RE:Interesting This is a lengthy scientific type dissertation so I tried to pull out some of the more pertinent excerpts -- from my point of view:
Abstract
“The COVID-19 pandemic has created a public health crisis.
Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust population screening, for which virus testing will often be central.
After infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential viral growth, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance. Given the pattern of viral load kinetics, we model the effectiveness of repeated population screening considering test sensitivities, frequency, and sample-to-answer reporting time.
These results demonstrate that effective screening depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity.
We therefore conclude that screening should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.”
The reliance on testing as a means to safely reopen societies has placed a microscope on the analytical sensitivity of virus assays, with a gold-standard of quantitative real-time polymerase chain reaction (qPCR). However, qPCR remains expensive and as a laboratory-based assay often have sample-to-result times of 24-48 hours.
New developments in SARS-CoV-2 diagnostics i.e. Rapid Antigen Tests, have the potential to reduce cost significantly, allowing for expanded testing or greater frequency of testing and can reduce turnaround time to minutes. These assays however largely do not meet the gold standard for analytical sensitivity, which has encumbered the widespread use of these assays.
We observed that a population screening regimen administering either test with high frequency limited viral spread, measured by both a reduction in the reproductive number R (Figs. 2A and B; see Methods for calculation procedure) and by the total infections that persisted in spite of different screening programs, expressed relative to no screening (Figs. 2C and D).
Testing frequency was found to be the primary driver of population-level epidemic control, with only a small margin of improvement provided by using a more sensitive test. Direct examination of simulations showed that with no testing or biweekly testing, infections were uncontrolled, whereas screening weekly with either LOD = 103 or 105 effectively attenuated surges of infections (examples shown in Fig. 3).
We simulated epidemics in which screening began only at the point when uncontrolled infections reached 4% prevalence. Based on results from our previous analyses, we considered a less sensitive but rapid test with LOD 105 cp/ml and a zero-day delay in results, and further assumed that 10% of would-be positive samples would be negative due to improper sample collection.
We then examined scenarios of testing every 3 days and every 7 days, with either 50% or 75% of individuals participating, starting from a partially mitigated R0 = 1.5. We found that testing 75% of individuals every 3 days was sufficient to drive the epidemic toward extinction within 6 weeks and reduce cumulative incidence by 88%, and that other combinations also had successful but less rapid mitigating impacts, particularly when compared with no intervention.
Notably, even weekly testing with 50% participation was able to reduce the peak and length of the outbreak, illustrating how even partial screening using a test with 100X lower molecular sensitivity than PCR can have public health benefits when used frequently. Repeating these simulations using a test with LOD 106 led to similar results. To further generalize these results, we modified our mathematical formula to predict the impacts of per-individual test refusal and per-test sampling-related sensitivity on the reproductive number R.
Our results lead us to conclude that repeated population screening of asymptomatic individuals can be used to limit the spread of SARS-CoV-2. However, our findings are subject to a number of limitations.
A critical point is that the requirements for screening tests are distinct from clinical tests. Clinical diagnoses target symptomatic individuals, need high accuracy and sensitivity, and are not limited by cost. Because they focus on symptomatic individuals, those individuals can isolate such that a diagnosis delay does not lead to additional infections. In contrast, results from the screening of asymptomatic individuals need to be returned quickly, since even a single day diagnosis delay compromises the screening program’s effectiveness. Indeed, at least for viruses with infection kinetics similar to SARS-CoV-2, we find that speed of reporting is much more important than sensitivity, although more sensitive tests are nevertheless somewhat more effective.
The difference between clinical and screening tests highlights the need for additional tests to be approved and utilized for screening. Such tests should not be held to the same degree of sensitivity as clinical tests, in particular if doing so encumbers rapid deployment of faster cheaper SARS-CoV-2 assays. We suggest that the FDA, other agencies, or state governments, encourage the development and use of alternative faster and lower cost tests for public health and repeated population screening purposes, even if they have poorer limits of detection. If the availability of point-of-care or self-administered screening tests leads to faster turnaround time or more frequent testing, our results suggest that they would have high epidemiological value.
Our modeling suggests that some types of repeated population screening will subject some individuals to unnecessary quarantine days. For instance, the infrequent use of a sensitive test will not only identify (i) those with a low viral load in the beginning of the infection, who must be isolated to limit viral spread, but (ii) those in the recovery period, who still have detectable virus or RNA but are below the infectious threshold. Isolating this second group of patients will have no impact on viral spread but will incur costs of isolation, as would the isolation of individuals who received a false positive test result due to imperfect test specificity. The use of serology, repeat testing 24 or 48 hours apart, or some other test, to distinguish low viral load patients on the upslope of infection from those in the recovery phase could allow for more effective quarantine decisions.