16 September 2020
So you think you’ve had COVID-19?
Since arriving back in Australia aboard a COVID-19-laden flight from the United Kingdom in late March, there have been several moments when I was convinced we had picked up COVID-19 on the way.
During the two weeks we remained in strict quarantine at home, my sense of taste and smell were altered and I experienced a persistent headache. For months afterwards, my family and I had very mild stuffy noses, and I suffered with a deep weariness that felt like it went beyond the usual work-induced exhaustion.
But we had no fever, cough or extremes of fatigue beyond what might be expected after a nerve-racking 36-hour international dash home. After we came out of quarantine, I tried to get an RT-PCR test at a local COVID-19 clinic, but was turned away because my symptoms weren’t obvious enough.
But the recent emergence of chilblains – which has been suggested as a possible longer-term side effect of COVID-19 – was enough to push me to get tested for COVID-19 antibodies.
As many as eight out of ten people infected with SARS-CoV-2 may be asymptomatic, which means a significant proportion of the population will have already survived the disease without even knowing it. How do you find out if you’re one of those people?
While reverse-transcriptase polymerase chain reaction testing – RT-PCR – is the current gold standard for diagnosing COVID-19 infection by detecting fragments of SARS-CoV-2 RNA, it only works while the virus is still present in the body. After a matter of weeks, or perhaps a month or two, the virus is cleared and the RT-PCR test will be negative.
This is where serological antibody tests come in. These look for the immune signatures of infection that indicate someone has, at some stage in the past, encountered and survived SARS-CoV-2.
However, testing for SARS-CoV-2 antibodies is much more complicated than testing for viral RNA. The immune system produces a range of different antibodies in response to SARS-CoV-2 infection, these different antibodies appear and peak at different times, and researchers are still working to understand what role each antibody plays in the recovery from and immunity to COVID-19.
“With serology testing, what you see isn’t always what you get,” says Dr Suellen Nicholson, head of the Infectious Disease Serology Laboratory at the Doherty Institute in Melbourne. “PCR is a bit more exact, whereas with serology you can get a lot of interference with antibodies from other viruses.”
Health agencies around the world are currently grappling with the challenge of how to incorporate serological testing into their COVID-19 response and recovery. The United Kingdom has been conducting a population-based serosurvey since late April, with the aim of doing serological tests on a representative sample of up to 300,000 individuals around the country. Already the results of that survey suggest around 6% of the population has had COVID-19.
In the United States, serological antibody tests are available but the Centers for Disease Control advises using them only for people who have a high likelihood of having had the disease, such as a history of symptoms or exposure to infected people.
Australia is also running a series of serosurveys around the nation, testing residual blood samples collected for non-COVID-19 reasons, in an effort to understand exactly how many people have actually been infected with SARS-CoV-2 during this pandemic.
But individuals can also request a COVID-19 serology test from their GP, according to the federal Health Department, and it is currently covered by Medicare. “Access to a serology test is at the discretion of a referring medical practitioner who will make a clinical assessment as to whether a serology test for COVID-19 is appropriate,” a spokesperson for the department told The Medical Republic. There is no specific Medicare item number for COVID-19, they added, but there are existing serology item numbers that can be used.
Not much call for it round here
There was some confusion when I presented to my local GP and asked for a COVID-19 serology test. There isn’t clear guidance online for GPs about the Medicare status COVID-19 serology, but a call to the local pathology service clarified that I could get tested under Medicare.
Dr Jenny Robson, from the Royal College of Pathologists of Australasia warned that because of the low prevalence of COVID-19 in Australia – currently estimated to be less than 0.1% – there’s a high likelihood of false positives with serology tests.
Dr Robson says there are several situations where COVID-19 serology was indicated, including: when a patient has had symptoms consistent with infection but was either PCR-negative or had not had a RT-PCR test; to assess antibody levels for possible plasma donation by patients who have recovered from COVID-19; for contact tracing as part of an outbreak investigation; or in research contexts such as seroepidemiological studies and surveillance of frontline healthcare workers.
There are currently three levels of antibody tests, Dr Nicholson says. The first are screening tests, which look for IgA and IgG antibodies. IgA is the antibody that’s produced in respiratory tract secretions, and is thought to have some neutralising capacity against SARS-CoV-2.
“Because this virus infects your throat and respiratory tract, it’s the IgA that’s produced in that area, that’s what helps protect you against the virus getting into your blood and system that way,” she says. It’s one of the first antibodies to appear, but it’s also fairly short-lived, lasting around three to four months.
IgG antibodies, which are produced by immune B cells, also appear fairly soon after seroconversion.
The next level of serological testing is a more comprehensive total antibody survey that looks for a broader range of antibodies. Then finally, some laboratories – such as the Doherty Institute – perform a microneutralisation test in which a patient’s blood sample is challenged with live virus to see if the antibodies in the patient’s blood are able to bind to the virus and prevent it from infecting cells.
What does it mean?
But does a positive serological result mean a patient is immune? The short answer is no. The slightly longer answer is, “we don’t know”.
“We can’t always be sure with all of the tests, those basic screening tests that we do, that it is neutralising antibodies,” Nicholson says. “Just because you have an antibody-positive result, it doesn’t mean that you’re going to be protected.”
The first confirmed case of reinfection with COVID-19 suggests that infection is no guarantee of protection, and researchers around the world are scrambling to understand the full immunological picture of COVID-19 infection.
“While there is likely to be a reasonable correlation between binding antibodies detected by immunoassays with protective neutralising antibodies, this has not been conclusively proven,” says Robson. “Even if protection is conferred, its durability is unknown.”
My results came back negative, much to my disappointment. Even though I know a positive result doesn’t guarantee future protection, it would have been nice to think I’d dodged the COVID-19 bullet without much more than a snotty nose and sore toes.