A tiny organism, only the size of nanometers, has disrupted the flow of ordinary life. This organism is a virus, called SARS-CoV-2, and it is the driving force behind the COVID-19 outbreak. Though undetectable to the naked eye, researchers around the world are stressing the importance of identifying hosts of the lethal virus. Widespread testing could help identify and isolate patients, helping to flatten the curve of COVID-19 infection. Currently, there is only one method of testing, and it is relatively costly and time consuming. This lack of efficient testing leaves humanity at a serious disadvantage in the arms race against SARS-CoV-2. In an attempt to remediate this issue, this study has suggested using serological testing to help meet testing needs. The study found that serological testing is an effective testing method for SARS-CoV-2 with its fast turn-around, low workload, and ability to predict the severity of symptoms.
As of April 9th, 2020, there were over 1.5 million confirmed cases of COVID-19 worldwide. These cases were confirmed through RNA testing, the only testing method currently available. RNA is the genetic material of viruses, which can be detected in samples of the upper respiratory tract, collected via swabs of the throat or nasopharyngeal tract. The samples are then analysed for the unique genetic markers of SARS-CoV-2. While RNA testing has high accuracy, it has low real-life performance. For one, sample collection and analysis is very sensitive to contamination, and measures to ensure sterility are timely and expensive. As such, testing is often restricted to health care workers, individuals with direct contacts with confirmed patients, and patients with symptoms characteristic of COVID-19. Additionally, RNA testing sensitivity is highest at the beginning of the illness so viral RNA may not be detectable during later stages of infection. Â As a result, RNA-based testing is not a practical option for widespread testing, creating a bottleneck for early detection and monitoring of COVID-19 patients. Â
In pursuit of a serological test for SARS-CoV-2, a research team led by Juanjuan Zhao studied the antibody response in COVID-19 patients. Their hope was to find a consistent antibody response that can be readily and reliably identified using serological testing. Serological testing is an indirect form of testing that detects the immune response in the form of antibodies, instead of the presence of the virus itself. Antibodies initiate a targeted defence against intruders and bind to the proteins on the surface of the virus with lock-and-key precision. These antibodies are formed early after the onset of infection and can be detected in body fluids. To perform a serological test, a blood sample is collected and analysed for the antibodies specific to the virus of interest. The presence of antibodies is assessed using an enzyme-linked immunosorbent assay, also known as ELISA. ELISA uses an antigen that mimics the spike protein found on the surface of the SARS-CoV-2 virus. As such, antibodies can bind to the antigen used in ELISA the same way that they would bind to the virus. Then, an enzyme binds to the antibody-antigen complex and produces a colored reaction so that the presence of antibodies can be detected. This process is illustrated in the figure below.
For Zhao’s study, blood samples were collected from 173 COVID-19 patients to test for Ab, IgM, and IgG antibodies. Ab is to the overall antibody response, while IgM and IgG are specific immunoglobulin antibodies that circulate in the blood. A total of 535 blood samples were collected from patients at different stages of infection and assessed for antibodies using the ELISA method described above. The Ab assay was found to be the most sensitive test and produced a positive result sooner after onset than the assays for IgM and IgG. In 90% of patients, the Ab assay produced a positive result by the 12th day after onset of illness, and 100% of patients had a positive result one month after onset. As a result, serological testing for Ab is effective for detecting SARS-CoV-2 during later stages of illness.
Serological testing is much more efficient than RNA testing as it has a faster turn-around time and high throughput, meaning it has the potential for widespread testing. Widespread testing will help flatten the COVID-19 curve by enforcing quarantine of confirmed patients and allowing for contact tracing of other potential carriers. Unfortunately, access to testing is currently restricted all around the world. Priority for testing is given to health care workers, individuals with close contacts to a positive case, and people with characteristic symptoms of COVID-19. However, it is believed that there could be a large number of asymptomatic carriers at large in our society, contributing greatly to viral spread. Because serological testing is a relatively quick and cheap method of screening for infection, it could be used to identify these carriers and impose quarantine.
Serological testing also has the potential for uses beyond diagnostics. For one, the concentration of Ab in a patient’s blood sample can be used to predict the severity of illness. Zhao and colleagues found that patients who developed a critical condition had experienced a marked increase in Ab concentration approximately 2 weeks after onset. Additionally, serological testing has been suggested as a way to screen employees before they return to work. It is possible that the presence of antibodies in individuals who are no longer ill may be linked to some immunity against the virus. First, further studies are required to better understand the immune response to SARS-CoV-2. If proven to be true, serological testing could a useful tool to revive the economy.
Serological testing, as proposed by Zhao and colleagues, has the potential to significantly increase the number of COVID-19 diagnostic tests administered worldwide. Serological testing is much cheaper, more timely and easier to administer than RNA testing. As such, it is a more practical option for widespread testing of non-priority individuals. Serological testing could also be used in addition to an RNA test to increase confidence of diagnosis or identify false negatives. Furthermore, serological testing could be used to identify high-risk COVID-19 patients, or as a screening mechanism to revitalise the depleted workforce.













