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, André Charlett, Charlotte Anderson, G. Hughes, Matthew Barnard, Leon Peto, Richard Vipond, Alex Sienkiewicz, Susan Hopkins, John I. Bell, Derrick W. Crook, Nick Gent, A. Sarah Walker, Tim Peto, David W. Eyre
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.