Tests may miss more than 1 in 5 COVID-19 cases
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%, according to enough time of testing.
The majority of tests for the novel coronavirus involve taking a swab from the back of the nose or the throat for genetic analysis.
This analysis uses a 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 confirm a past infection in persons who've since recovered from COVID-19, rather than 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 new analysis shows that the accuracy of RT-PCR may be under question.
Scientists from Johns Hopkins Medicine in Baltimore, Maryland, have shown that as much as 1 in 5 RT-PCR tests for the coronavirus may produce false negatives, incorrectly informing a patient that they do not have a SARS-CoV-2 infection if they actually do.
The details come in the Annals of Internal Medicine.
Estimating sensitivity
Since the start of the coronavirus outbreak, RT-PCR has already established 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 because the infection, is unclear.
Understanding the accuracy of the test is essential for the reason that results frequently donate to important decisions, such as for example whether to allow healthcare workers to come back to work.
Incorrectly telling a person focusing on the frontline that they don't have a SARS-CoV-2 infection and will go back to work could cause 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 discover SARS-CoV-2 in samples collected from the upper respiratory tract and that also reported the time since symptom onset or exposure to the virus.
They discovered seven studies altogether, including data from 1,330 patient samples, including inpatients (people in a healthcare facility) and the ones managing their symptoms in the home.
The optimal time for testing
Their analysis showed that the likelihood of a false-negative result varied according to enough time since infection.
It would appear that the virus isn't 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 appears to lessen to 67%. By day 8, it decreases to 20%, starting to increase again afterward. By 3 weeks postexposure, the chance of a false negative result reaches 66%, the authors estimate.
The results indicate that the virus is difficult to find by RT-PCR in the days immediately following infection, suggesting that testing route offers limited value during this period (3-5 days postinfection).
The authors recommend against making major decisions, such as for example removing personal protective equipment (PPE) or ending quarantine, predicated on results obtained in this period. Similarly, the test offers limited value a long time after the initial exposure.
They state that 8 days following exposure, which is roughly equal to 3 days following onset of symptoms, may be the optimal time for testing.
At this time, the risk of finding a false-negative result is at its lowest, although there continues to be a 1 in 5 potential for obtaining such an outcome.
The authors say that the reason why for such a higher 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 crucial to exercise caution when interpreting the results of RT-PCR tests for SARS-CoV-2, especially if the test occurred early on throughout infection.
If an individual has symptoms consistent with COVID-19 but tests negative, the authors suggest not ruling out infection and carefully taking into consideration the “clinical and epidemiologic situation.”
They also say a combo of antibody testing and PCR-based methods could be useful for patients who no longer have symptoms.
“Clinicians should think about waiting 1 to 3 days after symptom onset to reduce the likelihood 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 necessary to characterize the performance of RT-PCR tests for SARS-CoV-2 better and identify alternative, more sensitive approaches.
Source: www.medicalnewstoday.com
