Understanding the Coronavirus (COVID-19) Testing and Immunity

MedMaven

by Dr. C.H. Weaver M.D. 9/2020

As citizens seek security and protection from the COVID-19 pandemic the media has fostered the narrative that governments around the world have failed to appropriately respond to the pandemic by not having accurate testing in place. While accurate testing data is helpful to best manage this pandemic, a concern is that the media has perpetuated a false narrative on the ability of current testing techniques to provide actionable useful information. Testing has improved significantly since the beginning of the pandemic and can now reliably diagnose an active COVID-19 infection and provide some insight into whether an individual develops immunity to COVID. Recent reports of individuals becoming infected with COVID for a second time however raise concerns about the strength and duration of immunity in some individuals.

So How Do Medical Tests Work?

Any medical test has two important qualities: sensitivity and specificity. In the case of the Coronavirus tests are proven to be “sensitive” by detecting the smallest amount of virus. The tests must also be “specific” ensuring they do not mistake other pathogens, such as influenza or rhinovirus for the new SARS-CoV-2. When developing a test, researchers typically make some trade-offs between sensitivity and specificity – in other words it’s almost impossible to be 100% sensitive and specific.

First and foremost it’s important to understand that no test evaluating the COVID-19 virus will be 100% accurate. Some test results incorrectly determine that a person is infected when they are not – these are called “false positive” tests. Some tests determine that someone doesn’t have the virus infection, but they do. These are called “false negative” test results. While false positive tests are disconcerting to the individual, it’s the false negative results for COVID-19 that are the main problem for managing the pandemic.

IgM-IgG Antibodies Against COVID-19

Identifying antibodies to the coronavirus (SARS-CoV-2) in an individuals bloodstream can be used to determine whether a person previously had COVID-19. The test is most useful for policy makers and scientists for tracking the pandemic. This test cannot determine if you have an active infection, determine if you are infectious to other people, or confirm immunity to re-infection with certainty. Having this test does not change recommendations for social distancing, hand washing, no-face-touches, surface disinfection, etc.

Your bodies immune system makes IgG and IgM antibodies that can be detected it the blood and provide useful information about an individuals past exposure to the virus but not much is known about immunity. This is not a test to detect active infections, it looks for antibodies after an individual has had an infection. In fact the sensitivity of antibody testing is poor until at least 3-4 weeks after the initial infection. A positive result means that one has been exposed to and has developed an immune response to the SARS-CoV-2 virus. Both IgM and IgG antibodies are created gradually over the course of 1-2 months

  • IgM stays positive for ~ 6 months or longer.
  • IgG is usually associated with immunity and could stay positive for 2 years or longer (based on old SARS-CoV-1 coronavirus studies)

Does IgG or IgM Predict Immunity?

Although serological assays to detect SARS-CoV-2 IgG and IgM antibodies are available it is presently premature to use such assays to determine whether individuals are immune to reinfection.

Understanding whether and how recovery from a COVID-19 infection confers immunity to or decreases the severity of reinfection is needed to inform current efforts to safely scale back population-based interventions, such as physical distancing. Following infection with COVID-19, detectable IgM and IgG antibodies develop within days to weeks of symptom onset in most infected individuals. It remains to be determined however whether a robust IgG response corresponds with immunity. Well-designed longitudinal studies of persons who recovered from COVID-19 are needed to monitor for signs and symptoms of recurrent illness.

The potential for cross-reactivity with other coronaviruses (yielding false-positives) have yet to be determined. Widespread testing of persons who have not had COVID-19, a population with low SARS-CoV-2 prevalence, can generate more false-positives than true-positives. We do currently know however that

  • Two cases of SARS-CoV-2 reinfection have now been confirmed.
  • There is also no evidence that individuals infected with SARS-CoV-2 have transmitted the virus to others after they had clinically recovered. However, this possibility of transmission cannot be ruled out.

World's First Confirmed Cases of COVID-19 Reinfection Reported

A reportedly young and healthy patient was documented to be infected with COVID-19 4.5 months after the first infection according to doctors at the University of Hong Kong. The patient is a 33-year-old man in Hong Kong who had mild symptoms the first time he was infected, and no symptoms the second time. The researchers said his reinfection was discovered after he returned from a trip to Spain, and the strain he had closely matched one circulating in Europe in July and August.

Several cases of suspected reinfection have been seen in the United States and elsewhere, but until this week none were confirmed. A second man in Nevada has also been reported to have been infected with COVID-19 for a second time. Evidence of reinfection is a cause for concern because it suggests that immunity to the new coronavirus may last only a few months in some people.

It’s important to understand however that there is a “spectrum of immunity” that ranges from complete immunity to very short durations of immunity. Once someone recovers from a novel coronavirus infection, are immune from the virus at some level but the strength of the immunity and its duration are unclear. The two recently reported cases from Hong Kong and Nevada suggest that immunity is not absolute, and people previously thought to be immune can get a second COVID-19 infection.

Individuals exposed to the virus do have an increase in their antibody levels however the strength of their immunity appears to be related to the severity of their initial infection. People who have a mild or asymptomatic infections may have a lower immunity level as evidenced by lower levels of antibodies that can be detected.

In summary, existing limited data on antibody responses to SARS-CoV-2 and related coronaviruses, as well as one small animal model study, suggest that recovery from COVID-19 might confer immunity against reinfection, at least temporarily. However, the immune response to COVID-19 is not yet fully understood and definitive data on post infection immunity are lacking. (1)

Like other serological, or antibody-based, diagnostic assays, it uses an enzyme-linked immunosorbent assay (ELISA), which employs a portion of the target virus to find antibodies. Although serological tests are not useful for quickly identifying whether a patient currently has COVID-19 the help researchers understand how humans produce antibodies to the virus. Serological tests can also help determine if a person has been infected whether or not the individual had symptoms—something an RNA test kit cannot do after the fact, because it only looks for the virus itself. That means serological tests could be used to survey a population to determine how widespread infection rates.

How Do Doctors Test for COVID-19 Infection?

Until August 2020 the main way people were tested for COVID-19 was to place a sterile swab at the back of a patient’s nasal passage, where it connects to the throat via the nasopharynx, for several seconds to absorb secretions. After a sample is collected, the swab goes into a liquid-filled tube for transport.

To determine whether a nasopharyngeal sample is positive for the coronavirus, biotechnicians use a technique known as reverse transcriptase polymerase chain reaction, or RT-PCR. To perform this test a technician extracts viral genetic material called RNA (if it is present) from the sample and uses it to produce a complimentary strand of DNA that the RT-PCR technique amplifies, or makes thousands of copies of, to get a measurable result. The primary difference from one kit to another is which coronavirus genes each test targets.

FDA Approves Saliva Test for COVID-19

The FDA issued an emergency use authorization for the SalivaDirect COVID-19 diagnostic test that allows for saliva samples to be collected in any sterile container, rather than a nasal swab.

Interpreting Test Results

When the test is positive it provides “actionable” information. If you have a positive test we consider a person infected and potentially contagious. A negative test is harder to interpret.

It is essential to understand that a negative test does not rule out COVID-19 infection. It is currently estimated that the COVID-19 test is falsely negative 15% to 50% of the time. When diagnostic testing is negative, the possibility of a false negative result must be considered in the context of a patient’s recent exposures and the presence of clinical signs and symptoms consistent with COVID-19.

There are a number of reasons a test might be negative when a person is sick with the coronavirus.

  • It might be too early in the illness, when the amount of virus in the airway is still small.
  • It could be a problem with how the swab was done.
  • Swab collection techniques; the back of the nose, the throat, the outer nose have different levels of accuracy.
  • Issues with the handling or transport of the swab. There could be laboratory error.
  • The test is also only true for a single point in time. A person who sought testing for symptoms caused by another pathogen could easily contract the coronavirus in the time between being swabbed and receiving the result. Or if they are early in the illness, they might test negative because the virus hadn’t multiplied enough.

Some Who Tested Negative Have Tested Positive Again

There is currently an increase in “second-time” infections in Wuhan, further calling into question the accuracy of COVID-19 diagnostic testing as China prepares to lift quarantine measures that would allow residents to leave the city. It's also raising concerns of a possible second wave of cases which in the case of the 1918 pandemic proved to more fatal than the first wave.

From March 18-22, the Chinese city of Wuhan reported no new cases of the virus through domestic transmission, but some Wuhan residents who had tested positive earlier and then recovered from the disease are testing positive for the virus a second time. It has been reported that as many as 15% of individuals testing negative on two occasions subsequently tested positive again 2-3 weeks later.

It is unknown if those who retested positive are asymptomatic carriers or are infected again. Asymptomatic carriers are infectious but do not exhibit any of the illness's associated symptoms. On the other hand, could a second positive test mean a second round of infection? Most experts believe it is unlikely that a COVID-19 patient could be re-infected so quickly after recovery, but it is too soon to know for certain.

Other Testing Techniques

Novel Rapid Tests: Abbott labs is releasing their recently approved coronavirus test that is reported to be able to tell if someone is infected with COVID-19 in as little as five minutes. The new Abbott ID NOW COVID-19 test runs on Abbott's ID NOWTM platform which is a small ~ 6 pound box that can sit in a variety of locations allowing testing to be quickly performed at the point of care. Similar tests will be released by other companies as well.

The test still relies on correctly taking a swab from the nose or the back of the throat, then mixing it with a chemical solution that breaks open the virus and releases its RNA which is then amplified and measured by the device. The test will be helpful for more rapidly identifying infected individuals based on a positive test. This is especially useful for health care workers and first responders who test positive, so they don't place others at risk. Given that the sample obtained for test is identical to that used for currently available tests the false negative rate is unlikely to be any better than the other available tests so negative test results carry the same problem of not providing a high level of certainty that one is not infected. It also could allow public health agencies to figure out who is already immune to COVID-19

Lastly, remember that over testing drains sorely needed personal protective equipment that health care providers need to perform their vital functions during the pandemic. Testing should not be routinely performed on all individuals and reserved for those with symptoms consistent with an active infection.

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References:

  1. doi:10.1001/jama.2020.7869
  2. FDA press release, August 17, 2020; STAT, August 17, 2020; Vogels, CBF, Brackney D, Wang J, et al. SalivaDirect: Simple and sensitive molecular diagnostic test for SARS-CoV-2 surveillance. medRxiv preprint. August 4, 2020.
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