Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectivity by Viral Load, S Gene Variants and Demographic Factors, and the Utility of Lateral Flow Devices to Prevent Transmission

Lennard Y.W. Lee, Stefan Rozmanowski, Matthew Pang, Andre Charlett, Charlotte Anderson, Gareth J. Hughes, Matthew Barnard, Leon Peto, Richard Vipond, Alex Sienkiewicz, Susan Hopkins, John Bell, Derrick W. Crook, Nick Gent, A. Sarah Walker, Tim E.A. Peto, David W. Eyre*

*Corresponding author for this work

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Abstract

Background: How severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect clinical sensitivity is unknown. 

Methods: We combined SARS-CoV-2 testing and contact tracing data from England between 1 September 2020 and 28 February 2021. We used multivariable logistic regression to investigate relationships between polymerase chain reaction (PCR)-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using 1 of 4 LFDs. 

Results: In total, 231 498/2 474 066 (9%) contacts of 1 064 004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower cycle threshold [Ct] values), for example, 11.7% (95% confidence interval [CI] 11.5-12.0%) at Ct = 15 and 4.5% (95% CI 4.4-4.6%) at Ct = 30. B.1.1.7 infection increased PCR-positive results by ∼50%, (eg, 1.55-fold, 95% CI 1.49-1.61, at Ct = 20). PCR-positive results were most common in household contacts (at Ct = 20.1, 8.7% [95% CI 8.6-8.9%]), followed by household visitors (7.1% [95% CI 6.8-7.3%]), contacts at events/activities (5.2% [95% CI 4.9-5.4%]), work/education (4.6% [95% CI 4.4-4.8%]), and least common after outdoor contact (2.9% [95% CI 2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5% (95% CI 89.4-89.6%) and 83.0% (95% CI 82.8-83.1%) of cases with PCR-positive contacts, respectively. 

Conclusions: SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ∼50%. The best performing LFDs detect most infectious cases.

Original languageEnglish
Pages (from-to)407-415
Number of pages9
JournalClinical Infectious Diseases
Volume74
Issue number3
Early online date11 May 2021
DOIs
Publication statusPublished - 1 Feb 2022

Bibliographical note

Funding Information: This work was supported by the UK Government’s Department of Health and Social Care. This work was supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England (PHE) (NIHR200915), and the NIHR Biomedical Research Centre, Oxford. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health or Public Health England. L. Y. W. L. is supported by the NIHR Oxford BRC. A. S. W. is an NIHR Senior Investigator. D. W. E. is a Robertson Foundation Fellow and an NIHR Oxford BRC Senior Fellow.
L. Y. W. L. reports speaker fees from the Merck group and Servier, outside the submitted work. D. W. E. reports lecture fees from Gilead, outside the submitted work. M. P. and S. R. report employment from Accenture. S. R. reports that DHSC were supplied professional services by Accenture. All other authors report no potential conflicts.

Open Access: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Citation: Lennard Y W Lee, Stefan Rozmanowski, Matthew Pang, Andre Charlett, Charlotte Anderson, Gareth J Hughes, Matthew Barnard, Leon Peto, Richard Vipond, Alex Sienkiewicz, Susan Hopkins, John Bell, Derrick W Crook, Nick Gent, A Sarah Walker, Tim E A Peto, David W Eyre, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectivity by Viral Load, S Gene Variants and Demographic Factors, and the Utility of Lateral Flow Devices to Prevent Transmission, Clinical Infectious Diseases, Volume 74, Issue 3, 1 February 2022, Pages 407–415, https://doi.org/10.1093/cid/ciab421

DOI: https://doi.org/10.1093/cid/ciab421

Keywords

  • B.1.1.7 variant
  • SARS-CoV-2
  • contact tracing
  • infectivity
  • lateral flow device

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