How accurate are COVID tests?

Symptom-based screenings using SARS-CoV-2 tests, by design, fail to identify all COVID-19 infections. Multiple studies have confirmed that individuals that are asymptomatic (never developed symptoms - about 23% of infected people (11)) and presymptomatic (developed symptoms later on - about 44% of infected people (12)) can contribute to SARS-CoV-2 transmission.
Understanding how, when and in which settings infected people transmit the virus is important for developing and implementing control measures to break chains of transmission. In this blog post, we focus on the risk that non-symptomatic people pose for transmission of the virus, and how coronavirus surface testing can mitigate this risk.

 

When do people infected with COVID-19 infect others?

Back in June, the WHO published a scientific brief outlining what is known about when a person may be able to spread the COVID-19 virus SARS-CoV-2 (1). It is well known that infected persons who have symptoms can infect others primarily through droplets and close contact and state recommendations for COVID protection focus on detecting symptoms through temperature check for example. However multiple studies have now shown that people can also infect others even when they are not ill themselves (1-2; 13-17). In particular, one study of transmission in Singapore reported that 6.4% of secondary cases resulted from pre-symptomatic transmission (18). This data, together with the reality that entire groups cannot reasonably undergo COVID testing daily or even weekly for an extended period of time, highlights the need for an alternative SARS-CoV-2 test to detect the virus within groups who are expected to spend time together in closed environments. Despite social distancing, PPE guidelines and the willingness to follow them, the re-opening or continued functioning of facilities increases the risk of transmission of a virus as highly contagious as SARS-CoV-2.

 

“97.5% of people infected with SARS-CoV-2 will exhibit symptoms by 11.5 days.” 

 Stephen A. Lauer, MS, PhD, Researcher in the Infectious Disease Dynamics Group at Johns Hopkins Bloomberg School of Public Health (26)

 

As long-term care professionals know too well, the highest risk of infection in those communities comes from staff members, who have to navigate in and out of the facilities, often between high-risk communities. Despite extensive precautions instaurated and diligently followed, keeping community members safe remains a difficult task when 40-50% of infected people are asymptomatic or presymptomatic (5, 6, 11, 12).

 

"Following identification of a case of COVID-19 in a healthcare worker, 30% of residents of a Skilled Nursing Facility (SNF) had positive test results, approximately half of whom were asymptomatic or presymptomatic on the day of testing."(6)

 

Human testing for COVID-19 is invasive, sometimes painful, expensive and even inaccessible for some. Most people will not get tested unless they show symptoms. In addition, the surge of COVID cases around the US have extended the delay to receiving test results to weeks, when what is needed to control the spread of the disease is a turnaround time measurable in hours if not minutes. Another hurdle to regular COVID-19 testing in groups of people is that it can be cost prohibitive and mentally taxing.

So how can facility managers reasonably ensure the safety of their community members? Are there any COVID testing solutions that could offset the need for large human testing campaigns to identify the presence of asymptomatic spreaders within a community?

 

How reliable are COVID tests?

Concerns over the reliability of COVID test kits are growing. It is also worth noting that detecting the presence of the virus does not necessarily mean that a person is infectious and able to transmit the virus to another person. However, coronavirus testing provides awareness of an infection and the opportunity to take the necessary precautions to stop the spread of the virus.

 

What COVID tests look for

The availability of the complete genome of COVID-19 early in the pandemic facilitated the development of tests that detect viral genetic material (RNA) (19). In fact, multiple assays with different SARS-CoV-2 gene targets have been developed since then. Those SARS-CoV-2 tests use a routine lab technique called reverse transcriptase polymerase chain reaction or PCR (20). Samples are put in the presence of molecules that target and multiply parts of RNA that are specific to the virus. In the case of COVID human testing, those samples are usually obtained directly from the respiratory tract of a patient who is exhibiting symptoms commonly associated with COVID-19  (nasopharyngeal swab). Companies like Enviral Tech have modified PCR tests to detect the presence of SARS-CoV-2 on surfaces, creating a proxy for the detection of infected individuals in a building.

 

Why no test is perfect

Ideally, a viral test would both detect those who have been infected and tell when the virus was never present, with 100% accuracy. However nothing is ever 100% accurate when it comes to biology. What's more, tests are used to discover whether the patient or surface being tested was exposed to the virus, so it is hard to know when a result is a true positive or a true negative. So instead scientists use samples they know are negative or positive for SARS-CoV-2 as a way to check the reliability of the test results. That means testing a sample with random shards of genetic material or one spiked with viral molecules. This tells researchers how often a test produces false positive and false negative results. In general, a good test correctly identifies known positives and negatives at least 95% of the time. PCR testing is a highly specific technique, despite its moderate sensitivity. This means that when a test is positive, it is very likely that the genetic material amplified was indeed from SARS-CoV-2, meaning that the virus was indeed present in the original sample.

 

False positive and false negatives: definitions (25)

  • Specificity or the true positive rate is the probability that a test will result positive (find the presence of the virus) when the virus is indeed present. 100% specificity means that when a test is positive, it is always a true positive. The test cannot mistakenly detect anything other than SARS-CoV-2.
  • The accuracy of a test is its ability to differentiate the infected and healthy subjects correctly. A 100% accurate test means that it is never wrong regardless of the result. To get a test’s accuracy rate, you need to know for sure that the subject/sample was positive or negative for COVID-19 virus, which is challenging.
  • Sensitivity represents the probability that a test will detect all infected samples. A test that is 100% sensitive will identify every single infected subject tested.
  • False Negative: infected subjects were incorrectly identified as not infected
  • True Positive: infected subjects were correctly identified as infected
  • Pre-Test Odds are the subjective probability of the presence of the virus, before the test. For example, the patient shows COVID-like symptoms, or the surface is a high-touch, high traffic area in a community that has a known outbreak.

 

 

How accurate are the current test results?

If you could achieve 100% true positives and true negatives, you would have the perfect test. Yet no test gives a 100% accurate results. So tests need to be evaluated to determine their sensitivity and specificity, ideally by comparison with a “gold standard.” But there is no clear-cut “gold-standard” for COVID-19 testing, which makes the evaluation of test accuracy challenging. Instead, scientists use statistics. By repeating an assay, they are able to increase their confidence in the results. Using this approach, a systematic review of the accuracy of COVID-19 human tests reported that up to 29% of patients could have an initial false-negative result (21).

 

 

In fact, the accuracy of viral RNA swabs in clinical practice varies largely depending on the site and quality of sampling. In one study, sensitivity of RT-PCR in 205 patients varied, from 93% for broncho-alveolar lavage, to 72% for sputum, 63% for nasal swabs, and only 32% for throat swabs (22). Accuracy is also likely to vary depending on stage of disease (23) and degree of viral multiplication or clearance (24).

A 5-week study in over 53 Long-Term Care facilities shows that Enviral Tech’s surface tests have high sensitivity and specificity, as only 12 samples out of 2605 (0.5%) showed inconsistent results upon test repeat (download the white paper).

In contrast to PCR coronavirus surface testing, rapid SARS-CoV-2 tests that work like pregnancy tests detect antiviral antibodies by using a modified paper rather than a test tube. They are faster and potentially cheaper; however their very nature makes them less accurate than lab methods. Those tests are quick to manufacture and easy to use but have to be carefully designed and still need to be validated.

 

References

  1. WHO: Transmission of SARS-CoV-2: implications for infection prevention precautions. Scientific Brief - July 9 2020
  2. WHO: Criteria for releasing COVID-19 patients from isolation. Scientific Brief - June 17 2020
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  10. Five Things to Know about the Cost of COVID-19 Testing and Treatment. Kaiser Family Foundation 
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  26. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19)
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