The curious cases of the false-negative RT-PCR tests

I find it unusual. I have returned to Delhi, and even after two days my landlady has not paid me a visit. She is one warm woman, and perhaps needs someone to listen, and so she often walks up to my apartment when I return from work. I go down the stairs and knock. Her son opens the door. I gather a few parcels that are left by the delivery person and ask for his mother. “She’s not well, and the symptoms look like COVID,” he says. They have got her tested and the reports are expected.

Two days later I call up and I find her phone switched off. Concerned, I call up her daughter-in-law. She has tested negative, she tells me, and I heave a sigh of relief. “But her symptoms continue,” I am told. I guide her, and as I am about to end the call, I am told that my landlady’s son has tested positive for coronavirus! “There is no way your mother-in-law can be negative, treat her as COVID”, I urge her.

The next Sunday, my husband calls up from home complaining of a really bad sore throat. It is COVID, he is convinced. He stays back home and isolates himself from the others. But a day later he tests negative. The symptoms continue, and he now complains of lethargy and body ache. He has been completely vaccinated so perhaps the symptoms are mild. The house-help is told to stop coming, just in case. Maybe you tested too early, I say. So a repeat test is done 3 days later. Again negative. But by now, my eighteen-year-old niece who is staying with him starts coughing badly and develops a high fever. This is now suspicious. We wait for a day and then get her tested. She tested positive this morning. Which means the symptoms exhibited by my husband have to be COVID, despite two negative tests.

It is the same story at work. The lab is cramped with equipment, and there is only one small cubicle available where staff are permitted to eat. People who design spaces in government buildings never think of comfort of the personnel. So everyone had been eating lunch together. That is where the masks come down simultaneously. One faculty member tests positive for COVID. And everyone is in a state of panic. Some of them are exhibiting symptoms, which in this pandemic, should be COVID unless proved otherwise. But all six of them test negative. I’m not sure, and keep my mask up diligently.

We didn’t hear of so many false-negatives in the last wave. The real-time reverse transcription-polymerase chain reaction (RT-PCR) like any other investigation, is definitely not foolproof. All COVID tests have some degree of false negativity. The SARS-CoV-2 RT-PCR detects viral RNA and is highly specific (99-100%). This means that if you are reported as positive it is almost certain that you have been infected by the virus. The sensitivity of these tests is not uniform and is lower (ranging from 65-80%), even when properly sampled. Which means that even if you have a negative test result, there is a chance that you might still be harbouring the virus.

What are the factors which can lead to false negatives?

The three top reasons are the quality of the sample sent, the timing of the testing and the viral load.

There are clear guidelines given of how to collect and transport these samples. Unfortunately, given the unprecedented load of patients who are turning up for testing, I am not sure that the people who are given the responsibility of collecting the samples are actually properly trained. I have encountered people who have told me that the swab was collected from the anterior nares and not the pharynx. I once saw a health care worker ask a man why he had turned up for a test without having symptoms. When told it was because he needed a negative report in order to travel on a flight, the man was reassured that the swab would be inserted superficially as it didn’t make a difference. Attitudes like this could make a world of difference to how the virus spreads. The site of sample collection matters, as does the method of transport.

When you get tested, makes a difference to the results you receive. When the test is done within the first four or five days of exposure to a positive patient, it is more likely to be negative. You might come away complacent that you are negative and end up being a source of infection to others. The virus is most contagious 48-72 hours before the symptoms show up. If you are symptomatic, it means you could have been infected anywhere between 5-14 days ago. This is the incubation period of the virus. A good time to get tested would either be 5-7 days after known exposure, or when you are symptomatic. One is infective to others up to 14 days of the exposure, so it is best to keep oneself quarantined for that duration.

The RT-PCR test depends on the viral load. So if you have been infected but if you have a low viral load, then your report will be negative. This could happen too early in the infection or too late in the infection cycle. We still don’t know the impact of previous vaccination, but that could be a factor.

As far as the question of whether the test is detecting the newer variants is concerned, experts in India say that the test is capable of detecting most mutations. The UK, Brazil, South Africa and double mutant variants have been detected by the present kits.

What are the consequences of these false-negative tests? Horrendous. On the ground level, these translate to spreading the infection because of the complacency of being negative. I know of entire car pools which have been infected because the first report was negative, and the second test turned positive. So it is prudent to wear your mask, stay safe and let others be safe. There is no other resort we have.

But there is worse. We received a call from a distant elderly relative in Bihar who had breathlessness and an abysmal oxygen saturation level. He has tested negative. But his wife has tested positive. We try to get him admitted into a hospital, but they are refused. The oxygen cylinders have been reserved for COVID patients, and he is not COVID positive. A similar story of a retired nurse who hasn’t been admitted to the hospital where she worked all her life reaches my ears. They can’t admit her as she hasn’t tested positive.

I’m wondering about the state of patients who have ailments other than COVID. What is the penalty they are paying for this pandemic?

This pandemic is a tragedy of unprecedented magnitude. The state of affairs on ground zero are horrifying. We are desperate to see the light at the end of this long tunnel. Suddenly the only thing which matters is survival.

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