A., & Zaharia, D. C. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11343 · Cited by 29 · see citing works
High throughput diagnostics and dynamic risk assessment of SARS-CoV-2 variants of concern
Gravagnuolo, A. M., Faqih, L., Cronshaw, C., Wynn, J., Burglin, L., Klapper, P. E., & Wigglesworth, M. J. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103540 · Cited by 30 · see citing works
“non-vaccinated cohorts [26,35], making possible a comprehensive risk assessment for the population [19], thus, informing decision makers to undertake balanced and controlled measures [36,37].”
de Souza, A. S., Amorim, V. M. D. F., Guardia, G. D. A., dos Santos, F. F., Ulrich, H., Galante, P. A. F., de Souza, R. F., & Guzzo, C. R. (2022) · Viruses · doi:10.3390/v14040827 · Cited by 28 · see citing works
“4 [70,83], driven by higher viral loads (PCR Ct values) [68,84], shorter time to peak viral load (shorter incubation period [70,83]), longer viral shedding (slower decline) and abrogated neutralization capacity compared to non-Delta SARS-CoV-2 variants [43] (Table 2).”
BackgroundSurveillance of SARS-CoV-2 lineage B.1.1.7 in Slovakia using a novel, multiplexed RT-qPCR assay
Boršová, K., Paul, E. D., Kováčová, V., Radvánszka, M., Hajdu, R., Čabanová, V., Slavíková, M., Ličková, M., Lukáčiková, Ľ., Belák, A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-99661-7 · Cited by 27 · see citing works
Ratcliff, J., Nguyen, D. V., Fish, M., Rynne, J., Jennings, A., Williams, S. V., Al-Beidh, F., Bonsall, D., Evans, A. L., Golubchik, T., et al. (2021) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiab283 · Cited by 25 · see citing works
Diagnosing SARS-CoV-2 with Antigen Testing, Transcription-Mediated Amplification and Real-Time PCR
Dierks, S., Bader, O., Schwanbeck, J., Groß, U., Weig, M., Mese, K., Lugert, R., Bohne, W., Hahn, A., Feltgen, N., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112404 · Cited by 26 · see citing works
Lee, B. U. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18189804 · Cited by 26 · see citing works
Radu, E. L., Masseron, A., Amman, F., Schedl, A., Agerer, B., Endler, L., Penz, T., Bock, C., Bergthaler, A., Vierheilig, J., et al. (2022) · Water Research · doi:10.1016/j.watres.2022.118257 · Cited by 25 · see citing works
“Recent studies underline our statement that SARS-CoV-2 alpha variant presents a higher viral load in the respiratory tract as well as in stool (Frampton et al., 2021; Kidd et al., 2021; Rosenke et al., 2021).”
Fang, L., Xu, J., Zhao, Y., Fan, J., Shen, J., Liu, W., & Cao, G. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1228128 · Cited by 26 · see citing works
Teyssou, E., Soulié, C., Visseaux, B., Lambert-Niclot, S., Ferré, V. M., Marot, S., Jary, A., Sayon, S., Zafilaza, K., Leducq, V., et al. (2021) · Journal of Infection · doi:10.1016/j.jinf.2021.04.023 · Cited by 24 · see citing works
Vimalanathan, S., Shehata, M., Kannan, S., Delbue, S., Dolci, M., Pariani, E., D’Alessandro, S., & Pleschka, S. (2022) · Microorganisms · doi:10.3390/microorganisms10112145 · Cited by 24 · see citing works
Lythgoe, K., Golubchik, T., Hall, M. D., House, T., Cahuantzi, R., MacIntyre-Cockett, G., Fryer, H. R., Thomson, L., Nurtay, A., Ghafari, M., et al. (2023) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2023.1284 · Cited by 28 · see citing works
Shastri, J. S., Parikh, S., Agrawal, S. R., Chatterjee, N., Pathak, M., Chaudhary, S., Sharma, C., Kanakan, A., Vivekanand, A., Vasudevan, J. S., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.631769 · Cited by 23 · see citing works
Kim, H. N., Yoon, S., Lim, C. S., & Yoon, J. H. (2022) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.24242 · Cited by 23 · see citing works
An overview of the ongoing challenges in SARS-CoV-2 global control
Shehata, A. A., Parvin, R., Nagy, A., Wang, Y., Azhar, T. M., Attia, Y. A., Azhar, E. I., Paul, A. K., & Rahmatullah, M. (2021) · German Journal of Microbiology · doi:10.51585/gjm.2021.2.0006 · Cited by 24 · see citing works
Monel, B., Planas, D., Grzelak, L., Smith, N., Robillard, N., Staropoli, I., Gonçalves, P., Porrot, F., Guivel‐Benhassine, F., Guinet, N. D., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103637 · Cited by 21 · see citing works
“It has alternatively been observed that alpha is associated with higher viral RNA loads than non-alpha viruses [10,11].”
Kohmer, N., Eckermann, L., Böddinghaus, B., Götsch, U., Berger, A., Herrmann, E. M., Kortenbusch, M., Tinnemann, P., Gottschalk, R., Hoehl, S., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10245751 · Cited by 22 · see citing works
“Higher diagnostic sensitivity is likely attributable to higher virus concentrations observed in patients infected with the Alpha variant, also observed elsewhere [28,29].”
BackgroundSARS-CoV-2 infection and immune responses
Harne, R., Williams, B., Abdelaal, H. F. M., Baldwin, S. L., & Coler, R. N. (2023) · AIMS Microbiology · doi:10.3934/microbiol.2023015 · Cited by 21 · see citing works
Fast detection of SARS-CoV-2 variants including Omicron using one-step RT-PCR and Sanger sequencing
Bloemen, M., Rector, A., Swinnen, J., Ranst, M. A. V., Maes, P., Vanmechelen, B., & Wollants, E. (2022) · Journal of Virological Methods · doi:10.1016/j.jviromet.2022.114512 · Cited by 20 · see citing works
Chen, Y., Mason, G. H., Scourfield, D. O., Greenshields‐Watson, A., Haigh, T. A., Sewell, A. K., Long, H. M., Gallimore, A., Rizkallah, P. J., MacLachlan, B. J., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112827 · Cited by 22 · see citing works
Loconsole, D., Sallustio, A., Accogli, M., Leaci, A., Sanguedolce, A., Parisi, A., & Chironna, M. (2021) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2021.05.007 · Cited by 20 · see citing works
“It is hypothesized that SARS-CoV-2 variants are capable of at least partially evading vaccine-induced immunity, and that they replicate more efficiently [8]; in fact, all vaccinated cases described herein had a high viral load (Ct < 21).”
Parker, M. D., Stewart, H., Shehata, O. M., Lindsey, B. B., Shah, D. R., Hsu, S. N., Keeley, A. J., Partridge, D. G., Leary, S., Cope, A., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03565-9 · Cited by 49 · see citing works
Estimating Vaccine Efficacy Against Transmission via Effect on Viral Load
Kennedy‐Shaffer, L., Kahn, R. J., & Lipsitch, M. (2021) · Epidemiology · doi:10.1097/ede.0000000000001415 · Cited by 19 · see citing works
Lessons from SARS-CoV, MERS-CoV, and SARS-CoV-2 Infections: What We Know So Far
Alsafi, R. (2022) · Canadian Journal of Infectious Diseases and Medical Microbiology · doi:10.1155/2022/1156273 · Cited by 20 · see citing works
Intra-Host Evolution Provides for the Continuous Emergence of SARS-CoV-2 Variants
Landis, J. T., Moorad, R., Pluta, L., Caro‐Vegas, C., McNamara, R. P., Eason, A. B., Bailey, A., Villamor, F. C. S., Juarez, A., Wong, J. P., et al. (2023) · mBio · doi:10.1128/mbio.03448-22 · Cited by 19 · see citing works
SARS-CoV-2 variants: Subversion of antibody response and predicted impact on T cell recognition
Altmann, D. M., Reynolds, C. J., & Boyton, R. J. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100286 · Cited by 19 · see citing works
“Implicated mechanisms rest largely on the notion of improved binding to ACE2 and increased viral load in nasopharyngeal samples.(5) There has been concern and speculation about the possibility that some of these mutations may facilitate immune evasion, with implications both for risk of reinfection in those previously…”
BackgroundWang, B., Goh, Y. S., Prince, T., Ngoh, E. Z. X., Salleh, S. N. M., Hor, P. X., Loh, C. Y., Fong, S., Hartley, C. S., Tan, S. Y., et al. (2021) · npj Vaccines · doi:10.1038/s41541-021-00389-2 · Cited by 19 · see citing works
Alpha variant SARS-CoV-2 infection: How it all starts
Domingo, P., & Benito, N. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103703 · Cited by 18 · see citing works
“Mechanistic explanations for its enhanced transmissibility included higher nasopharyngeal viral load and prolonged viral shedding [4,5].”
BackgroundKovačech, B., Fialova, L., Filipcik, P., Škrabana, R., Zilkova, M., Paulenka-Ivanovova, N., Kováč, A., Palova, D., Rolkova, G., Tomková, K., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103818 · Cited by 16 · see citing works
One assay to test them all: Multiplex assays for expansion of respiratory virus surveillance
Boukli, N., Flamand, C., Chea, K. L., Heng, L., Keo, S., Sour, K., In, S., Chhim, P., Chhor, B., Kruy, L., et al. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1161268 · Cited by 18 · see citing works
Papageorgiou, V. Ε., & Tsaklidis, G. M. (2024) · Mathematical Methods in the Applied Sciences · doi:10.1002/mma.9934 · Cited by 18 · see citing works
“On the other hand, the emergence of variants has been associated with increased transmissibility [13], hospitalizations, and mortality [14 – 16].”
Background
- Authors
- Kidd, M., Richter, A., Best, A., Cumley, N., Mirza, J., Percival, B., Mayhew, M., Megram, O., Ashford, F., White, T., Moles-Garcia, E., Crawford, L., Bosworth, A., Atabani, S. F., Plant, T., & McNally, A.
- Affiliations
- University Hospitals Birmingham NHS Foundation Trust (GB)
- University of Birmingham (GB)
- Corresponding author
- Kidd, Michael
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-02-13
- Volume
- 223
- Issue
- 10
- Pages
- 1666-1670
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC7928763
- OpenAlex
- W3128016658
- Cited by
- 237
- References
- 3
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 12 · 2023: 31 · 2022: 67 · 2021: 116
- FWCI
- 17.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- UK Department of Health and Social Care
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, B.1.1.7 variant, S-gene target failure, viral load, cycle threshold, ORF1ab, N gene, infectivity, COVID-19 diagnosis
- MeSH terms
- COVID-19, SARS-CoV-2, Humans, Linear Models, Polymerase Chain Reaction, Viral Load, Taq Polymerase
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