Why we still can’t test for Covid-19 immunity

There are more than 600 antibody tests on the European market but they have little value if we don't know what kind of immunity response is needed to protect against Covid-19 reinfection or breakthrough infection. Keystone / Ciro Fusco

Many countries are betting that the pandemic’s end is in sight, but public health experts are more cautious. One reason is that we still don’t have a test that tells us about our immunity to the virus.

Shortly after the first reported coronavirus case in Switzerland on February 25, 2020, technology firms and medical researchers began mulling the idea of digital certificates that prove immunity to the Sars-Cov-2 virus. The idea was quickly muted as it became clear that there wasn’t enough information about what type and level of antibodies would meet the threshold for immunity.

While Switzerland, like many countries, eventually developed a Covid certificate that captured a person’s vaccination or infection status, public health officials have been cautious about equating the certificate with something akin to an immunity pass.

Two years into the pandemic, the ability to measure immunity is still a work-in-progress, says Didier Trono, who heads the virology and genetics lab at the Federal Institute of Technology in Lausanne (EPFL).

“I wouldn’t say we are navigating without radar, but we are still at an early stage of understanding everything,” Trono, who chaired the diagnostics expert group of the Swiss National Covid-19 Science Taskforce, tells SWI swissinfo.ch. “We still don’t know, statistically speaking, antibody levels that tell us if someone is resistant to infection, can pass on the infection to others, and whether they are protected against the disease.”

Public health experts and politicians in Switzerland agree that monitoringExternal link the immunity level of the population is key to keeping the virus at bay especially as most pandemic restrictions have now been lifted. But they still don’t have the tools to do so.

Missing link between antibodies and immunity

There are currently 632 antibody tests and supplies authorised for sale on the European marketExternal link. Most of these tests detect and measure antibodies in the blood, which are protective proteins produced by the immune system when it spots a foreign substance such as a virus.

These types of tests have been used in serological studies in Switzerland that capture the share of the population exposed to the virus.

But such tests have little use at a time when almost everyone in the population has had Covid-19 or been vaccinated. In June 2021, one such studyExternal link in canton Fribourg found that 73% of people over 20 years old had Covid-19 antibodies.

“Something that measures antibodies against the virus without specifying how many or how they bind to the virus is worthless. Once you’ve been infected or vaccinated, you’re very likely to keep some trace of the virus antibodies in your body for years,” says Trono.

Even as recently as last November, Virginie Masserey, who heads the infectious diseases department at the Swiss Department of Public Health, warned the public at a press conference that “positivity on antibody tests is only an indication of infection and says nothing about protection”. At the time, pharmacies in Switzerland were inundated with customers wanting to test their antibody levels, while some boutique hotels and wellness centres in Switzerland and elsewhere offered such tests as part of an “immunity check-upExternal link”.

Didier Trono leads the virology and genetics lab at the Federal Institute of Technology in Lausanne (EPFL) and chaired the diagnostics expert group of the Swiss National Covid-19 Science Taskforce. He received his medical degree in Geneva and did his clinical training in pathology, internal medicine and infectious diseases in Geneva and at Massachusetts General Hospital in Boston. Keystone / Jean-christophe Bott

Omicron only reinforced scientists’ fears that antibody tests gave a false sense of security. Since Omicron appeared, many more people are getting Covid twiceExternal link. One statistic from the United Kingdom showed reinfection was 16 times higherExternal link since Omicron.

Perhaps more concerning though is immunity after an Omicron infection. Trono’s lab along with colleagues in Geneva have unpublished data showing post-Omicron immunity is weak. People who have been infected with Omicron but not previously vaccinated or infected with another variant reveal that their blood hold levels of what are called “neutralising antibodies”, are low to almost non-existent. These are the antibodies that are most important for understanding immunity because they bind to the virus and prevent it from entering into its target cells.

“It’s too early to see many people getting Omicron twice but the concern is for the future, irrespective of variants, notably for people that only have been infected by omicron but not vaccinated or infected by other variants,” says Trono.

Immunity levels also seem to vary depending on whether someone has mild or more severe symptoms, the timing of infection and vaccination, and other health factors. While none of this is surprising, it is confounding efforts to develop tests that assess immunity.

Studies are starting to fill some of the blackboxes on immunity though. One studyExternal link, published in December 2021, showed significantly more neutralising antibodies after three vaccination doses than two. Another studyExternal link by Stanford University revealed differences in both levels and specific structure of neutralising antibodies in people who had a mild versus a severe course of the disease. The study authors said this could help create a test, that if given right after a Covid-19 infection, could determine likelihood of hospitalisation.

ResearchersExternal link are also looking at the T-cell response to the virus, which is another important element of immunity. T-cells kick-in after the virus enters the cells making them a second line of defense after antibodies. Some expertsExternal link even argue that any protection after Omicron infection is more likely from T-cells than antibodies.

Precise and personal tests

As more studies like these emerge, scientists and diagnostic makers are refining their suite of tools to provide a more nuanced picture of immunity.

Trono’s team at EPFL in partnership with the Lausanne University Hospital (CHUV) developed a blood testExternal link in July 2021 that measures the amount of specific neutralising antibodies. In contrast to other such tests, it isn’t virus- and cell-based, which are typically expensive and time-consuming. His team is now correlating results with data on reinfections and breakthrough infections, which they hope to share in a few weeks. They are meanwhile looking for ways to commercialise the test.

The Paul Scherrer Institut, which is the largest research institute for natural and engineering sciences in Switzerland, has developed a rapid testExternal link using a blood sample and fluorescent nanoparticles to measure both short term and long-term antibodies, that could indicate the course of the disease. It can also be used to identify a variety of pathogens, such as those responsible for the flu. 

Swiss pharmaceutical firm Roche, which is one of the biggest makers of Covid-19 tests has also been working to correlate protection or risk of Covid-19 with results from its antibody testsExternal link. In a written statement the company told SWI, that it had initiated several studies with partners in the last few months to create “a database that could allow us to define a protective correlate”, which is the level of immune response needed to protect against Covid-19 in the future.

One of those partners is Moderna. The US vaccine maker has been using Roche’s antibody tests in vaccine trials since December 2020. Thomas Schinecker, CEO of Roche, said at a press conferenceExternal link in mid-February that the company will be launching a new antibody test as well as a T-cell test this year. The hope is that these insights could help determine when an individual requires an additional “booster” vaccination dose.

The real test, says Trono, will be when these different tests are validated in large samples of the population and people are followed to see if they get reinfected. “Once we see breakthrough infections or reinfections and can correlate that to some kind of number obtained in these tests, then we will be able to say they are reliable and a good surrogate of protection,” says Trono. “Until then, I would be careful about making any claims of immunity.”

Edited by Sabrina Weiss