Original article: Why scientists are rethinking the immune effects of SARS-CoV-2
Citation: BMJ. 2025;390:r1733
Summary
This feature article discusses how SARS-CoV-2 may be altering human immunity, challenging the popular “immunity debt” theory that blames rising non-covid infections solely on reduced exposure during pandemic restrictions.
◯ Limits of the immunity debt theory
Not all pathogens have shown uniform rebounds. Data suggest that COVID-19 survivors are at greater risk of bacterial and viral infections compared with influenza or RSV survivors.
◯ Post-COVID immune alterations
Studies indicate persistent immune scars such as T cell exhaustion, immune dysregulation, and reactivation of latent viruses like EBV and VZV.
◯ The “immune reset” hypothesis
Similar to measles-induced immune amnesia, SARS-CoV-2 may partially reset immune memory, leaving individuals vulnerable to previously controlled infections.
◯ Clinical evidence
COVID-19 patients, even non-hospitalized, have higher rates of secondary infections, antibiotic prescriptions, and sepsis. Large cohort studies confirm elevated infection risks for up to a year.
◯ Ongoing debate
Some public health leaders dismiss the idea of widespread immune impairment, but emerging evidence points toward subtle yet significant long-term immune changes that may impact global health.
Hello everyone. This is Kutsu Acadea. Okay, let’s dive right in. We’re going to talk about a mystery that I’m sure a lot of you have noticed over the last few years. This quote here from a clinical immunologist, it just perfectly captures this feeling that’s been going around. It really does feel like everyone everywhere is getting sick way more often, doesn’t it? And you know, it’s not just a feeling. The data box it up. We’ve seen reports surging with all sorts of bacterial infections and even flare-ups of old viruses. So, the big question is why? What is going on? That’s exactly what we’re going to dig into. We’re going to investigate the leading scientific theories that are trying to piece this whole puzzle together. So, to really get a handle on what’s happening, we’ve got to rewind a little bit. Let’s go back to that time when all the pandemic restrictions started to lift. Almost right away, this really simple, almost intuitive theory popped up to explain why suddenly everyone seemed to be catching everything. And that first big idea was called immunity debt. You know, on the surface, it makes a lot of sense, right? I mean, we spent a couple of years wearing masks, staying away from each other. We just weren’t getting exposed to all the usual bugs, the common colds and flu. So, the theory goes that our immune systems kind of got, well, lazy, out of practice, and then bam, restrictions lift and we get hit with everything all at once. It was a really simple idea, and it pretty much became the go-to explanation for a while. But as time went on, the sickness didn’t really stop. These waves just kept coming. And that’s when scientists started to look a little closer and wonder, hm, is immunity debt really the whole story here. And pretty soon, some serious cracks started to show up in that theory. Yeah, the whole immunity debt ideas started to look a little shaky when the data just wasn’t adding up. For starters, really serious infections like group A strep, they just kept rising long after we’d stopped all the major precautions. If it was just a debt, you’d expect this one huge rebound and then things would level out, right? But that’s not what happened. And another thing, the rebound wasn’t even across the board for all pathogens. But here’s the real kicker. A lot of the infants and toddlers getting sick, they weren’t even born during the lockdowns. So, how could they possibly have an immunity debt? All these inconsistencies really forced researchers to start looking for another explanation. So with those cracks in the first theory, a lot of scientists began to turn their attention to a new and maybe more obvious suspect, the CO 19 virus itself. The whole hypothesis started to shift. It wasn’t about what we weren’t exposed to anymore, but about the direct impact of this one massive virus that pretty much everyone was exposed to. And this is a really key point. The conversation basically shifted from immunity debt to something called immunity disruption. So the idea isn’t that our immune systems are just undertrained. No, the new theory suggests that the SARS KV2 virus might have actually changed our immune systems in a fundamental way, maybe leaving behind some lasting changes or what some scientists are even calling scars. So this idea of scars, it really focuses on our tea cells. You can think of tea cells as the memory bank of your immune system. They’re the ones that remember old infections so you can fight them off faster next time. The worry here, the core of this new theory is that CO might actually be messing with that memory bank, making us more vulnerable to all sorts of other bugs. So, what’s the evidence for this? What are the clues? Well, one of the first big clues comes from something that scientists have actually seen before with other viruses like measles, and that’s the reactivation of dormant viruses. Now, what does that mean? These are viruses that can just hang out in your body totally quiet for years and years, kept in check by a strong, healthy immune system. For example, a study in 2023 looked at the Epstein bar virus, that’s the one that gives you mono, and what they found was wild. It was reactivating in people who’d had CO at more than double the rate of people who hadn’t. That’s a huge red flag. It really suggests that something about the co infection was weakening the immune system’s ability to keep that old virus under wraps. And it wasn’t just a one-off with the mono virus. Nope. Another study found that people over 50 were 15% more likely to get shingles after a co diagnosis. Now, scientists think this is tied to something they call TE-C cell exhaustion. Just imagine your tea cells are like little security guards. After a huge drawn out fight with a major intruder like CO, some of those guards just get completely worn out. They’re exhausted. And when they’re exhausted, they’re not as good at keeping those other old viruses in their cells. And get this, the evidence is pointing to the fact that these effects can stick around long after you’ve recovered. I’m talking a massive study of US veterans that found they had higher rates of all sorts of infections, bacterial, viral, fungal, for up to a year after their co infection. Then there’s another study suggesting something even deeper. That the virus might be able to reprogram our bone marrow. That’s our body’s factory for immune cells. And it could be skewing them towards a state of constant lowgrade inflammation. And maybe the most amazing finding of all, researchers found bits of the virus still being actively fought by te- cells in gut tissue 2 years later. That’s just incredible. Okay, so I want to be really clear about something here. This is not a settled case. Not at all. This is still a really hot and very important debate happening among scientists and there are some really strong arguments on both sides of the issue. So on one side of the argument you’ve got public health officials like Dr. Ashish Ja and his perspective is that for most people the vast majority co doesn’t actually cause any lasting immune damage. He argues that a lot of the talk about it is based on bad information maybe even misreading the scientific data. But then on the other side, you have immunologists who are in the lab studying the stuff at a cellular level. People like Dr. Tim Henrik, and they’re seeing a completely different picture. They’re observing clear signs of a disrupted immune response. Things like that inflammation and te- cell exhaustion we talked about, even in people who feel totally fine and have no long-term symptoms. And this quote here from Professor Ako Iwasaki really, really gets to the heart of why this is so hard to figure out. See, in science to prove anything, you need a control group. You need a group of people who weren’t exposed to the thing you’re studying. So, you have a baseline for comparison. But her point is with CO, who’s the control group? The entire world has pretty much been exposed. It’s almost impossible to find anyone who hasn’t been touched by this. So, in a way, we’re all the subjects in this massive global experiment. So, where does that leave us? Well, the debate is absolutely still raging. Is what we’re seeing just a simple case of immunity debt? Or is it something more complex, this immunity disruption caused by the virus itself? Or maybe it’s a mix of both? And finding the answer isn’t just for the science books. It’s really, really important because as we learn more about the lingering effects of viruses, it forces us to ask some huge questions about the future. You know, how is this going to change our whole approach to public health? And how do we get ready for whatever comes next? Ksuo Academia. Please subscribe to our channel and give us a thumbs up.
