Immunity debt: does it really exist? | Science

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The deaths of at least 190 people, including 30 children, from the invasive bacterial infection group A streptococcus, or strep A, are the most extreme consequences of a wave of winter infections that have seemingly left most of the country coughing and sneezing. The parlous state of the nation’s health has prompted suggestions that we are now paying an “immunity debt” incurred by the reduction of common infections during the Covid-19 lockdowns of 2020 and 2021. But experts seem divided about whether the debt concept is genuine, let alone whether it explains the prevalence of non-Covid afflictions.

As with so many of the debates about the outcomes of the pandemic, there do not appear to be simple answers – but no shortage of self-proclaimed “experts” ready to give them anyway. While there are good reasons to believe that the measures taken to reduce the spread of the coronavirus have broader implications for common infectious diseases, there is no one-case-fits-all explanation for the spate of winter bugs, much less any obvious conclusions to be drawn about pandemic management.

Are the infection rates really so unusual anyway? Cases of strep A and associated scarlet fever certainly seem unusually high, with 37,068 recorded cases of the latter up to 8 January, compared to 4,490 at the same point in the earlier high season of 2017-18. But whether there is an anomalous prevalence of common infections across the board is less clear. “For some of the infections, we don’t really know,” says Petter Brodin, professor of paediatric immunology at Imperial College London.

Every winter, there is an upsurge in common infections such as flu, colds (caused by various viruses) and respiratory syncytial virus (RSV), which produces cold-like symptoms. Bacterial infections follow a similar seasonality, according to Michael Levin, professor of paediatrics and international child health at Imperial because they tend to take opportunistic advantage of an immune system weakened by a virus. RSV in infants and young children, for example, sometimes leads to bronchiolitis, an infection of the respiratory tract that can be serious.

At this time of year, “having hospital beds filled with children and adults with viral disease and pneumonia is not unusual”, says Levin. But although there is as yet little hard data, he adds that “there is an impression that we are having an unusually severe winter with RSV, flu and adenovirus”, the last of which causes cold-like symptoms. He adds: “We’re seeing increased numbers of children with severe bacterial infections – there is definitely more streptococcal infection around.” There are similar reports across North America, while unusually high levels of RSV in children reported in Australia and New Zealand in mid-2021 provoked the first mentions of Covid immunity debt. Brodin agrees that something seems unusual both in the timing and the numbers of infections. In Sweden, where he was working until moving to Imperial in October 2021, the incidence of RSV was markedly unusual last year too.

If that is the case, what is the cause? “Here we enter the realm of guessing and speculation,” says Levin. It’s not clear that there is a general answer. “Every bug has a different dynamic,” concurs Brodin. Flu surges across the globe, driven largely by temperature changes and people’s travel behaviour, whereas RSV is present all the time in the population and usually peaks about November to December in the UK. The incidence of such infections also depends on how many children are born each year, since newborns have essentially no immunity.

Our immune systems need exposure to pathogens to maintain a good level of resistance. Many common infections such as colds are caused by endemic viruses and bacteria that people often carry asymptomatically because their immune systems keep the pathogen in check. For example, many people carry the meningococcal bacteria that cause meningitis, but only about one in 50,000 were, before vaccines, at risk of getting ill from them. “The normal state for most of these things is asymptomatic carriage,” says Levin.

Such symptom-free, low-level infection can prime the immune system to ward off another infection months or even years later. “Children and adults do build up a repertoire of immunity from exposure,” Levin says – as every parent knows, young children in particular are constantly exchanging common pathogens. But such immunity generally wanes, so if you haven’t been exposed for some time, for example, because of social distancing and lockdowns during 2020 and 2021, you will be more susceptible. “It’s plausible that we may now have a population that has met fewer common viruses and is therefore more susceptible,” says Levin. Moreover, if fewer people have such immunity, there will be more transmission in the population.

“Children normally catch scarlet fever in their first year at school, if at all,” says Shiranee Sriskandan, professor of infectious diseases at Imperial. “Scarlet fever rates plummeted during 2020-2021. Therefore, school-age children may not have built up immunity to strep A, so we now have a much larger cohort of non-immune children.” A study last June reported that, because of reduced transmission of common respiratory viruses during the pandemic, breastfeeding infants were being passed fewer protective antibodies from the mother.

But whether there is a generalised immunity debt is less clear. How long post-infection immunity lasts varies from one virus to another. And for flu viruses, infection in one season may or may not offer protection in the next, depending on how closely related the two strains are. Levin says that in many cases we don’t really know how much repeated exposure is needed to sustain immunity – for some diseases, such as smallpox and measles, just one infection generally gives lifelong protection.

Another reason that has been proposed for enhanced infections this season is that Covid-19, which most of the population has now experienced at least once, has itself weakened some people’s immune systems. But this will probably not be widespread, if it happens at all. While there is evidence of immune dysfunction persisting for many months in some people who catch Covid, this is not so much a weakening of immunity as a problematic overactivation. A study published last January by Prof Gail Matthews, an infectious diseases physician at the University of New South Wales in Australia, and her colleagues showed overactive immune function up to eight months after Covid infection in some people. “The most likely reason for this is some level of viral persistence that the immune system is recognising as foreign and still reacting to,” Matthews says. But she doubts that there is any evidence of widespread Covid-induced immune impairment.

Lockdown was the right strategy for a new disease with a totally susceptible population and probably saved thousands of lives

Michael Levin, Imperial College London

Brodin has seen similar Covid-related immune dysfunction. He and his co-workers have studied children with multisystem inflammatory syndrome, a rare but serious condition in which an extreme response a few months after infection has to be treated with immunosuppressants. He says that for some people with long Covid too: “There is clearly something wrong with the way the immune system continues to be activated.” But whether any such problems arise for the majority of people who have mild Covid symptoms is far less clear, he says. “There’s nothing that suggests that, although we can’t rule it out.”

Lockdowns and social distancing do seem to have reduced infections such as flu and RSV during the pandemic. But if it turns out that those measures have contributed to higher rates of such infections now, what conclusions should we draw? Opponents of lockdowns say that it highlights another of their flaws, for which we are now paying a heavy price.

That position makes little sense. There is compelling evidence that lockdowns and social distancing saved lives, especially while vaccines were still not available. A day or two in bed with a bad cold seems a small price to pay for that. A small minority of researchers have, however, questioned whether lockdowns really made much difference to the spread of Covid. Infectious-disease epidemiologist Sunetra Gupta of Oxford University asserted in the Daily Telegraph that lockdowns do little to slow the spread of an epidemic disease such as Covid-19 but have much more impact on endemic diseases such as colds and RSV. But Brodin is dismissive of such a crude division into epidemic versus endemic diseases. “It’s incredibly far-fetched to say that is the uniform solution,” he says.

Besides, he adds, how then to explain that RSV is also running riot now in Sweden, which famously eschewed lockdowns and kept schools open? Those who have noisily championed the Swedish approach to the pandemic can hardly argue that it would have made any difference to our alleged immunity debt now. In short, Brodin says, it is much too simplistic to say: “What we’re seeing in children’s hospitals is simply the result of lockdown.” Besides, Levin adds: “Lockdown was an essential public health measure. It was the right strategy for a new disease with a totally susceptible population and probably saved thousands of lives.”

A much more fruitful response to the surge in infections, says Brodin, is to “be thinking about how we develop better vaccines and get people to take them”. We should be developing and rolling out vaccines against flu (for which multistrain “universal” jabs are now being trialled) and RSV (for which a vaccine is on the near horizon) much faster, as well as thinking more seriously about non-pharmaceutical interventions such as wearing masks. “It seems absolutely insane to me that we should get on a packed tube at rush hour and there will be people sneezing and coughing and not wearing a mask to protect others,” says Levin. “In Asian countries, you have always worn a mask if you have a cold.” He adds that we should also stop encouraging ill people to go to work and continue to advise hand washing and good hygiene. Flu, for instance, is spread mostly by people touching infected surfaces and then their eyes. Such measures “could greatly reduce the burden of infection in the population”, he says.

But vaccines are key. “Many of these severe diseases are vaccine-preventable and we should be ensuring that as many of the population as are susceptible are protected,” says Levin. If we rely on natural infection to build up immunity, though, isn’t that better than getting vaccinated? No, says Prof Peter Openshaw, who heads the infection programme of the Biomedical Research Centre at Imperial. The immune response a vaccine awakens is “just as ‘natural’ as the response you get to the virus, sometimes even better, and certainly less dangerous”.

“I can’t think of an example of a viral infection being better than getting vaccinated,” Openshaw adds. What’s more, the point of a vaccine is to protect those who would otherwise probably develop severe disease – and predicting who those people are is not always possible. “We vaccinate all to protect the few, because we can’t identify the vulnerable,” says Levin. Covid should have taught us that.

Casting this debate in terms of an immunity debt is therefore potentially misleading, as it implies that this is a zero-sum game: you have to keep paying with infections to stay in credit. Vaccines can simply cancel the “debt”. Who wouldn’t want that?

This article was amended on 15 January 2023 to provide the most recent data for strep A and scarlet fever, up to 8 January; a previous version only had the figures up to 11 December.

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