Cambridge CLDC Testing
Characteristic Leucocyte
Different Count
Excerpt from a paper “Model for rapid reduction of R (reproduction number) to below 1” written by Dr. Mark Baker
■Abstract and Background
We present an open-source model that allows quantitative prediction of the effects on the degree of quarantine, isolation, and lockdown required to limit COVID-19 by comparing CLDC testing with other testing methods.
SARS-CoV-2 (COVID-19) is most infectious 24-48 hours before symptoms occur and at symptom onset.
Therefore, many countries are attempting to control the effective reproduction number (R) which indicates the number of people infected on average by each one infected person as one of further challenges.
■Effectiveness of measures
The aim of measures put in place is to reduce R by reducing the number of people with whom infectious people come into contact, including those who are infectious but do not yet know it.
The tests currently in use (lateral flow and PCR) are of limited value particularly as they have little ability to detect the virus prior to the onset of symptoms, which is part of the most infectious period.
■Objective
The aim is to allow improved mitigation of Omicron, and control of future highly transmissible variants of concern.
Importantly, the widely used PCR and lateral flow tests, where real world sensitivity is relatively low, resulted in significant proportions of infectious individuals (false negatives) circulating. This means the disease is not controlled by these test types.
■ Protocol
A testing population size of 100,000 is used with 30% of those tested being infectious
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Of all individuals tested on day 1, those who receive a positive result are told to isolate, and those who receive a negative result may circulate.
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All those who received a positive result on day 1 are retested on day 2. Those who received a negative result on day 1 are not retested and continue circulating.
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Of those retested on day 2, those who receive a positive result again are told to continue isolating, and those who now receive a negative result may now circulate.
■ CLDC testing
CLDC testing, where specificity is relatively low but sensitivity is high, minimizes the number of infectious individuals (false negatives) circulating and has an R reduction multiplier around 10 times smaller with one or two days of testing
CLDC
Lateral Flow Antigen Test
PCR (soon after symptom onset)
PCR (two days before symptom onset)
■ Outcomes
Below figures show the outcomes when the number of days for the testing is 2.
Of particular interest are, regardless of the R value level, the number of susceptible individuals isolating for the recommended period as a result of false positive test results (which has social, economic and other health impacts), and the number of infectious individuals circulating as a result of false negative test results (which needs to be minimized to reduce transmission).
■ Sensitivity and Specificity
Sensitivity: the ability of a test to correctly identify patients who DO have the disease.
Specificity: the ability of a test to correctly identify people who do NOT have the disease.
■ If a test’s sensitivity is 70%
For every 100 infectious people tested, 70 infectious people are given a correct positive result (true positives) and 30 infectious people are given incorrect negative results (false negatives).
This means 30% of the infectious people are circulating in the population, allowing spread of the disease at 30% of the unrestricted rate.
■ If a test’s specificity is 70%
For every 100 uninfected people tested, 70 of them are given correct negative results (true negatives) and 30 of them are given incorrect positive results (false positives).
70% of the uninfected people will be able to carry on as normal, while 30% of them have to isolate.
In the absence of 100% sensitive 100 % specific testing there is a trade-off between those with false positive results isolating unnecessarily and those with false negative results circulating and spreading infection.
Use of this model in conjunction with CLDC testing has the potential to reduce R, reduce the number of individuals needing to isolate, and make it possible to apply measures earlier and in a more nuanced way to substantially reduce the impact of future waves and mitigate the adverse health, social and economic impacts of COVID-19.