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As the COVID-19 pandemic spreads, the scientific community is working in overdrive to deliver faster and cheaper diagnostic tests. The need of the hour is to have tests that are easy to administer, accurate and easily accessible.

The diagnostic tests for SARS-CoV-2 are broadly divided into two categories, Molecular Tests and Serological Tests.

1. Molecular Tests for SARS-CoV-2

These tests detect the presence of SARS-CoV-2 genome (RNA).The different techniques for performing molecular tests for SARS-CoV-2 are as under:

• The most common technique is the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).This test is used to confirm very recent or active infections. The sample for this test is mostly taken from deep nasopharyngeal swabs.
• Isothermal Nucleic Amplification is another molecular testing technique that detects the viral RNA. It is much faster than RT-PCR and gives positive results in five minutes and negative results in under fifteen minutes. On March 18th US FDA (Food and Drug Administration) approved a test by Abbot Laboratories that uses this technique. The machine that performs the test is the size of a toaster, so it is convenient to move around and the test is easy to perform.

The deep nasopharyngeal swab collection for molecular tests is done by the healthcare professionals, standing in close proximity to the patient, thereby exposing them to exhaled droplets. This necessitates the use of Personal Protective Equipment (PPE), which could otherwise be used for patient care. The actual procedure of taking the swab is uncomfortable for patients and difficult to perform in young children and infants. There is also an ongoing shortage of these kits, besides which, the method of collection is more time consuming. Other types of samples for doing the molecular tests have been explored and found to be sensitive and specific for detection of SARS-CoV-2. These samples are collected by self, so health care professionals are spared for other important roles.

The newer types of samples for performing molecular tests are:

• Saliva based diagnostic tests for SARS-CoV-2: Traces of SARS-CoV-2 were detected in the saliva of 11 out of 12 hospitalized COVID-19 patients, as reported in a study published in Clinical Infectious Diseases. Presence of the viral genome in the saliva could mean that the virus possibly infects the salivary glands. However, the salivary specimens contain not only saliva secreted from the major and minor salivary glands, but also secretions coming down from the nasopharynx and secretions coming up from the lower respiratory tract via the actions of cilia lining the airways. Hong Kong started the saliva based testing in early March. In early April US, FDA gave its first emergency authorization for saliva based testing for COVID-19. The patient spits into the collection device and puts the cap on. This releases the preservative solution into the vial. The outside of the vial is wiped with an alcohol pad and the collection kit is handed over to the health care professional. The results are available after 24-48 hours.

• Stool Testing for SARS-CoV-2: False negative deep throat saliva test increases to over 40% with improper collection technique, more so in case of children and infants. It is now well known that the virus can also be detected in stools. In fact, it can persist in stools after clearance from respiratory tract. Stool Test for SARS-CoV-2 is highly sensitive and specific. In Hong Kong it is being used as a noninvasive screening test for asymptomatic population such as young children and infants. Stool Collection kits are given to the travelers entering Hong Kong. They collect their stool samples and return the collection kit to centers designated for deep throat saliva collection.

2. Serological Tests for SARS-CoV-2

These tests detect the body’s immune response to SARS-CoV-2 rather than the virus itself. The body produces antibodies in response to the viral infection, first the IgM and later IgG antibodies. The antibodies (Immunoglobulins) are detectable in blood samples several days after the initial infection. This limits the effectiveness of these tests for diagnosing early infection. The serological tests can be used to determine those people who have developed antibodies to the virus and are therefore, probably immune to the infection. In addition, these test results can aid in determining which patients can donate their convalescent plasma, for possible treatment of critically ill COVID-19 patients.

Serological tests are an invaluable tool in detecting community spread of SARS-CoV-2. A number of studies amply illustrate this use of serological tests. A study form Gangelt, Germany, reported on April 10, 2020, that 15% of the people tested positive for anti SARS-CoV-2 antibodies in a study population of thousand people form that area.

Two research teams in California, one from Stanford University and the other from Boston Children’s Hospital conducted Serological tests on 3,300 volunteers in the Santa Clara County. The preliminary results were announced on April 17, 2020. It was found that 2.5% to 4.5% of the volunteers were positive for antibodies against SARS-CoV-2. This means that, of the two million population of Santa Clara County, between 48,000 to 81,000 people may have had the virus as opposed to the approximately 1000, in the county’s official tally at the time samples were taken.

A study conducted by Massachusetts General Hospital, on 200 volunteers from Chelsea, revealed on April 19, 2020, that 32% of those tested, had antiviral antibodies. This is in stark contrast to the official positive rate of 2%.

The serological tests have been quite revealing as regards the true extent of the infection in the community. It is uncertain whether this data can be extrapolated to the rest of the country where the studies were conducted.

Conclusion

It is quite clear that detecting viral RNA by the molecular tests is the gold standard for diagnosing early SARS-CoV-2 infection. Newer and faster types of test kits and newer types of samples for testing, will make it possible for more and more people to be tested. This will not only assess the true incidence of the disease but will also help healthcare professionals to take protective measures to prevent spread of COVID-19 from the newly diagnosed, symptomatic and asymptomatic cases. The serological tests on the other hand, will help the scientific community in assessing the true prevalence of the disease.