So who is immune to Covid-19, and how can we tell?

Who is immune to Covid-19 is the question on everyone's lips as Ireland – along with many other countries – begins to plan its exit from full lockdown.

The answer is not straightforward – and microbiologists, epidemiologists and public health doctors are still searching for crucial information about if and how the immune system will protect those who had the virus into the future.

Dr Fidelma Fitzpatrick, consultant microbiologist at Beaumont Hospital and senior lecturer at the Royal College of Surgeons in Ireland, says the easiest way to understand what is known is to categorise people with Covid-19 into three groups – those with no symptoms; those who get a mild form of the disease; and those who become very ill with Covid-19. "We don't know yet if those asymptomatic patients [now considered to be a much larger group than first thought] who carry and spread the disease have immunity to Covid-19 or not," explains Fitzpatrick.

People who suffer from mild symptoms of Covid-19 such as a cough, headache and aches and pains are most likely to be protected from catching Covid-19 in the near future because their bodies’ immune systems fought the disease (developing antibodies in the process) to the extent that they didn’t develop more severe symptoms.

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“As far as we understand, people need to be in good health and possibly have a certain genetic predisposition which allows them to have only mild symptoms of Covid-19 which also allows their immune system to develop antibodies against the disease in the future,” says Fitzpatrick.

People who develop severe respiratory symptoms of Covid-19 – typically older people and those with underlying conditions or weak immune systems – also develop antibodies which should protect them from developing the disease again.

However, it’s more complicated.

“The initial immune system response hasn’t worked for these patients so their immune systems go into overdrive causing lots of inflammation which results in viral pneumonia,” says Fitzpatrick. In spite of these more severe symptoms, it is expected that the patients who recover from these more severe symptoms of Covid-19 will also develop antibodies which will protect them against future infection.

People's personal health status before they catch Covid-19 plays a part in the development of antibodies

To complicate the situation further, people's personal health status before they catch Covid-19 plays a part in the development of antibodies – which will provide immunity to the disease. One widely quoted study of 175 patients with mild symptoms in China found that 70 per cent of patients developed a strong antibody response; 25 per cent developed a low antibody response; and 5 per cent had no antibody response which means that they will not be protected from catching Covid-19 in the future.

The third part of understanding immunity to Covid-19 that scientists don’t know yet is how long the immunity to Covid-19 will last in those who do develop sufficient antibodies.

According to Prof Mary Horgan, consultant in infectious diseases at Cork University Hospital: "We don't know exactly how long people who have had Covid-19 will be protected from getting it again but we do know from other similar types of coronaviruses – severe acute respiratory syndrome, or Sars, and Middle East respiratory syndrome, or Mers – that immunity can last for up to three years."

As the world waits for the development of a vaccine against Covid-19, the widespread availability for antibody tests to find out who has immunity to the disease – and can therefore move freely in society again – is a crucial next step. Some countries such as Germany are investigating how results from antibody tests could provide people with an "immunity passport" meaning that those who had recovered could return to work.

Like everything else about this disease, finding a reliable antibody test won’t be easy either. “We need antibody tests that are validated specific to Covid-19 [ie, tests which won’t confuse Covid-19 with other earlier coronaviruses] and sensitive enough to pick up antibodies to it,” says Horgan.

In Northern Italy, Lombardy and Emilia-Romagna started offering antibody tests to Covid-19 to healthcare workers and other frontline workers on April 23rd. Italy plans to launch national antibody testing with a sample of 150,000 people on May 4th, with the intention to extend it to 4 million people by the end of May.  The antibody test from US company Abbot Laboratories is deemed to be specific to Covid-19, with a claimed sensitivity of over 99 per cent, 14 days or more after the last symptoms of Covid-19.

There is no evidence that having had the [Covid-19] virus would guarantee immunity and it seems low percentages of people have developed antibodies

There are more than 60 antibody test kits in development around the world. They are usually simple blood tests which look for the antibody molecules the immune system makes when someone is infected with a disease. But, how reliable these are is not yet known, and many of them have been developed so quickly that accuracy rates are based on a small number of test cases.

On April 18th, the World Health Organisation (WHO) put a brake on people's expectations that antibody tests would help countries move out of lockdown measures. "There is no evidence that having had the [Covid-19] virus would guarantee immunity and it seems low percentages of people have developed antibodies," said Dr Mike Ryan, head of WHO's emergencies programme. Regardless, in some parts of the US, antibody tests have been rolled out despite a lack of reliability and validation.

Last Friday, the WHO warned against issuing “immunity passports”, saying there is no evidence people will be protected from a second infection. The idea of issuing some form of certificates to people who have been sick with the virus - on the assumption they would be immune to reinfection - has been gaining ground in many places as authorities cast around for ways out of socially and economically devastating lockdowns. But in a scientific briefing note, the WHO warned: “At this point in the pandemic, there is not enough evidence about the effectiveness of antibody-mediated immunity to guarantee the accuracy of an 'immunity passport' or 'risk-free certificate'. People who assume that they are immune to a second infection because they have received a positive test result may ignore public health advice. The use of such certificates may therefore increase the risks of continued transmission.”

There have been reports, including from China and South Korea, of patients who appeared to have recovered from the disease testing positive again. There are several possible explanations for those results. Jeong Eun-kyeong, director of the Korea Centers for Disease Control and Prevention, said rather than patients being reinfected, the virus may have been “reactivated”. False test results could also be at fault, other experts said, or remnants of the virus could still be in patients' systems but not ones that pose a danger to the host or risk infecting others.

The risk of antibody tests giving "false positives" (ie signalling the person had Covid-19 when they didn't) remains substantial. Scientists at Trinity College Dublin (TCD) are planning to test several new antibody test kits to find out which ones will be the most reliable. It can take between three and four weeks after symptoms appear in a person for antibody levels to be detectable in an antibody test.

Only when about 70 per cent of the population has immunity to Covid-19 will we all be safe again to lead normal lives

Tomas Ryan, associate professor at the School of Biochemistry and Immunology at TCD, says for Ireland to emerge from the lockdown without risking a second wave of infections requires two strategies. Writing in The Irish Times in mid-April, he outlined this approach. The first strategy is to "search, identify and isolate all potential cases and contacts" by widespread testing for the virus and the second is to develop "antibody-based population testing" to assess the population's overall immunity.

Perhaps only when about 70 per cent of the population has immunity to Covid-19 – either through developing antibodies from having the illness or by being vaccinated against it – will we all be safe again to lead normal lives. “A vaccine is the safest way to get herd immunity but, in these circumstances, antibody testing on a massive scale is the only way we will know who has developed immunity to Covid-19 – until a vaccine is developed,” says Horgan.

Prof Peter Doran, director of clinical research at University College Dublin, adds: "Antibody testing will be a game-changer in our efforts to stem the Covid-19 pandemic, as it will reveal to us those individuals who have previously been infected. This is particularly important given that a large number of infected people remain asymptomatic. Such tests are likely to be widely available once they have been rigorously evaluated in samples from patients who have recovered from Covid- 19."

Alongside the continuing diagnostic testing for Covid-19 and contact tracing, the National Public Health Emergency Team (NPHET) is continuing to review the role of antibody testing to check what per cent of the Irish population could have immunity to Covid-19.

Once antibody tests which have been validated specific and sensitive enough to pick up antibodies to Covid-19 have been developed, the questions will be how and where can people get tested for immunity. Will our GPs or community-based hubs already set up for diagnostic testing for Covid-19 be used?

Or will we be able to get home tests to test ourselves to see if we are immune to Covid-19 and able to move freely about in our communities again?

Read: 'It's fantastic that I got through Covid-19 so well'