Only 25% of SARS-CoV-2 infections have been detected in the UK: Study

Diagnostic test, Contact tracing, And the isolation of infected individuals and their contacts form the basis for managing the current Coronavirus Disease 2019 (COVID-19) pandemic. In addition, the number of positive tests is an important measure of the severity of outbreaks at the regional, national, and international levels.

The true number of infections with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is also essential for calculating the actual incidence and mortality of the disease. In addition, it helps to understand how effective control measures are in controlling the spread of the virus.

However, many infected individuals have not been tested and many others have been falsely declared negative due to the insensitivity of the test. Therefore, the total number of cases is unknown.New preprint research treatise submitted to medRxiv* The server estimates that the number of infections diagnosed by testing alone is about a quarter of the total.

Two data sources

Examining a symptomatic individual with a fairly sensitive test usually underestimates the total number of infections, but is essential to identify hotspots of infection.

Random tests, on the other hand, provide a more accurate estimate of the overall prevalence of infection, but are not applicable to infected clusters. Both types of data were available to researchers to answer questions about the percentage of total infections identified by the test.

Researchers used many UK data sources to reach estimates and combined positive test results with a range of incubation periods and changes in test sensitivity over time. The source was the daily publication of the number of positive tests between individuals suspected of being infected by the British Government. Publication of population prevalence by the National Bureau of Statistics (ONS).

The former is based on several diagnostic tests. The first is the polymerase chain reaction (PCR) test, the sensitivity of which depends on the stage of infection. The other is the use of rapid point-of-care tests using lateral flow devices (LFDs) in schools, home care centers, and other environments at high risk of infection for potential contact and infected individuals. Used to screen for. These are relatively less sensitive than PCR, but give faster results, especially if not performed by a specialist.

ONS data is based on random sampling and is more accurate. Researchers adjusted the number of diagnostic tests on ONS data to reach estimates.

Impact of VOCs

Newly emerging variants of the SARS-CoV-2 virus pose challenges in terms of a variety of clinical manifestations.This can be accompanied by different incubation periods and different speeds Viral shedding, And another pathology.

These new variants can also make a difference in test results and the number of people seeking tests. Of course, this affects the rate of infection reported by diagnostic tests.

Number of people with a positive SARS-CoV-2 test in each of the United Kingdom (top) and nine regions of the United Kingdom (bottom). The blue circles show the estimates given in Eq. (6), and the black triangles show the ONS infection survey data.

Differences in reporting rates by region

Differences in the proportion of reported cases by region and over time may be a new way to understand how these mutations are present. In the southern part of England, there is a significant difference in case reports compared to other parts in that the rate of reported infections increased until early December 2020. In other regions, the percentage has declined. This is despite the fact that testing has grown steadily in all regions and is currently only being performed by PCR.

Reported increase in infection

The increase in infections reported in all regions between November and December 2020 is due, at least in part, to the increased proportion of infections caused by UK Concern Variants (VOCs) during this period. It may be. The reported infection rate may be higher due to some evidence that the mutant is more toxic compared to the parent strain.

Another reason is the adoption of lateral flow device (LFD) tests for extensive screening, which may increase the number of asymptomatic infections reported. Therefore, the researchers excluded an estimated number of positive LFD tests from the total to obtain an estimate of the rate of infection reported by positive PCR.

Higher LFD positive rates reduce the rate of infections reported by VOCs.

VOC reporting rate is high

Nonetheless, VOCs have a higher proportion of reported cases than older variants, indicating that this is the main reason for the increase in cases reported since November. This assumes that the positive ratio of LFD remains constant over time.

Overall, they found that 25% of non-VOC variants vary by region and are reported throughout England. With a zero LFD positive rate, 32% of VOC infections were reported.

VOC detection period may be longer

They also investigated the possibility that detection of VOC-induced infections could occur for a longer period of time, that is, for more than 3 weeks after exposure. In such cases, infections detected 3 weeks after exposure (historical infections) are more likely to be part of the ONS estimate than daily positive test reports.

If the PCR cycle threshold is high, it is likely that a past infection was detected. In such cases, the test used for the ONS sampling survey requires an average cycle threshold that corresponds to the rate of past infections.

In fact, researchers found that the highest threshold of the ONS cycle correlates with the period during which prevalence estimates were below ONS numbers. In some regions, reporting rates are inversely correlated with cycle thresholds reported by ONS, supporting the hypothesis that test sensitivity also contributes to changes in reported VOC infections.

What is the impact?

The report shows that there is a significant variation in the percentage of positive tests in the UK. Researchers attribute this to the difference in test seeks between the north and south of England. Towards the end of the year, the number of tests required in the northern region has declined significantly, leading to the spread of uncontrolled viruses.

This observation should be confirmed as it is important in determining how the infection can spread and which control measures are most beneficial.

About 25% of older variants have been reported, but VOC reporting rates appear to be as high as 32%. Considering this change, VOC reporting rates may be higher. However, other factors may also be working.

Sudden changes may be clues to other previously unrecognized changes. If so, the current state of knowledge about SARS-CoV-2 may soon become apparent as obsolete.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.