On 15 August, a 33-year-old man landed in Hong Kong after flying home from Spain. On arrival, he was screened for coronavirus. Despite feeling well he tested positive. It was the second time he had picked up Covid-19 in less than five months.

The case immediately caught scientists’ attention. The man was the first in the world to have a confirmed coronavirus reinfection and there were positives to take from the report. First and foremost, he was asymptomatic. Although reinfected with Sars-Cov-2, his immune system swung into action fast and contained the virus without him knowing.

Many researchers took heart from the case, but since the patient came to light a flurry of reinfections around the world have raised fresh concerns. Within days of the Hong Kong case being made public, doctors in the US reported that a 25-year-old man from Reno, Nevada, had been hospitalised with a Covid-19 reinfection after shrugging off an earlier brush with the disease. More cases soon followed. While most infections were no worse the second time around, a good number cropped up – in the US, the Netherlands, Ecuador and India – where the reinfection was more severe.

“It’s really hard to find a pattern right now,” said Akiko Iwasaki, a professor of immunobiology at Yale University who has been following cases of reinfection closely. “Essentially every case is different.”

So far, only two dozen or so reinfections have been confirmed worldwide in a pandemic that has infected more than 30 million people. For now at least, reinfection seems uncommon. But scientists point out that confirming reinfection is no easy task and many cases are missed.

To confirm a reinfection, scientists must examine the genetic code of the virus from each round of illness and prove they are distinct. That means having access to both sets of swabs and the wherewithal to do whole genome sequencing. Even in hospitals where the capacity exists, such tests are rarely done. Reinfected patients simply go unnoticed or unreported. “There is probably a lot more than we are seeing,” said Iwasaki.

The immune system’s battle against coronavirus is unleashed in several waves. The first line of defence, the innate immune system, is imprecise but fast. Invading pathogens prompt cells to churn out signalling proteins called cytokines which call in an army of white blood cells that engulf and disrupt the virus.

Next to gear up is the adaptive immune system, a more specialised attacking force. This unleashes T-cells, which destroy infected cells, and prompts B-cells to make antibodies that stick to viruses and stop them spreading further. If and when the infection is beaten, the T- and B-cells stand down, but some should be stored in the body for years, an immune memory that can be recommissioned should the virus try again.

Given the complexity of the immune response, it is no surprise that scientists are struggling to unravel why reinfections occur. Blood tests on patients reveal that virus-disabling antibodies can wane after a few months, particularly in those with mild or no symptoms. But even with healthy levels of antibodies, reinfection can not only happen, but cause more serious disease.

In a report on reinfected healthcare workers in India, Prof Jayanthi Shastri and her team at Kasturba hospital for infectious disease in Mumbai describe a 25-year-old nurse who suffered more with a reinfection two months after her first battle with coronavirus. “Her immunity wasn’t enough to protect her from the second, more severe infection despite the presence of neutralising antibodies,” Shastri said.

The finding, and similar cases, has refocused attention on a handful of questions that scientists are struggling to answer. What does protective immunity look like? How long does it last? Do some patients fail to mount the right response? Does the virus damage the immune system? And are reinfected people infectious to others?

Danny Altmann, professor of immunology at Imperial college in London, guesses that those who recover from Covid-19 will have perhaps 90% protection for a “fair while”. But how long is that? “I would bet my house on you being safe for possibly a year but not much longer,” he said. “The problem is that whenever an immunologist says anything about Covid immunity to a journalist, it’s right for about two weeks and then it’s completely wrong.”

Reinfections may be worse for a whole host of reasons. The person might have been exposed to more virus the second time around, or may simply have been under the weather already when the virus struck again.

Another possibility is so-called antibody-dependent enhancement – a glitch in the immune system where antibodies help an invading virus rather than hinder it. This is seen in dengue fever where second infections can be far more dangerous than the first.

Yet another possibility is that the virus harms T-cells, in some patients at least. “We need to study the T-cells,” said Swapneil Parikh, who worked with Shastri on reinfected hospital workers. “Is the virus doing something to the immune system that is setting you up for more severe infections?”

The virus can certainly disrupt the immune system. In August, Shiv Pillai, an immunologist at the Ragon Institute of Massachusetts general hospital, examined tissue taken from dead Covid-19 patients. He looked for structures called “germinal centres” in the spleen and lymph nodes. These are where B-cells go to develop antibodies before they are stored in the immune system’s memory. Pillai failed to find any, suggesting the patients were unable to generate highly effective, long-lasting antibodies that would fight the virus for years.

He believes the same problem may arise in people with milder Covid-19 too. “If we want antibodies that will persist for a few years and protect us, it’s not clear that’s going to happen,” he said. The good news is that a vaccine should not cause the same problem as the virus. “I don’t see why the vaccines won’t work. They may not be fantastic, but I believe that’s what’s going to protect us,” he said.

If the virus spreads further through the autumn and winter, Iwasaki expects to see more reinfections, with some patients infectious enough to pass the virus on.

According to Stephen Reicher, professor of social psychology at the University of St Andrews, and a member of the behavioural science subgroup of Sage, that poses another problem. People who have recovered from Covid-19, and many who falsely believe they had it, may believe they are protected in the second wave. “I think it is important, all ways round, to dispel the myth of invulnerability,” he said.


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