A fifth confirmed Covid reinfection is a big blow for herd immunity

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On May 31, a 25 year old man from Washoe County, Nevada presented to an urgent care centre with an array of common viral infection symptoms including fever, headache, dizziness, and nausea. A couple of days later he was diagnosed with Covid-19.
That in itself would be a relatively unremarkable story. But what made the case unusual was that the same patient had also tested positive for the Sars-CoV-2 virus six weeks earlier, before apparently recovering.

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It soon came to the attention of Mark Pandori, director of the Nevada State Public Health Laboratory, and a scientist who was particularly interested in the growing number of reports of people apparently becoming reinfected with Covid-19. In order to prove that the man had actually caught the virus twice, rather than just a single continuous infection, Pandori obtained the swabs from the first and second tests, and sequenced the viral genomes from each sample.
The results, which are published in The Lancet Infectious Diseases journal, appear to clearly indicate that the man had indeed been infected with two different strains of Sars-CoV-2, the virus that causes Covid-19. So far it is the fifth person to have definitely caught Covid-19 twice. The four other cases were recorded in Belgium, Ecuador, the Netherlands and Hong Kong.
“What these cases are showing is that there’s no such thing as invulnerability if you’ve had this virus,” says Pandori. “For anybody that has had Covid-19, it doesn’t mean that you’re definitely immune and there is no further harm that can come to you. This implies that you can get it again.”
For many immunologists, this is not entirely surprising. After all humans are notoriously prone to repeatedly catching various members of the coronavirus family. Back in the 1980s, a series of experiments demonstrated that people who had been infected with one of the seasonal coronaviruses which cause the common cold could be deliberately reinfected a year later. More recently, scientists from the Netherlands used an extensive biobank archive to show that human immunity to such coronaviruses tends to be very limited.

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“They got out every tube of serum going back 35 years and said, ‘Let’s work out how many of these people became immune to the common cold coronaviruses,’” says Danny Altmann, professor of immunology at Imperial College London. “And the answer was, you can get the same coronavirus, year in, year out, forever. Your antibodies are never really sustained long enough to keep you safe.”
There are a few reasons why humans might be susceptible to reinfection with Sars-CoV-2. One might be that the body doesn’t produce sufficient levels of disease-fighting neutralising antibodies the first time round to, or because the individual encounters a newly evolved strain of the virus and their existing antibodies offer little protection.
Pandori points to an intriguing and as yet, unpublished study on the medRxiv preprint server, in which scientists at the Swedish Medical Center in Seattle delved into the reasons behind another case of Covid-19 reinfection. They found that while the patient produced neutralising antibodies in response to the first infection, they had little or no effect the second time round.
“Both our paper and this study showed genetic differences between the viruses which caused the two cases,” says Pandori. “This might imply that SARS-CoV-2 is evolving at enough of a rate to establish reinfection. Immune responses that were elicited early in the pandemic may have less power against the viral strains circulating now.”

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While officially there have only been five cases in total of people catching Covid-19 twice, scientists believe the real figure is much higher. But estimating the true number of reinfections is logistically complicated and often impossible, says Altmann. “Proving someone has tested positive twice first requires the first testing station to have retained the swab sample in a good enough state so the virus can be sequenced. Then you’ve got to get that to a lab, and match it with a swab from the second infection so that can be sequenced too, and then you can prove to the world that these are two different virus attacks. How often is that going to happen?”
In reality Altmann estimates that around 10 per cent of the people who have already contracted and had symptoms of Covid-19, are susceptible to getting it again. He says that this estimate comes from a number of as yet unpublished datasets which suggest that approximately 90 per cent of people who have had the virus should have sufficient levels of neutralising antibodies to protect them against the currently circulating strains for the next year.
Of course 10 per cent of Covid-19 cases is still a substantial figure, in the UK alone it would imply that approximately 61,800 people are vulnerable to being reinfected. If Altmann’s estimate is accurate – and such evidence has yet to be validated in a peer-reviewed journal – it would be a severe blow against the idea that populations could achieve herd immunity against the virus.
“What we’ve got to do, is get a robust set of vaccines fairly fast, which would bypass this problem as vaccines don’t work in the same way as a natural infection response does,” says Altmann.
But while vaccines do tend to offer more durable and better protection than the body’s natural immune responses, the emerging cases of Covid-19 reinfection still pose various questions for vaccine development.
As Richard Malley, a paediatric infectious-disease specialist at Boston Children’s Hospital, points out, it is far easier to make effective vaccines against viruses where the initial infection results in lasting immunity. “Some of the very best vaccines ever developed target measles, mumps, rubella, chickenpox and yellow fever. [These are] diseases where once infected, an individual is extremely unlikely to ever develop the disease again,” he says. “That said, it is still possible to develop vaccines for diseases that people can get more than once, but in these cases, the requirement for the vaccine is to induce immunity that is superior to that generated by natural infection. It is certainly possible, but harder.”
However, over the coming months, scientists are likely to learn far more about Covid-19 reinfections due to a number of ongoing studies such as Public Health England’s SIREN project which is monitoring more than 10,000 healthcare workers to ascertain their risk of reinfection during the second wave. This will inform vaccine developers as to whether people become particularly vulnerable once their antibody levels drop below a certain threshold, and whether booster shots may need to be part of any vaccination regime.
Another key question to answer will be the proportion of individuals who suffer a more severe case of Covid-19 when reinfected. Of the five officially reported cases of Covid-19 reinfection, both the Nevada patient in Pandori’s study and a patient in Ecuador suffered worse outcomes the second time round.
Pandori says that there are a variety of plausible reasons for this, ranging from being exposed to a higher viral load the second time, to a rare phenomenon called antibody-dependent enhancement whereby the immune system malfunctions and the presence of antibodies actually make a subsequent infection worse. However, because so few cases of Covid-19 reinfection have been studied so far, it is hard to draw conclusions.
For the time being, the most significant impact of these new reports is likely to be a psychological one. While Public Health England have urged the public to continue taking precautions and maintain social distancing, even if they contracted and recovered from Covid-19, the prevailing mood has been that surviving a Covid-19 infection offered the silver lining of long-term immunity.
Now there is increasing evidence that this is not necessarily the case. “These findings mean that if anybody tells you we’ve got to do nothing, and hope for the best with herd immunity, they’re kidding you and themselves and being very dangerous,” says Altmann. “The only hope really is a good vaccine. Vaccines can give you very sustainable immunity that can last you for many many years and keep you safe.”
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