RT-PCR (reverse polymerase chain reaction) test is used to rule out the presence of SARS-COV-2 infection in at-risk individuals, such as medical staff and outpatients. This is why it is so important to know how the predictive value of this test changes over time for exposure to symptoms.

This is especially important when the results of RT-PCR tests are used to make decisions about providing protective equipment to treatment workers or returning them to work.... Stay tuned to GCORP.

RT-PCR test (reverse polymerase chain reaction)

Sensitivity and specificity of PCR-based tests for SARS-COV-2 are rarely known.. Also, the effect of having a "window period" (window period) after being infected with the virus, which is more likely to be a negative result, is not very inaccurate..

correct test SARS-COV-2 and the subsequent use of protective equipment in the care units is very important because it prevents nosocomial transmission as well as person-to-person transmission of the infection. However, many hospitals have a severe shortage of laboratory equipment for SARS-COV-2. encounter According to the guidelines provided by the Centers for Disease Control and Prevention, the sick person should remain in quarantine for 14 days (following the principles of proper ventilation, the risk of infection is also minimized during this period... (2); however, this action is difficult in hospitals that have limited resources.

With the increased availability of RT-PCR testing, its use to rule out infection in medical staff has also increased.... This action is being taken to preserve valuable labor and scarce protective equipment.... When the test results of the treatment personnel are negative, they are allowed to return to work.

In the case of patients, when the test is negative, the precautions and ventilation restrictions applied are lifted. If the RT-PCR test is performed in the window period and the negative result is interpreted as the absence of the disease, it can lead to preventable transmission of the disease.

It is very important to know how the predictive value of the RT-PCR test is affected by the time between the first exposure and the onset of symptoms.. This prevents false confidence about the negative results of the tests performed in the early stages of infection.. The aim of our study is to estimate the negative results after exposure on false days..

The probability of a false negative result of the PCR test in SARS-COV-2 positive patients, days after exposure

4 days before the onset of symptoms (day 5), the probability of a false negative result in an infected person decreases from 100% (95% Cl, 100% - 100%) on the first day to 67% (Cl, 27% -94%) on the fourth day.. However, there is no certainty in these figures.

On the day of symptom onset, the mean false-negative results were about 38% (Cl, 18%–65%) (Fig. 2, top) ... This value increased to 20% (Cl, 12%–30%) on day 8 (three days after symptom onset) and then gradually increased from 21% (Cl, 13%–31%) on day 9 to 66% (Cl, 54%–77%) on day 21. found.

Probability of infection after negative RT-PCR result (which is obtained by 1 minus NPV)

Note: NPV is the same as negative forecast value.

When converting these results to the probability of post-test infection, a negative result on day 3 reduces our estimate of the relative probability that the patient is infectious to only 3% (Chlor, 0% to 47%) (i.e., the relative probability that the subject is infectious drops from 11.2%.. down).. Performed first are more useful on the day of symptoms, because in them the relative probability of the patient being infectious decreases by 60% (Cl, 33%-80%).

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The difference in the probability of infectiousness after a negative result of the RT-PCR test based on the probability of being infectious before the test

The probability of infectiousness after the test in a patient with a negative RT-PCR result varies depending on the probability of infectiousness before the test (this topic explains the probability of infection based on the severity of exposure to clinical symptoms).

Assuming a high probability of infectiousness before the experiment (which was 4 times higher than that observed in a cohort study), the probability of infectiousness after the experiment and 8 days after exposure was at least 14% (Cl, 9% - 20%) (Figure 3)... (1.2% [Cl, 0.7% - 2.0%]).

Discussion

On the day of symptoms, the average rate of false negative results was about 38%....this value decreased to 20% on the eighth day (three days after the onset of symptoms) and then increased again...so that on the twenty-first day it reached 66% from 21% on the ninth day.

The rate of false-negative results was at least 8 days after exposure (i.e., on average, three days after the onset of symptoms). Therefore, perhaps the best time to test to minimize false-negative results is on the eighth day after exposure.

Since the outbreak, concerns have been raised about the low sensitivity of RT-PCR tests (18).. 1 study showed that the sensitivity of this test may be as high as 59% (19).

We have developed a publicly available model that provides a reasonable framework for estimating exposure times for these experiments. This model will be updated as more information becomes available.

RT-PCR tests performed to detect SARS-COV-2 have low diagnostic value if performed immediately after exposure to the infectious agent.. The reason for this is the existence of a time interval between being infected with the virus and being able to detect it by RT-PCR, which is also seen in other C2 and C2 viral infections..

Our study considers this time interval to be 3 to 5 days....Also, our recommendation is that the mere negative test result and the absence of symptoms during the window period cannot be a reason to stop preventive measures (such as contact restriction or quarantine). be.

Although the rate of false negative results reaches its lowest level at about 1 week after exposure, it is still high (21%)....Possible mechanisms leading to the high rate of false negative results include individual variability in viral shedding and sampling methods.
One of the debated issues is whether serial tests have an advantage over a single test. However, this claim cannot be defended until the root cause of the above false negative results is determined.

For example, if the reason for the high rate of false-negative results is due to individual variation in viral shedding, multiple tests are not advantageous over a single test.

Although we are aware of small-scale studies (no large-scale studies), some preliminary reports indicate that the results are not independent.. For example, a case report shows that in a person whose infection was confirmed by radiological findings and RT-PCR was performed on a sample obtained from tracheal secretions, the result of RT-PCR performed on samples obtained from the nasopharynx during the clinical course of the disease was negative. (6).

In general, it can be said that more studies should be done to determine the operational weakness of the RT-PCR test in identifying SARS-COV-2 infection... The relationship between the false negative result and the rate of infection (Infectiousness) is unclear, and patients whose nasopharyngeal sample test results were negative, regardless of the case report, are less likely to transmit the disease to others.

We noticed a re-emergence of false negatives from day 9 post-exposure.. Obviously some of these false negatives were not really false negatives, but still counted as no infection. According to what was mentioned, the interpretation of the test result and determining the future clinical course depends on the purpose of the test.. If the purpose of the test is to decide to remove the person from quarantine, false negative results may be detected.. Score, more studies are needed. be.

Since antibodies are also produced during the course of infection, a combination of antibody testing and RT-PCR may be effective in screening asymptomatic individuals or individuals with unknown exposure.

Our study has several limitations... There was considerable heterogeneity in the studies on which our analysis was based... However, when we performed a sensitivity analysis and excluded each study in turn, we found that no study was particularly effective and the results remained largely unchanged.

Sampling methods were different in different studies (oral or pharyngeal samples compared to the nasopharynx) and some studies also stated without mentioning more details that the samples were taken from the upper respiratory tract (they did not mention the exact place of sample preparation).... For this reason, it is not possible to count on various sample collection methods.

Many studies examined samples at the time of onset of symptoms (not at the time of exposure), which caused great variability in the estimates made in the first days after exposure. Our model is only applicable to a known exposure and is not suitable for repeated exposures, such as the daily exposure of health care workers-2 known SARS.VCO patients>

Finally, most studies defined true positive cases as at least one positive RT-PCR test, meaning that people who never tested positive were not considered patients.... This issue can cause the true false negative rate to be calculated lower than its true limit.

Two studies included suspected cases based on clinical findings and epidemiologic features, whose serologic or RT-PCR tests were never positive... Since the criteria for fever, respiratory symptoms, and imaging findings are nonspecific, there is a possibility of misclassification of patients.. In this case, some suspected cases are indeed true negatives.

We believe that the effect of this confounding factor is very small because removing these studies from the analysis did not change the primary result.
In summary, it can be said that caution should be used when interpreting the results of the RT-PCR test for the diagnosis of SARS-COV-2 infection, especially when these results are considered as the basis for the removal of the imposed restrictions (which were aimed at reducing the spread of the disease).

If the clinical suspicion is high, the possibility of the person being infectious should not be rejected based on the RT-PCR result alone, and the clinical and epidemiological conditions should also be taken into account. In many cases, the time of exposure is not known and the test is performed based on the time of onset of symptoms (the eighth false negative value after reaching the lowest day of contact, the lowest false negative value on the day of exposure... three days after the onset of symptoms)...

Physicians should wait 1-3 days after the onset of symptoms to minimize a false negative result....Further studies are needed to determine the characteristics of this test and identify more sensitive methods....This discussion deserves extensive investigation and research....For more information about RT-PCR or its false result, contact your doctor.. LLC makes an appointment online.

Source: Thelancet and idsociety

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