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 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 sensitivity is unknown. Methods: We combined SARS-CoV-2 testing and contact tracing data from England between 01-September-2020 and 28-February-2021. We used multivariable logistic regression to investigate relationships between 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 one of four LFDs. Results: 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 Ct values) e.g., 11.7%(95%CI 11.5-12.0%) at Ct=15 and 4.5%(4.4-4.6%) at Ct=30. B.1.1.7 infection increased PCR-positive results by ~50%, (e.g. 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%[6.8-7.3%]), contacts at events/activities (5.2%[4.9-5.4%]), work/education (4.6%[4.4-4.8%]), and least common after outdoor contact (2.9%[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%(89.4-89.6%) and 83.0%(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.

Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study

“…We considered Ct values, which correlate with the ability to isolate virus, 39 to be indicative of infectivity. 40 Although it is challenging to compare Ct values across different assays, all results targeted the same genes (N, ORF1ab, S), and similar findings were obtained in a sensitivity analysis based on a single assay. Our analysis was restricted by absence of data on underlying conditions and frailty status of individual residents, and by scarcity of reliable symptom data, which precluded analysis of vaccine effectiveness against symptomatic infections, as well as reporting on vaccine safety.…”

Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time

“…With recent expansion of antigen assays, there has been considerable debate on what “positivity” means, and hence what is a “false-positive” or a “false-negative”. First, it is clear that the detection of viral RNA is neither the same as infectiousness, although a strong relationship between Ct values and infection in contacts is observed (L. Y. W. Lee et al, 2021), nor a “disease” in its own right. However, surveillance has very distinct goals from clinical testing with its focus on isolation and contact tracing, particularly given the large percentage of asymptomatic infections.…”

Interpreting a lateral flow SARS-CoV-2 antigen test

“…23 Evidence shows a strong correlation between Ct values and in vitro infectiousness 24 and some evidence for increased risk of transmission from patients with lower Ct values. 25 However, no agreed Ct threshold exists for infectiousness. Transmission is also likely to be influenced by other factors (eg, host immunity, social distancing, and mask wearing) as well as how infectious the case is.…”