Something called “immunity debt” has been in the news quite a bit lately. Most recently, because of what looks like a multicountry Mycoplasma pneumoniae epidemic, but before then, in the buzz around larger or earlier outbreaks of hospitalisations, seasonal viruses or “brutal” or “mysterious” colds or a rise in Streptococcal infections or a “tripledemic“, all emerging since the pandemic’s first waves subsided. What is this debt, also called an “immunity gap”, and what might be causing whatever that is?

“Immunity debt” (also called the “immunity gap“; I personally prefer “infection gap”) was a term, applied at the population level, published in the scientific literature in May 2021 (with follow-ups in late 2022 and 2023). In their paper, Cohen and co-authors suggested a rise in the number of people susceptible to, or able to be infected by, pathogens (viruses, bacteria and fungi other than SARS-CoV-2) they’d avoided during the times when protective measures to intervene in and slow the spread of SARS-CoV-2 were in place.

And how long might it be until we get back in balance? Truth is, there’s no rule book to spell that out. We’ll know afterwards. Below is an image from Dr. Katelyn Jetelina’s blog attempting to think the timing through using the recovered\infected\susceptible model as a visual aid.

The interventions that drove down the transmission of SARS-CoV-2 also worked to reduce the transmission of all sorts of other airborne-spread nasties. But what specifically could drive the creation of a bigger pool of susceptible humans, creating an immunity\infection debt\gap?

We sheltered the babies

One new group of susceptibles is the newborn. This may include multiple years of new humans who missed out on exposure to the normal disease-causing viruses and bacteria. To be clear – that’s actually good news for the very young, as the impact of these early infections can be devastating and long-lasting to tiny airways. But at some point, transmission is going to pick up, and children will get infected.

Any member of a household, daycare, kindergarten, school or play centre knows that infected young children are very generous with their secretions. Once one child is infected, that spreads because each little virus factory is a transmission hub that creates a network of new infections. When you have a lot of virus factories, there’s a lot of spread.

None of this is a failure of the immune system, it’s just about the sheer number of people who can be infected and the burst of spread that they cause.

As we experienced with SARS-CoV-2, not everyone is infected at one time during a surge. So these earlier or bigger seasons may last cycle over a couple of years or more until a regular pattern – now with a new viral kid on the block to mix that up – settles into a rhythm.

We protected the new mums

The protective interventions also kept new mothers safe so they also saw fewer infections by all the pathogens. In adults, these infections, yes even those you don’t think you ever have, help ‘top up’ our existing immunity to these pathogens, which we all gained from birth.

For those mothers who breastfed their newborns, there was a likely lower level of protective antibodies transferred via milk and a reduced transfer across the placenta during gestation. This might allow a first infection to have a bigger impact.

Missed vaccination

Another pool of susceptible humans is those who missed out on regular childhood vaccinations during times of isolation. While we don’t have a lot of vaccines against airborne-spread respiratory viruses and bacteria, we are already seeing unusual spikes of infections by those pathogens we can immunise against.

As the community burden of those cases rises, a pathogen amplification system develops where usually few cases of that thing might circulate. That will help spread the infection to older children and adults who may not have seen a vaccine in decades, or who have immune deficiencies, are pregnant and so on.

Time does weary them (levels of antibodies)

Yet another pool of susceptibles is simply created by time passing. Time since the last vaccination. Time since the last infection. We know immunity wanes over time. It doesn’t disappear, and it’s ready for the next challenge to help tone down the severity of that infection, but the human body does knock back the resources it dedicates to each of its many immune responses over time. The length of time also differs. Those with immune system deficiencies, the elderly and the pregnant may all be at greater risk of taking a bigger hit from an infection now.

What else could be causing lots of different viral infections in high numbers?

Nothing?

We do have multi-pathogen seasons every year, and we also have lots of cases of people being infected by more than one pathogen at a time (co-infections). So this isn’t totally new. But the scale of it does seem bigger than normal, it seems to be globally co-occurring and also happening outside of the normal season we assign different respiratory pathogens. And that is why all this is being thought about and new terms are being considered to help discuss it more easily.

Tissue damage provides new opportunities for everyday pathogens

After you’ve had a respiratory virus infect and replicate in you – it leaves damaged cells behind.

Pain from a sore throat, for example, exemplifies damaged tissue. The airways can also be damaged. When this happens, some bacteria and fungi that live around or within us can gain an all-access pass to suddenly less well-defended tissues. And now you have a new infection. Maybe even at the same time as the virus you got first. Maybe starting up as the first one resolves, a changeover that can be imperceptible and feel like a four-week bout of yuck instead of two two-week bouts.

Immune-evading tricks

Every pathogen has a range of tricks to moderate the immune response a human host mounts against them. It’s worth noting this because it’s a major factor in why we are not always sick – because we are always being exposed to pathogens.

Some exceptions are particularly nasty – like HIV and its ability to actually make us immune-deficient. Or the Measles virus, which can take away our immune memory of past infections, resetting our immune clock. Others, like the herpesvirus es stay with us for life, hiding sway from being cleared out and popping back up when the right triggers are pulled.

Apart from some exceptions, though, with a big enough dose, or an underlying issue that increases your risk, most of the pathogens being discussed in this post can be defeated or tempered by our immunity.

SARS-CoV-2 also has its own bag of tricks, and it also seems to be able to persist, especially in the gut tissue, where, for some people at least, it may be tiring out the immune system and contributing to longCOVID’s many unwelcome chronic impacts.

Evolution is constant

The pathogens themselves have also kept mutating. And they ‘live’ and ‘die’ at a much higher turnover than we do – evolution requires death. And this constant change is possibly one of the least often discussed issues. Pathogen evolution can be random (like the mutations), and can also be driven by the selection of more effectively spreading and immune-escaping variants. Pathogens are under evolutionary pressure to escape past immunity. It’s that successful. So it makes sense that if they can keep disseminating, it’s because we either have no specific immunity to a particular pathogen or reduced levels of it to the new variant(s) of the pathogen that’s spreading.

Apart from influenza B\Yamagata virus, the planet is still plagued by all the species of respiratory pathogens that existed before the pandemic (caveat: I haven’t seen a roll call of adenoviruses, rhinoviruses and enteroviruses so…). That’s because countries didn’t concurrently enact sufficient interventions to see pathogen spread completely contained and because, for example, frontline workers still dropped children at care centres to mix and return their household infections in countries with more strict approaches.

So why is everyone sick?

It’s not because COVID-19 results in the destruction of our immune systems. One great way to tell this is because, at the population level, our immunity keeps crushing previous SARS-CoV-2 (and flu and RSV and so on) variants by forcing them to change and reinvent themselves to keep infecting us.

What we’re seeing is the result of the disease burden of so many respiratory viruses opportunistically infecting us. These waves of earlier, larger, nastier-feeling and globally co-occurring (thanks travel) colds will probably settle down. Increased hospitalisations of the very young, the elderly and those at greater risk from the inflammatory stresses put on our system by these pathogens will similarly get onto a new pattern.

In the meantime, we need to do something about the quality of the air we inhale. We could have dramatically reduced these multi-pathogen waves if our gathering places filtered and treated the air we share. If we wore decent P2 or N95 respirators (masks that filter out the airborne particles on which these pathogens hitch a ride), we could better protect ourselves and those around us.

For some reason, I still can’t define, despite being hit on the head with the evidence for why, those we expect to lead and protect us have done next to nothing towards that end. They haven’t funded innovation or installation, they haven’t legislated new standards in light of new evidence nor educated, distilled or communicated the facts in the previous paragraph. Without leadership, it’s so much more difficult to keep ourselves safe in an interconnected, busy and often densely packed world. But we do have the tools.

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