We have done a commendable job with a small but highly efficient work force: Dr Sameer Bhati

Cases of false positives and false negatives have resulted in confusion as well as tragedies in some cases. Dr Sameer Bhati, Director, Star Imaging and Path Labs explains the significance and implications of these terms to Akanki Sharma and also the measures that need to be taken to minimise these errors.  He agrees that it’s true that India is still short of a proper ratio of healthcare workers compared to our vast population, but points out that it’s a proven fact that with this less but highly efficient work force till date we have done a commendable job

What are the possibilities for a COVID-19 RT-PCR test to come out negative even if a person is positive? Share a few case studies regarding the same.

Let us first understand the meaning of these terms:

1. True positive: A person with COVID-19 tests positive for COVID-19
2. False positive: A person without COVID-19 tests positive for COVID-19
3. False negative: A person with COVID-19 tests negative for COVID-19
4. True negative: A person without COVID-19 tests negative for COVID-19

(a) & (d) are desirable situations;        (b) & (c) types of testing errors

Now the combination of these four terms are used to define four new terms:

Accuracy =    (true positives + true negatives)/ all results

Precision =    true positives / (true positives + false positives)

Sensitivity =   true positives / (true positives + false negatives)

Specificity =   true negatives /(true negatives + false positives)

Generally, for RT-PCR Test:

• Sensitivity =80 per cent
• Specificity =90 per cent

By this way we can say that through RT-PCR test, there’s a chance of 10-20 per cent that the result comes out as COVID-19 negative even if a person is having the said disease.

 Here are some case studies to illustrate these points.

1. Recent death case of MAMC resident doctor where in he was tested through RT-PCR as negative on two occasions before he succumbed.
2. A 34-year-old man admitted to the Wuhan community hospital, tested negative for four times but only after CT, he was confirmed for COVID-19.
3. Aishwarya and Aaradhya Bachchan were also tested negative initially before turning positive with the same testing.
4. Similarly, In Maharashtra’s Governor house, 16 employees were also tested negative at first instance only to turn out as positive on subsequent occasion.

Tell us the various reasons behind this and what precautions should be taken to prevent it?

The reasons could be as follows:

1. Technical pitfalls related to processing techniques
2. Sample from upper respiratory tract may come out as negative
3. False negative result may come out because of mutations in primer and probe target regions in the SARS-COV2 genome
4. Errors related to Laboratory practices and personnel skills
5. Errors in sampling procedures
6. Timing for peak viral loads during the infection

These are the precautions that can be taken:

1. Multiple target gene amplifications could be used to avoid invalid results
2. To use different specimens types i.e. stools, blood besides respiratory specimens at different stages.
3. Sample should be obtained through a proper swab
4. Sample should be reached to the Lab ASAP
5. Sampling should follow all Guidelines designed by ICMR

Is this a common issue faced by all diagnostic companies globally? If yes, where does India stand in comparison to those?

False negative results are part of any testing technique and similar has happened with this test. So yes globally all the diagnostic companies are too facing the same issue.

In India we are facing little higher issues in comparison to the US and the European counterparts as it is a new technique for us. Plus there is a patient related factor as well as skill related factor

How can the credibility of RT-PCR tests be maintained in such a scenario? Antibody tests have also been found to come up with unreliable results. How do you see this?

To minimise the false results, combined efforts are needed. Diagnosis should be made concomitantly based upon the clinical features, RT-PCR and CT features suggestive of SARS-CoV 2. There should also be up-gradations of skills.

According to an author in a study published in the journal Annals of Internal Medicine, “A negative test, whether or not a person has symptoms, doesn’t guarantee that they aren’t infected by the virus.” What’s your view on this? Give reasons to support your answer.

Yes I fully agree with the statement for these reasons:

Firstly, sometime in the early phase of infection test may show negative result as seen in case of Aishwarya and Aaradhya Bachchan including Maharashtra Governor house employees.

And secondly, in some countries including India because of BCG immunisation and many other related factors, people might have developed some immunity because of which patients might not develop COVID-19 symptoms or may show only mild symptoms. Even then also patients might be harbouring the infection.

Do patients volunteer to enquire about the authenticity of the tests? What information do you share with them to satisfy their queries?

Yes patients do that. It comes under their patient rights. We share information regarding testing procedures, sample collection, detailed printed reports, and any issues related to COVID-19 or its treatment directions.

Why should diagnostics labs be more transparent about sharing the data related to shortcomings of the test? Are you doing it at your lab? If yes, how?

It is necessary for labs to be transparent because more accurate and authentic data will come up. Also, any abnormalities and technical issues could be addressed. A better picture of the disease spread could be estimated. Data can be analysed and better planning could be done and lastly, it helps to reduce the false negative results too.

We normally follow these procedures:

• Each and every data is shared with ICMR and government agencies
• Any new finding, is immediately rechecked and informed to ICMR
• Data is also used to publish research papers in reputed journals so that findings will remain in public domain to be used by the others in future
• We commonly discuss our findings and data trends over webinars and expert discussions

With India already being short of doctors, nurses and paramedics now, lakhs of COVID-19 tests are being conducted in a day. If testing too faces an issue of reliability, how do we expect to prevent the spread of this pandemic even amidst lockdown being imposed in many parts of the country, though a race for a vaccine is going on across the world?

It’s true we are still short of a proper ratio of healthcare workers compared to our vast population. But it’s a proven fact that with this less but highly efficient work force till date we have done a commendable job.

Reports with false negative results have many reasons as mentioned above but to minimise it we are now using other techniques together as previously mentioned, so that highly accurate results can be made out.

We are now in the stage of Unlocking. In spite of that, lockdown has been extended in some of the areas. More than 100 top companies at the international level are working over the vaccine and some of them are now into the final stages of developing it even including many from India. We are very positive on the vaccine front and are sure that there will be good news in a few days.

But we still cannot leave testing and social distancing practices. We are getting closer every day to the understanding of this virus behaviour and even hopeful with its vaccine, our testing abilities and accuracy will surely enhance.