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

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.

Keywords: B.1.1.7 variant; SARS-CoV-2; contact tracing; infectivity; lateral flow device.

Figure 1.

Index cases and contacts in England, 1 September 2020 to 28 February 2021. Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction.

Figure 2.

Relationship between PCR Ct value in cases and the proportion of their contacts with a PCR positive result, by contact type and S gene target failure. Model predictions are plotted after adjustment for index case age (set to the median value, 35 years), case ethnicity (set to White), index of multiple deprivation score at contact’s home address (set to median, 14 465), incidence at contact’s home address (set to median 350 cases per 100 000 population per week) and index case sex (set to female). Shaded area indicates the 95% confidence interval. Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction.

Figure 3.

Relationship between PCR-positive results in contacts and index case Ct value and SGTF indicative of the B.1.1.7 variant. A, Proportion of contacts testing by PCR-positive. B, Ratio of the 2 lines from panel A, ie, the relative infectiousness of index cases with SGTF vs without SGTF. Model predictions are adjusted for index case age, sex and ethnicity, contact index of multiple deprivation and incidence as in Figure 2. Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction; SGTF, S gene target failure.

Figure 4.

Relationship between index case age and the proportion of their contacts with a PCR positive result, by contact type and S gene target failure. Model predictions are plotted after adjustment for Ct value (set to the median Ct value, 20.1), and other variables as in Figure 2. Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction.

Figure 5.

Simulated proportion of cases with a PCR-positive contact detected using 4 LFDs. Proportion of cases detected by estimated PCR viral load (PCR cycle threshold, Ct value) is shown in the PCR column. Number of cases with a PCR-positive contact who would be detected using each LFD is shown for 4 LFDs. Abbreviations: Ct, cycle threshold; LFD, lateral flow devices; PCR, polymerase chain reaction.