Interpreting COVID 19 test results

A misinformation campaign on COVID 19 is spreading rapidly especially through social media platforms. There is indeed a lot of positive information as well which reaches out to people though this alternate media but there are more takers for negative & fake news which is really depressing.

At a time when social media is abuzz with the repeated tweets referring to a particular covid positive, the very credibility of our existing healthcare system is at stake. This has put a question mark on the competence and calibre of our doctors working at the forefront of COVID 19 epidemic. Unfortunate thing is that many reputed citizens also endorse such unscientific views on social media. As a public health specialist it is my foremost duty to talk about this deadly virus and the interpretation of its test results.

Infectious period
Length of time an individual can transmit the infection to others is not known precisely, but possibly up to 10-14 days. Reducing the contagious period is a crucial method of reducing overall transmission. Hospitalization, isolation, lockdown and quarantine are all effective methods. Anyone infected with the virus can infect even before the symptoms appear. Most carriers do not even show signs. Use of masks, covering our mouth and nose and even eyes with glasses (while going out) will help reduce the infection. The virus is present in the saliva, sputum and even in faeces of the infected person for the whole infectious period.

How do we get infected?
Transmission is mostly via droplets. This requires relatively close contact, less than 2 metres. Therefore it is recommended to use face masks and that we stay 1.5 metres away from each other in public gatherings. A study done in Hong Kong showed that social distancing can reduce the spread by 44 %.  Inanimate vectors of disease, in particular phones, door knobs and surfaces are potential sources for transmission, but not much is known about it. It is safe to sanitise our hands after touching doorknobs, lift call buttons and counters at public places.

How many we infect
                R0, pronounced “R naught,” is a mathematical term that indicates how contagious and infectious disease is hence it is an important marker to study the progression of a disease. Using the R0 value, the transmission rate of a disease or its decline can be calculated.The average number of new infections caused by a typical infectious person is between 2.2 to 3.1. In simple words, one infected individual on the average infects more than 3 people. By physical distancing, we can artificially reduce the actual transmissibility, thus slow the rate of infection.

Getting Infected twice
                Once we get measles, most of us acquire lifelong immunity. We hardly get measles again. Likewise, there is no evidence of reinfection with SARS-CoV-2 after recovery in humans. However, how long the immunity will last is unknown. The majority of COVID-19 cases are mild (81 %). About 15% need hospitalization and 5% require critical care. Healthcare workers are most susceptible. Among the general public, aged, in particular above 60 years of age and people with prior cardiovascular disease, hypertension, diabetes, and respiratory conditions have a higher risk. Most of the deaths are caused by respiratory failure or respiratory failure combined with heart damage. Leakage of fluid into the lungs, which inhibits respiration and leads to morbidity, is the primary clinical condition. At present, the treatment for COVID-19 is primarily supportive care, including ventilation if necessary. Several therapeutic trials are ongoing, and the results are awaited.

Interpreting a COVID 19 test result
Across the world there is a clamour for covid-19 testing, with Tedros Adhanom Ghebreyesus, Director General of the World Health Organization (WHO), encouraging countries to “test, test, test”. The availability of the complete genome of covid-19 early in the epidemic facilitated development of tests to detect viral RNA. Multiple assays with different gene targets have been developed using reverse transcriptase polymerase chain reaction (RT-PCR). These viral RNA tests use samples usually obtained from the respiratory tract by nasopharyngeal swab, to detect current infections. No test gives a 100% accurate result; tests need to be evaluated to determine their sensitivity and specificity. In case of coronavirus, RTPCR is still considered as the gold standard test as it even picks the minute bits and traces of the virus.

Sensitivity and Specificity
Sensitivity is the proportion of patients with disease who have a positive test, or the true positive rate. Specificity is the proportion of patients without disease who have a negative test, or true negative rate. These terms describe the operating characteristics of a test and can be used to gauge the credibility of a test result. They can be combined to calculate likelihood ratios that indicate the strength of a positive or negative test result. Positive likelihood ratios greater than 1 are progressively stronger, with 10 representing a very strong positive test result. Negative likelihood ratios less than 1 are also progressively stronger, with 0.1 representing a very strong negative test result. In the case of the nasopharyngeal swab RNA test for covid-19, the positive likelihood ratio is about 14, which is excellent. A positive covid-19 test result should be very compelling. The negative likelihood ratio is 0.3, which is a moderate result, but not nearly as compelling as a positive result because of the moderate sensitivity (about 70%) of the covid-19 test.

Interpreting test results
A single negative test result may not be informative if the pre-test probability is high. Interpretation of a test result depends not only on the characteristics of the test itself but also on the pre-test probability of disease. Pre-test probability is high in someone with typical symptoms of covid-19, high risk of exposure, working in a high prevalence region, and negative test results can therefore be misleading. When people fail to estimate the pre-test probability and only respond to a piece of new information, they commit a fallacy called base-rate neglect. It is therefore imperative that with strongly suggestive symptoms to self-isolate in line with guidelines for covid-19, even though his test results are negative. This case illustrates the fallacy of base-rate neglect; it can be tempting to trust the results of an “objective” test more than one’s own “subjective” clinical judgement. In general, during this pandemic, pre-test probabilities of covid-19 will be high, particularly in high prevalence settings.

Practical implications
While positive tests for covid-19 are clinically useful, negative tests need to be interpreted with caution, taking into account the pre-test probability of disease. Chinese handbook of covid-19 prevention and treatment states “if the nucleic acid test is negative at the beginning, samples should continue to be collected and tested on subsequent days.” False negatives carry substantial risks; patients may be moved into non-covid-19 wards leading to spread of hospital acquired covid-19 infection, carriers could spread infection to vulnerable dependents including health care workers. Clear evidence-based guidelines on repeat testing are needed, to reduce the risk of false negatives. Patients with a single negative test but strongly suggestive symptoms of covid-19 should self-isolate himself as per guidelines for suspected covid-19. Positive tests can be useful to “rule-in” covid-19, a negative swab test cannot be considered definitive for “ruling out.”

Conclusion

In light of the above facts, I request people not to heed rumors. Without ascertaining the facts from authentic sources we must not come to any conclusion and start committing on the issue on various social media platforms. I suggest those people who put allegations and assertions against our reputed medical institutions and doctors to be cautious. I salute my fellow doctors, paramedics, nursing staff, sanitation staff and others who are risking not only their lives but of their families too to make sure people live a better life