Tests may miss more than 1 in 5 COVID-19 cases
06 June, 2020
A team from Johns Hopkins Medicine has discovered that PCR-based tests for SARS-CoV-2 have a false negative rate of at least 20%, based on the time of testing.
Nearly all tests for the novel coronavirus involve going for a swab from the trunk of the nose or the throat for genetic analysis.
This analysis runs on the laboratory procedure called reverse transcriptase-polymerase chain reaction (RT-PCR), which converts genetic material from the virus (RNA) to DNA before amplifying it. It allows the detection of genetic material specific to the SARS-CoV-2 virus, confirming a diagnosis of the associated disease, COVID-19.
Although serological, or antibody, tests are also available, these typically serve to verify a past infection in people who've since recovered from COVID-19, instead of to detect an active infection.
There's been much discussion about the accuracy of antibody tests, with manufacturers even withdrawing some such tests due to concerns about their reliability. A fresh analysis shows that the accuracy of RT-PCR could also be under question.
Scientists from Johns Hopkins Medicine in Baltimore, Maryland, have displayed that as many as 1 in 5 RT-PCR tests for the coronavirus may produce false negatives, incorrectly informing a patient that they don't have a SARS-CoV-2 infection if they actually do.
Estimating sensitivity
Since the start of the coronavirus outbreak, RT-PCR has had routine use as a diagnostic tool. However, the accuracy of the technique in detecting SARS-CoV-2, and particularly how this pertains to the amount of time since the infection, is unclear.
Understanding the accuracy of the test is essential because the results frequently donate to important decisions, such as for example whether to allow healthcare workers to return to work.
Incorrectly telling a person working on the frontline that they don't have a SARS-CoV-2 infection and may return to work could lead to further spread of the virus. Additionally, the info from testing also informs the decisions of governments regarding the lifting of restrictions.
To estimate the rate of false-negative tests for the coronavirus, the researchers behind this study searched the literature on this issue. They included studies which used an RT-PCR-based test to find SARS-CoV-2 in samples collected from the upper respiratory system and that also reported enough time since symptom onset or contact with the virus.
They discovered seven studies in total, which included data from 1,330 patient samples, including inpatients (people in a healthcare facility) and the ones managing their symptoms at home.
The optimal time for testing
Their analysis showed that the probability of a false-negative result varied based on enough time since infection.
It would appear that the virus is not detectable soon after infection. On the first day of infection, the likelihood of missing a diagnosis, i.e., a false-negative result, was 100%.
At day 4 after contact with the virus, the likelihood of a false-negative result seems to reduce to 67%. By day 8, it decreases to 20%, beginning to increase again afterward. By 3 weeks postexposure, the opportunity of a false negative result reaches 66%, the authors estimate.
The results indicate that the virus is difficult to detect by RT-PCR in the times rigtht after infection, suggesting that this testing route offers limited value during this period (3-5 days postinfection).
The authors recommend against making major decisions, such as removing personal protective equipment (PPE) or ending quarantine, predicated on results obtained in this period. Similarly, the test offers limited value a long time following the initial exposure.
They say that 8 days following exposure, which is roughly equivalent to 3 days following onset of symptoms, may be the optimal time for testing.
At this time, the risk of obtaining a false-negative result reaches its lowest, although there continues to be a 1 in 5 potential for obtaining such a result.
The authors say that the reason why for such a high rate of false negatives, beyond technique-associated error, include dissimilarities in the quantity of viral genetic material in people’s samples and distinctions in sample collection techniques.
Exercise caution
Based on their findings, the authors say that it is necessary to exercise caution when interpreting the results of RT-PCR tests for SARS-CoV-2, particularly if the test took place early on in the course of infection.
If a person has symptoms constant with COVID-19 but tests negative, the authors advise not ruling out infection and carefully taking into consideration the “clinical and epidemiologic situation.”
They also say that a combo of antibody testing and PCR-based methods could possibly be useful for patients who no longer have symptoms.
“Clinicians should consider waiting 1 to 3 days after symptom onset to reduce the probability of a false-negative result.”
- The study authors
The authors do note some limitations with their study, like the fact that the studies that they analyzed had different designs. They state that further studies are essential to characterize the performance of RT-PCR tests for SARS-CoV-2 better and to identify alternative, more sensitive approaches.
Source: www.medicalnewstoday.com
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