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Diagnostic Testing for Coronavirus

April 21, 2020

COVID-19 Testing

Coronavirus is part of a common virus family that causes upper respiratory infections. These viruses are ubiquitous, primarily targeting the respiratory system, leading to symptoms of fever, cough, nasal congestion, shortness of breath, body aches similar to that of other common colds or flus and are generally self-limited. The novel Coronavirus of 2019, designated SARS-COV-2, belongs to this family of viruses, appears to have greater transmissibility and causes more symptom severity and mortality than its common cousins resulting in a specific Coronavirus disease termed COVID-19.

Due to the novelty, much about the virus is still unknown and it has resulted in unprecedented socio-economic disruption. As with any disease, diagnostic testing is part of discovery to better understand the epidemiological characteristics of the infection. Once identified, clinical regimen and public health initiatives can then be implemented to better manage the course of the contagion. In this article, we explore the different types of diagnostic testing commonly available, and discuss the applications and limitations of each.

The two primary tests are the human Antibody Test and Viral Genetic PCR testing. Every medical test has its specification and the corresponding results provide certain conclusions. It is important to delineate the differences of the tests in order to truly understand the relevance of the results. One important point to highlight is that no test is 100% accurate. This is not unique to COVID-19 testing and applies to all medical tests; therefore, when discussing any diagnostic, it is important to understand what it measures, and how often false positives or false negatives occur.

Antibody Test
The most common test is the Anti-body test. Antibodies are produced by the body as a defense mechanism when it is exposed to an offending microbe. The specific type, onset, scale, and duration of antibody response varies by type of exposure and is also unique based on an individual’s genetic makeup. Different types of antibodies are produced, but the relevant ones in the case of COVID-19 are IgM and IgG. IgM antibodies are produced first, and IgG antibodies last longer. Antibodies, when present, generally confer some type of immunity or protection against future reinfection from the same agent. Antibodies are also specific, so if the exposure is dissimilar, then its utility may be limited. This is the case with influenza which varies from year to year, blunting the immunity response. Finally, antibodies have memory, some lasting for almost a lifetime in the case against measles, while others not.

The COVID-19 antibody analysis identifies prior exposure or active infection with SARS-CoV-2 and identifies potential immunity. Production of antibodies for this specific virus strain takes about 8-10 days post-exposure. During this time a person may test negative and still be contagious with the virus. Currently all antibody tests require administration by a healthcare professional. Testing involves obtaining a blood sample at the point of care. Antibodies tests are economical, and useful for large scale screening from exposure. Analysis is limited in early infection before antibody production or cases of weak immune response, which can result in false negative tests during which an individual may harbor the virus and be contagious.

PCR Test
The clinical gold standard test for detecting the presence of SAR-COV-2 is a viral genetic PCR test. Viruses like other microbes contain genetic material in the form of DNA or a related compound called RNA which serve as a blueprint for the virus to copy itself. PCR, short for polymerase chain reaction, is a technical method which multiplies the amount of genetic material obtained in a sample so that it can be detected by the measuring instrument. This sensitive technique allows for even a just few virus particles to be identified.

PCR testing involves obtaining a sample usually via a nose or oral swab. Since Coronavirus primarily affects the respiratory tract, it is concentrated in saliva and nasal secretions. Once collected, the sample is placed into a fluid medium that preserves the genetic integrity of the virus. The sample then needs to be measured by an instrument which identifies the specified virus material.

This modality requires sophisticated lab equipment, and in most cases takes some time to provide results (one to few days). The test is more cost prohibitive but detection accuracy is very high. Negative tests effectively rule out the presence of the virus. A positive test signifies transmissibility but may occasionally detect inactive viral particles. This analysis offers a snapshot or a picture of an individual’s present state but does not provide information about prior exposure or presence of antibodies.
During the course of an infection, a person first contracts the virus. Then the body mounts an immunological response which usually ends in the elimination of the virus. The PCR test is focused on virus detection and the antibody test looks at exposure and the body’s response. Due to the novelty of SARS-COV-2, there is limited long term data. SARS is a disease caused by a different strain of Coronavirus and responsible for the epidemic in 2003. The virus is related to the current contagion and data suggests that antibodies against SARS were present for about 2 years (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/), having an important role in protective immunity during that timeframe. As previously noted, due to the novelty of the current virus that data is not available and active research is ongoing to help clarify the conundrum.

In summary, antibody and PCR tests work differently. One is not superior to the other. When utilized in tandem and sequentially, the tests provide a multitude of information that allow clinicians and researchers to make recommendations on important matters such as social isolation and return to work. This is of crucial importance both to the individual and for public health during this unprecedented crisis. It is everyone’s responsibility to get tested to help further understanding of COVID-19 and the first step of responsible action in the return to normalcy.

Combination Testing Profiles

Combination Test Result Interpretation Future Actions
+ Antibody, (-) PCR Possible immunity with no active infection May return to work with subsequent testing to determine duration of possible immunity. Ancillary services for immunity and Virus activity.
+ Antibody, + PCR Remote exposure to Virus with active infection Isolation and observation of recovery. Repeat testing can provide quantitative data on return recommendations. Genetic testing to identify correlation with symptoms. Considerations on repeat infections. Ancillary services for immunity and Virus activity.
(-) Antibody, + PCR Recent exposure to Virus with active infection Isolation and observation of recovery. Repeat testing can provide quantitative data on return recommendations. Ancillary services for immunity and Virus activity. Epidemiological trace studies to identify others at risk.
(-) Antibody, (-) PCR No exposure to Virus, no active infection. Repeat serial testing and DNA analysis. Universal precautions. Ancillary services for possible immunity and Virus activity. Urgent immunization when available.

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