The sheer speed with which Covid-19 spread across the world, coupled with the novel nature of the virus, has meant that scientists and technicians have been playing a game of catch-up. But our knowledge, though incomplete, is now much greater than it was at the start of the outbreak, and medical systems are better equipped to respond.
Part of this means we’ve got better at testing for the disease – attempting to meet the demands of people who want to know if they are, or have been, infected. Dr Alex Richter leads the clinical immunology labs at the University of Birmingham, where I work, and her team has developed serology tests that detect antibodies to Sars-CoV-2.
For the time being, laboratory tests such as theirs are more sensitive than commercial antibody kits. But an increasing number of the latter are becoming available around the world, many of them over the counter.
As we go further down this road, it’s important that people understand what antibodies reveal about our immune response to Covid-19, and how protective immunity works.
Basically, antibodies to Sars-CoV-2 show that you have been infected, although people with other recent coronavirus infections (which includes some common colds) may have cross-reactive antibodies, giving false positives.
Serology tests vary in accuracy, but are more effective than so-called polymerise chain reaction (PCR) tests, which detect the presence of the virus itself. One reason is that they rely less on the skill of the person doing the sampling: antibodies in the blood are easier to detect than virus particles in nose or throat swabs.
Such tests provide useful information about the way an infection has spread through a population. Newly infected people are unlikely to have detectable antibodies during the first few days, but most develop them after one to three weeks. Knowing how many have become infected helps us estimate the percentage of severe cases and deaths more accurately, and this tells us more about just how dangerous the new pathogen might be.
It also helps us identify high-risk groups, which can offer clues as to how the virus may be transmitted. Take Richter’s study, in which she tested 516 healthcare workers for Covid-19 antibodies: 34 percent of housekeeping staff came back positive compared with only 15 percent of staff working in intensive care. Such insights can be used to shield vulnerable groups with protective interventions.
Antibodies also offer hope for future protection – but we have yet to fully characterise what immune protection from Covid-19 might consist of.
There are two major types of “memory” immune responses – changes to the body that mean you are able to recall a previous threat in order to mount a rapid protective response on reinfection. The first is driven by B cells, which produce antibodies. Vaccine research aims to generate potent, long-lasting antibodies that can protect us for life, but this is not always achieved. When antibodies wane, booster vaccinations can help. When viruses evolve to escape detection, like the fast-mutating flu, a newly designed vaccine is needed to stop them in their tracks.
The second cell type able to remember an infection is the T cell. T cells may be sufficient to control infection in the absence of antibodies, and act by organising immune defences (so-called “helper” T cells) or directly killing infected cells to restrict new virus production (cytotoxic T cells). T cell responses have been detected in most Covid-19 patients, and first-in-human vaccine trials have reported potent T cell activation. It is possible that T cells’ memory of Sars-CoV-2 may last longer than antibodies, as is the case in other coronaviruses.
Can you develop a T cell response without developing antibodies? That seems to be a possibility: a small study of patients and their families shows that an unexpected six out of eight family members who caught the virus at home had T cell responses but no detectable antibodies.
Currently there isn’t an off-the-shelf test to measure our T cell responses, and they do not show up in antibody tests. But then even a positive antibody test, at this stage, doesn’t tell us all that much about protection. The duration of any potentially protective immunity remains to be determined. As with so much related to this pandemic, we will know more as the months pass, and people who have recovered either remain well, or succumb to the virus again.
Perhaps of more practical importance right now is a study that followed up 37 asymptomatic people who had positive PCR tests. This showed they had detectable levels of the virus for longer that those who had symptoms. Asymptomatic people are therefore likely to be more contagious. We also know that pre-symptomatic people, those in the early days following infection with Sars-CoV-2, are also highly contagious. Because we are often not aware that we are infected, measures to ensure social distancing and face covering are crucial when it comes to protecting others.
There is some good news on the horizon, though. The first data emerging from vaccine studies show that animals can be protected from Sars-CoV-2 infection, and people do develop hallmarks of protective immunity. This hints that immunological memory is possible. The only way to know for sure, though, is to measure what happens when vaccination volunteers become infected. Ironically, this will take longer in countries that have successfully controlled the virus and have few ongoing infections.
As a viral immunologist, I see immunity in Covid-19 as a puzzle that we have yet to solve. But every week, new publications add new pieces to the jigsaw. When vaccines become widely available, protection will be much easier to assess using serology and lab-based tests. Right now, antibody tests do not confirm protection – it is just too early to know the quantity and type that would be necessary for that. They are still important, however, in charting the virus’s progress through our care homes, hospitals, public transport systems and workplaces (even if they do underestimate those affected). It is therefore vital that people who have agreed to be tested and come back positive are not disadvantaged in any way compared to those whose status is unknown. Without this kind of infection surveillance, much of the hardship of lockdown will have been in vain. – The Guardian
- Dr Zania Stamataki is a senior lecturer and researcher in viral immunology at the University of Birmingham