On Aug. 15, a 33-year-old man landed in Hong Kong after flying home from Spain. On his arrival, he was screened for COVID-19. Despite feeling well, he tested positive. It was the second time in less than five months that he contracted the virus.
The case immediately caught scientists’ attention. The man was the first in the world to have a confirmed COVID-19 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 has raised fresh concerns.
Illustration: Constance Chou
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 hospitalized 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 Yale University immunobiology professor Akiko Iwasaki, who has been closely following cases of reinfection. “Essentially, every case is different.”
As only about 25 reinfections have been confirmed worldwide in a pandemic that has infected more than 30 million people, 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 that they are distinct, which 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,” Iwasaki said.
The immune system’s battle against COVID-19 is unleashed in several waves. The first line of defense, the innate immune system, is imprecise but fast. Invading pathogens prompt cells to churn out signaling 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 specialized attacking force. This unleashes T-cells, which destroy infected cells, and prompts B-cells to make antibodies that stick to viruses and stop them from spreading further.
If and when the infection is beaten, the T and B-cells stand down, but the body stores some for years as immune memory that can be recommissioned if the virus tries 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 not only happens, but can cause more serious disease.
In a report on reinfected healthcare workers in India, 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 COVID-19.
“Her immunity wasn’t enough to protect her from the second, more severe infection, despite the presence of neutralizing 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? Are reinfected people infectious to others?
Imperial College London immunology professor Danny Altmann guesses that those who recover from COVID-19 have perhaps 90 percent 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 is right for about two weeks and then it’s completely wrong.”
Reinfections might be worse for a whole host of reasons. The person might have been exposed to more of the virus the second time around, or might simply have been under the weather 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 a second infection 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 Massachusetts General Hospital’s Ragon Institute, examined tissue taken from dead COVID-19 patients.
He looked for structures called “germinal centers” 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 that the patients were unable to generate highly effective, long-lasting antibodies that would fight the virus for years.
He believes that the same problem might also arise in people with milder COVID-19 infections.
“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.
That poses another problem, University of St Andrews social psychology professor Stephen Reicher said.
People who have recovered from COVID-19, and many who falsely believe they had it, might believe that they are protected in a second wave.
“I think it is important, all ways round, to dispel the myth of invulnerability,” Reicher said.
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