Can You Be COVID Positive Even if Your RT-PCR Test Says Negative?

Can new variants identified in the country escape RT-PCR tests?

In spite of having all the telltale symptoms of COVID, some people's RT-PCR COVID test results have been coming back negative.

COVID was then detected in other follow-up tests including CT scans, but only after their health deteriorated significantly.

The RT-PCR test is considered the gold standard for testing corona infection. So much so that Negative RT-PCR test results are mandatory for admission in many states.?

With the surge in corona cases in the country, the number of people who have done these tests has also increased. And at this point in the second wave, false negatives of COVID tests can prove extremely damaging.

Can RT PCR report negative even if they have been infected? What to do if you have symptoms of COVID, but the RT-PCR test report is negative? Can new variants of COVID slip through the RT-PCR test?

What causes a false negative?

Experts talk of many possible reasons for this.

• No test is a 100 percent accurate.
• Timing of the COVID test: In case of coronavirus, incubation period (time from exposure to virus to symptom onset) is longer, it can be 2 to 14 days. Therefore, doctors recommend getting tested 5 or 6 days after the exposure.

“It has been seen many times that people come in contact with a positive person and get the test done immediately. There is a time for this, if we have come in contact with an infected person, then the test should be done after about five days.”

Sameer Bhati, Director, Star Imaging & Path Lab

• Viral load may be low: It may also happen that if the viral load in RT-PCR test is not that much, then the test report may come back negative.
• If the sample is not taken properly: An error in results can occur if the swab stick is not inserted properly why collecting the sample.
• Issues in the storage and transportation of samples: Apart from the way the samples are collected, the way they are transported and stored can also affect the results.

“False negatives can also occur when the sample is not properly transported to the lab because it has to be maintained at a particular temperature.”

Sameer Bhati, Director, Star Imaging & Path Lab

Sampled labelling or hasty testing: With the increasing cases of COVID cases in the country, the number of people getting tested is also increasing, adding to the increasing burden on test centres.

• Long lines and the need to get through the tests quickly could lead to hastiness and errors in results.

“The RT-PCR result depends on several factors such as adherence to the entire procedure, sample type, sample collection time after symptoms, age of the patient. All these procedures require extreme caution.”

Dr Anupa Dixit, Lab Director of Suburban Diagnostics

Why are false negatives a matter of concern?

A false-negative test report may delay the treatment of patients. Waiting till a patient’s condition deteriorates from bad to worse can lead to the requirement of expensive treatment.

A false negative result may cause infected individuals to delay isolating themselves, facilitating further COVID transmission in the meantime.

It is very likely that such individuals could be “super carriers” of the disease, so one needs to be especially careful.

Are the new variants slipping through the RT-PCR tests?

One hypothesis that some expert have for the false negative results is also that it could be associated with new variants of the COVID virus.

They wonder if the changes in the virus make it difficult to identify them with standard RT-PCR tests.

According to the American Food and Drug Administration (US FDA), false negative test results may occur because of the genetic variants of SARS-CoV-2 that are routinely generated.

“In the case of new variants, it is definitely a matter of concern that these mutations may affect the current RT-PCR test in identifying the virus.”

Dr Anupa Dixit, Lab Director of Suburban Diagnostics

However, such concerns have been denied by the Center amid concerns of failure of RT-PCR testing. The central government said on Friday, 16 April that so far the Double Mutant or other variants identified in the country have not escaped the COVID tests.

“RT-PCR test is gold standard, we measure two genes or more, therefore, there is no chance of missing detection of any mutant.”

Dr Balram Bhargava, Director-General, ICMR

This is because RT-PCR tests used in the country target more than two genes, and according to the FDA, tests that use multiple genetic targets for final results are less likely to be affected by genetic variants.

Dr Anupa Dixit says, "the mutations are usually known to occur in the spike protein region and the detection can be missed in case of RT PCR kits that are meant to pick up Spike protein only."

She goes on to add, "It has been seen that the B.1.1.7 variant has 2 deletions at positions (69 and 70) which cause S-gene target failure (SGTF) in at least one RT-PCR based diagnostic assay."

“But in the case of our kits, while the variants with positions 69 and 70 will give negative results for the S-gene target, the other two will give positive results for the target and thus the final result will be positive.”

Dr Anupa Dixit, Lab Director of Suburban Diagnostics

The second thing to note is that the new variants identified in the country have been done so using genome sequencing of positive samples.

Anupa Dixit explains that the detection and confirmation of variants is possible only by genomic sequencing of viruses, which is being done by central institutions.

That is why the Center has expressed concern that many states have not sent samples for genome sequencing with clinical data of COVID positive people, while it has been advised to do so.

What should you do if your test comes back negative, but you have symptoms of COVID?

In such a situation, Sameer Bhati advises getting tested again.

If you get a negative reading in spite of having clear symptoms, it is important to inform the doctor about the symptoms.

The doctor can then, based on his discretion, recommend other tests like CT scan, and start the necessary treatment based on the symptoms.

• Isolate yourself if you have come in contact with a COVID positive person or are showing signs of having caught the infection.
• Keep an eye on your symptoms, including new symptoms.
• Keep the doctor informed of your condition while in isolation.
• Keep an oximeter with you and note the reading at least twice a day, if the oxygen level falls below 94, contact the doctor.
• If you still have symptoms, then do the test again after three days.
• If the doctor says, get a CT scan done.
• The doctor may also ask for some additional blood work.

Finally, the same thing that has been said since the beginning of the pandemic, follow COVID-appropriate behaviour of wearing masks, physical distancing, maintaining hand hygiene and avoiding crowded places.

Even if you have been vaccinated, have recovered once already, or your test results come back negative, do not violate the COVID protocol in any case.

For the time being, as we wait for this wave to pass over, this is what we can do to protect ourselves, our loved ones and others.

(This story was first published on FIT and has been reproduced with permission.)