All You Need to Know About COVID Tests
Sometimes reports about the accuracy of COVID testing results just don't make sense. The Delhi Health Minister, Satyendar Jain tested negative for COVID. But as his symptoms persisted, he was tested again. And he tested positive during the third time. How do you make sense of these test results? A HE report.
Under normal circumstances, testing is a stressful affair. In times of a pandemic, it's even more troublesome and frustrating for patients as well as healthcare providers.
Nadeem Ahmed, a primary and emergency care physician at PonMalligai Hospitals, Adambakkam, Chennai has a lot to say about COVID testing.
"As Indians, we have learnt from a very young age to do more with less. The same goes for how doctors prescribe COVID19 tests. We continuously battle for a middle ground between over-testing and under testing," he says."Following the latest guidelines and protocols has eased this battle to an extent. From our experience, we have found out that the symptomatic patients who reach out to us are more accepting of the notion of testing if we recommended the same after extensive history taking and examination," he adds.
The real challenge for physicians lies in persuading the potential and confirmed contacts of COVID +ve patients to undergo rapid antigen or RT-PCR testing. What concerns doctors like Ahmed is not that they would be positive, but that they could be potential superspreaders who could make a lot more high-risk individuals critically ill if not forced into self-quarantine.
"The time spent in convincing such reluctant contacts to test themselves or better restrict themselves to home quarantine for the prescribed period takes a considerable amount of our time away from active practice. It would benefit us immensely if baseline awareness increases amongst people," explains Ahmed, who also works as a consultant to health tech startups.
Accuracy of COVID tests
During the ongoing COVID-19 pandemic, there is a lot of buzz regarding the possible errors in diagnosis with RT-PCR based tests around the world. To understand the seriousness of these errors, we need to understand the nature of different types of errors.
"When a new testing kit is created and launched, as in case of COVID-19 condition, its accuracy cannot be precisely predicted. The testing kit works differently when applied in the real world. These conditions might enhance the likelihood of errors due to many unforeseen events," says Subash Sonkar, Scientist-II, Maulana Azad Medical College, University of Delhi.
Sonkar points out that in reality, experts encounter four types of scenarios:
True positive: A person with COVID-19 tests positive for COVID-19
False-positive: A person without COVID-19 tests positive for COVID-19
False-negative: A person with COVID-19 tests negative for COVID-19
True negative: A person without COVID-19 tests negative for COVID-19
So, what do terms like accuracy, precision, sensitivity and specificity mean?
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.
"Different values of the sensitivity of RT-PCR tests have been reported in different parts of the globe. According to one analysis with 51 people in China, up to 29% of people with the coronavirus tested negative. Studies in the US returned multiple values – it was 95%, sometimes 85%, and even 75%," says Sonkar.
Dr Arjun Dang, CEO, Dr Dangs Lab also admits that sensitivity and specificity holds a lot of relevance in the accuracy of the test. "Sensitivity always depends on the lower detection limit of the virus. Majority kits offer a sensitivity of about 70 per cent, with a very low detection limit. There are kits with fairly high detection limit but a sensitivity of 99%. Specificity has never been an issue with PCR kits because all of them are highly specific."
Dang points out that when you say sensitivity is 70 per cent, it means that a certain per cent of samples would be tested negative. The reason for that would be the exact viral load in the COVID patient. RT-PCR tests authorised by ICMR are qualitative, which means you don't get a value, but a screening as a positive or a negative. Viral shedding is the immunity of the body that is fighting against the load or potency of the virus. If you test positive on the first of the month, after the first week, we have seen the body's immunity fights the infection and reduces the viral load. So the positives can convert into a negative within a week. Some people may take up to two-three weeks. The false-negative, in that case, would be attributed to the low viral load in the patient," he explains.
What about false positives? Dang says that RT-PCR test tries to detect the RNA or the gene that represents the virus in a sample. "The RNA cannot just come out of anywhere. If it's detected, it means that it has been present in the sample. There could be labelling or transcription errors, but once the sample is inside the building, a false positive is not at all possible."
ICMR has recently suggested the states to allow all medical practitioners including "private doctors to prescribe COVID-19 tests to anyone fulfilling the criteria for testing".
"RT-PCR tests are considered the gold standard for detecting COVID 19 and excellent in ideal conditions.But in the real-life, testing conditions and process are far from perfect, and accuracy suffers," says Dr Chaitali Nikam, Deputy General Manager, Thyrocare Technologies Limited. "Still, it's unclear about the false positive rate, but the clinical sensitivity of RT-PCR tests ranges from 66% to 80%. That means nearly one in three infected people who are tested will receive false-negative results," she explains.
What is the sensitivity and specificity of the COVID19 RT-PCR test used in India? "It's above 90 per cent for the COVID-19 RT PCR test kits used in India," she adds.
Obtaining the Right Quality Swab
Nikam also adds that there are several difficulties in obtaining the right quality swab.
"Quality of collection kit, trained resources, bottlenecks and high costs are problems associated with collection of nasopharyngeal (NP) and oropharyngeal (OP) swabs used in COVID testing. If not done correctly, it can injure the person and cause bleeding. It can also provoke sneezing or coughing, generating aerosols with infectious virus particles from a positive patient, exposing the worker to a potential infection. Swabbing the nasopharynx is an invasive and almost blind procedure. An NP swab is passed along the floor of the nasal cavity up to the back wall, twirled for a few seconds then drawn out. This procedure is not always agreeable for the patient or the health worker.
Likewise, the OP sample, which is collected from the back of the throat, can also induce gagging and coughing. A diverged nasal septum, tumours or nasal polyps can hamper collection. If swabs are not of the right type, they can increase discomfort to patients and also affect test results. For example, a cotton or calcium alginate tip interferes with the polymerase chain reaction (PCR), and a flexible shaft is required to get to the nasopharynx," she explains.
There are variances in sample collection. "OP swabs are less sensitive compared to NP. Changes in the time of collection also affect test performance as it depends on the viral load during the test. The procedure requires a skilled and dedicated health worker and assurance of their availability. Otherwise, the shortage of resources is typical during pandemics," she says.
She also adds that healthcare personnel change their entire PPE gear, priced at nearly Rs 500/piece, between swab collections. Irrational use of PPE adds to the tons of biomedical waste being generated. On the other hand, some centres don't have sufficient funds to afford good quality and adequate PPE for frontline staff.
How to Educate Citizens
How can the country and labs educate citizens on inherent sensitivity, false positivity, false negativity so that patients who get tested are aware of these factors before taking the test? Nikam adds that its a difficult task but manageable.
"Each laboratory must write about it in the report format under headings like indications, comments or remarks along with references. People need to pay attention to this information before comparing one report to another.
Instruction should be given to the patient by swab collection technician in this regards beforehand collection of the sample or during filling Sample Requisition form. Publicity by the media may play a crucial role in this for mass communication," she adds.
Other Testing Options
In the chance that someone shows strong signs and symptoms of COVID 19, but RTPCR is repeatedly negative, what are the other available testing options?
"RT PCR is considered to be the gold standard for active infection. Radiological findings can be helpful, but it will indicate Influenze-like illnesses (ILIs,) not COVID. Rapid Antigen test can be checked for along with an antibody test. Anyone of the tests above indicates active, or past infection & PCR inhibition can be ruled out," concludes Nikam.
Antibody tests
What about antibody tests?
"When someone is infected with any infectious agent, the body's immune system produces antibodies to fight against the infection. Same way COVID -19 infection triggers our immune system to produce antibodies to fight against it. These antibodies last in the body from a few months to years, and the detection of such antibodies provides a clear picture of your current immune status.
"Negative antibody test indicates no exposure so far for Covid-19. Currently, ICMR approved IgG ELISA tests and also Total antibody on the automated platform by ECLIA technology. As long as you have a high level of antibody, you are immune to reinfection. However, still, research is going on for the duration of protection and secondary infection," she concludes.
Healthcare System needs Cooperation of Patients
"People have genuine concern about false-positive and false-negative results. One of the reasons could be reasonable fear associated with the cost of treatment and taboo associated with social isolation. But false positive and false negative results are not equally crucial during pandemic times provided enough resources available for follow-up assessment or tests. People should not panic in case of false positive as they will undergo a second round of testing. What people should understand is that an outbreak or pandemic happens without any prior notice and preparation and development of testing kit take time. To counter pandemic, we need to cooperate with the administration, and we should act calmly in case of any error," says Peeyush Prasad, a biomedical researcher.
