Accurate Education – COVID-19 Testing

COVID-19 (COrona VIrus Disease 2019) refers to the infection by the corona virus named SARS-CoV-2 which stands for “Severe Acute Respiratory Syndrome COrona Virus-2,” with the original SARS coronavirus (SARS-CoV-1) identified in 2003 related to another outbreak first identified in China. 

 

What tests are available for SARS-CoV-2?

COVID testing is now available and includes a panel of 3 tests:

 

1. RT-qPCR test – Detects the presence of SARS-CoV-2 virus
   
2. IgM serology test – Detects the early antibody response
3. IgG serology test – Detects the mature antibody response

“Nucleic acid amplification tests,” or “NAAT”

The NAAT test is directed at identifying the presence of the ARS-CoV-2  virus. “Nucleic acid amplification tests,” or “NAAT” tests are molecular tests that detect the virus’s genetic material in a sample that typically comes from a patient’s respiratory system such as anasal or oral swab. FDA-authorized NAAT tests for SARS-CoV-2 meet the EUA statutory standard, and based on the current available data, the FDA believes they are highly accurate. This means that a positive or a negative result from a NAAT test is likely to be true.

 

 

Serology or Antibody Tests

In response to an infection, such as SARS-CoV-2, the body develops an overall immune response to fight the infection. One component of the immune system’s response is development of antibodies that attach to the virus and help eliminate it. A serology, or antibody test, measures the amount of antibodies present in the blood when the body is responds to a specific infection, like COVID-19. This means the test detects the body’s immune response to the infection caused by the virus rather than detecting the virus itself. Serological tests are recommended to be used on patients at least 3 days after onset of symptoms or 7-10 days after infection. The serology test sample is obtained by drawing blood.

   

IgM Antibody

 The body’s initial immune reaction produces general antibodies that attack many infections, called “IgM” antibodies. IgM antibodies appear early and are mostly positive after 3-5 days of onset. A positive result for “IgM” antibodies is likely to indicate that someone currently is in the early phase of infection or has recently had the virus.

 

SARS-CoV-2 IgM antibodies then decrease while the SARS-CoV-2 IgG antibodies increase. During the recovery phase, the titer of the SARS-CoV-2 IgG antibody may increase four times or more compared to the acute phase.

   

Because it takes time for the body to make IgM antibodies in response to SARS-CoV-2, their absence does not mean that someone is not infected, particularly in those who have recently been in contact with the virus. A test for IgM antibodies may give a false negative result in a patient with SARS-CoV-2, particularly early in infection, even when they are symptomatic or asymptomatic but actively shedding the virus. Since IgM antibodies may not develop early or at all in infected patients, this type of antibody test is not used solely to rule out SARS-CoV-2 in an individual.

IgG Antibody

Over time, the body develops a second type of antibody in response to the infection that is more specific to the virus, called “IgG” antibodies. Most antibody tests detect IgG antibodies. On average, IgG antibodies take about 4 weeks to develop, but the time to development may vary substantially, and there is still a lot we do not know about SARS-COV-2. Since IgG antibodies generally do not develop until several weeks after infection, this type of antibody test, even though it is more specific to SARS-CoV-2, is not used solely to rule-out SARS-CoV-2 infection in an individual.

 

False Negative Testing

As noted above, in the early days of an infection when the body’s immune response is still building, antibodies may not be detected, leading to a negative test result falsely indicating absence of disease. This limits the antibody test’s effectiveness for diagnosing COVID-19 and why it should not be used as the sole basis to diagnose COVID-19.

 

False Positive Testing

Positive results may also be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E. None of these viruses are currently known to be causing active disease in this area at this time.

 

Interpretation of the 3 tests:

Does the presence of IgM/IgG antibodies mean one is immune to re-infection of SARS-CoV-2?

This is the million dollar question for which there, again, is no definitive answer. In general, the presence of significant levels of IgG antibodies confers relative immunity to the illness in question. By relative, again in general, it is meant that immunity is likely good for an indeterminate time but the strength of that immunity may fade over time which is why some vaccinations must be repeated every 5 or 10 years – for example, with tetanus vaccines.

 

In the case of SARS-CoV-2, there have been no studies that specifically confirm immunity against reinfection and some, including the World Health Organization, argue therefore that positive IgG testing should not be relied upon as confirming immunity. Which is likely good advice since there are few absolute certainties in this world. But the question then becomes, why shouldn’t it? To answer this, one needs to understand the basics of the immune response to illness such as SARS-CoV-2.

What we do not know

1. We do not know how long an asymptomatic patient testing positive for RT-qPCR remains contagious.
2. We do not know how long IgM or IgG antibodies to SARS-CoV-2 will remain present in the body after the infection has been cleared.
3. We also do not know whether or not the presence of IgM and/or IgG antibodies confirms immunity to re-infection. Nor is it known how long a person who has recovered from the virus may be at lower risk of infection if they are exposed to the virus again.
4. With the other four coronaviruses currently endemic in humans, we know that immunity disappears gradually over time — it likely takes years but we don’t really know. Adults might get infected with the same virus they had as a child, but even if someone gets sick with the coronavirus again, the second infection might not be as bad.