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Does COVID-19 Mess with the Immune System?

Somewhere between alarmism and dismissal lies what we know about the long-term consequences of a COVID infection on our body’s ability to fight off infections

Have you heard that, apparently, COVID-19 is “airborne AIDS?”

“I think that that epithet is horrifying and beyond offensive,” Edward Nirenberg tells me. He is a science communicator with a degree in biochemistry who focuses his communication efforts on vaccines and COVID-19. “It categorically isn’t. It’s not what the data show.”

The online discourse over the pandemic, which is now entering its fourth year, has become irreparably polarized. One side, craving a return to normal, downplays the severity of the disease and impugns the worth of our interventions to contain it. The other side, desperate for policy action, latches onto any early signal that the virus may mess with the human body in new ways to ring the alarm.

Which brings us to the unfortunate phrase “airborne AIDS,” which has spread over social media. Does a COVID-19 infection, even if mild or asymptomatic, create an immune deficiency that puts us at risk for future infections?

Alarmist headlines

In order to understand something, we must study it. Right from the start of the COVID-19 pandemic, scientists started looking at the blood of patients with the disease to understand how their immune system was reacting to the virus. What some were seeing was out of this world. Professor Dawn Bowdish, Canada Research Chair in Aging and Immunology and a professor of medicine at McMaster University, vividly remembers the first samples from the intensive care unit next door that her post-doctoral fellow brought her. That fellow told her, “This doesn’t look like human blood.” Bowdish had seen what the blood cells of patients in critical care looked like, but this was a different story. It turns out that people with a severe COVID-19 infection, especially if they didn’t receive the vaccine, have significant changes in the generation of their immune cells, which is “really unusual for an infectious disease,” she adds.

As people started recovering from their infections, with some developing long-lasting symptoms, researchers began to scrutinize their immune systems post-COVID. The papers that were published following this exploratory hunt for abnormalities can easily trigger anxiety. We can read about a decrease, eight months post-infection, in the number of dendritic cells, those spies that take a snapshot of our immunological battlefield and help decide if a more targeted response is needed. We can read about an increase in T cells expressing a marker, PD-1, that apparently signals their exhaustion. We can read about expansions, decreases, imbalances, suppressions, even accelerated biological aging of our immune system, none of which is encouraging.

Part of the reason why these changes are being unearthed is that scientists are looking for them. It’s safe to say that no infectious disease has received the kind of concentrated and multidisciplinary attention that COVID-19 has. You’re going to find something when you go looking for it.

But all of these molecular and cellular changes have to be put into context. That PD-1 marker sticking out of T cells after a COVID infection, for example, is not the surrender flag you might think it is. “PD-1 expression is a marker seen on exhausted cells,” Professor Sheena Cruickshank, an immunologist at the University of Manchester, tells me, “but it is also a marker that cells express when activated.” Our T cells, important fighters in our more specific immune response to infection, can become exhausted, such as in malaria when the infection recurs, and this exhaustion is a way for the body to protect itself from collateral damage. But we can’t look at a single marker on the surface of our T cells and declare them exhausted and forever unable to fulfill their function.

In the era of social media, however, preliminary laboratory findings catch the attention of influencers and can cause needless panic. Nirenberg remembers one paper from late last year that was making the rounds: it reported a reprogramming of monocytes, reinforcement cells in our immune system, in people in the acute phase of a COVID infection. This change made them worse at sensing infections and better at promoting clotting. “I heard a lot of alarmist headlines like, ‘SARS-CoV-2 is destroying our immune system,’ but those kinds of changes that the authors report, you can see them with the flu vaccine.” Sure enough, a week later, a paper came out that contradicted these fatalist headlines by showing that men who had recovered from COVID had a better response to the flu vaccine, in part because of their monocytes. Their immune system was certainly not destroyed.

We are all, by now, familiar with the Swiss cheese model of protection, which reasons that vaccines, masks, and physical distancing are imperfect measures on their own to keep us safe from COVID. Each is like a slice of Swiss cheese with a couple of holes in it. When stacked together, we get an intact barrier. The immune system is so complex, this Swiss cheese model can also be applied to it. Our antibodies are imperfect. So are our memory T cells and our memory B cells. Temporary changes in one type of immune soldier does not mean the entire army collapses.

To know if COVID messes with our immune system’s ability to keep us safe, we need to zoom out of the molecular and cellular worlds and look at clinical evidence.

It’s not AIDS

If the coronavirus impairs our immune system, we expect to see more opportunistic infections in people who have recovered from COVID-19. Sure enough, trawling the literature for these reports we find a smattering of evidence showing increases in respiratory syncytial virus (RSV) in the United States, in strep throat and pink eye in Israel, and in autoimmune conditions in Germany, for example.

It is important to point out that severe viral infections do leave the body vulnerable to further infections. Our body’s barriers, which keep infectious agents out, are temporarily damaged by a particularly nasty infection. It’s easier for microbes to get in. “Because so many of us have had COVID,” Cruikshank tells me, “the probability of us then catching another thing is almost inevitable.” Especially when measures like mask mandates, remote schooling, and restrictions on indoor gatherings are lifted and we get exposed to pathogens en masse. And for those of us whom COVID put in the hospital, the consequences can be greater. Dr. Carl June, an immunologist at the University of Pennsylvania, told the New York Times in the first year of the pandemic that simply being critically ill and in the intensive care unit “can cause havoc on your immune system.” It’s called “post-intensive care syndrome,” and as Bowdish relates to me, severe respiratory infections like the flu and pneumonia that put you in the hospital can also accelerate dementia, frailty, and metabolic issues. COVID is not particularly special in this respect.

But those of us who have been vaccinated against COVID are at a much smaller risk of needing to be hospitalized when we catch the virus. Do milder infections wreck our immune system? If they routinely did, we would expect a wave of opportunistic infections like shingles, herpes, thrush, and toxoplasma. That wave has not manifested itself.

To see what true immune deficiency looks like, we can turn to AIDS. An untreated HIV infection leaves people vulnerable to microbes that the rest of us manage to keep in check. Toxoplasma, for example, is a parasite that about a third of us have been exposed to, Cruickshank tells me. “It was a big killer with AIDS, which completely destroys your helper T cells.” Measles, meanwhile, causes a sort of immune amnesia. It infects the very cells your immune system keeps around as a reminder of the bugs it has encountered, and it destroys this precious memory. “You go back to being a baby, immunologically,” Bowdish points out.

While the coronavirus is good at evading our immune system, we are simply not seeing this feared global immunodeficiency in its wake, despite all of these scary molecular and cellular changes scientists are witnessing post-COVID. That’s because these changes do not always translate to illness. With AIDS and measles, we know they do. But with cytomegalovirus or CMV, a virus that many of us have been exposed to, the story is very different. “CMV fundamentally remodels your immune system in such a dramatic way,” Bowdish mentions. “Is it associated with a risk of infectious disease? No.” A few studies seem to tie it with longevity in some Northern European countries, but essentially, CMV’s drastic immunological changes do not have consequences for our health, unless we are immunocompromised in some other way.

CMV and HIV both cause clear changes to our immune cells, but their impact on our health could not be more different. If we put them on a spectrum, with the mostly innocuous CMV being a 1 and HIV being a 10 in terms of creating a susceptibility to infection, Bowdish concludes that the data we have so far on COVID-19 places it at a 2 or 3. “Airborne HIV is….” She almost swears, contemplating the alarmist phrase that’s being tossed around to characterize COVID. “It’s not a thing as far as I’m concerned!”

While the worst possible outcome seems, for now, to have been avoided, SARS-CoV-2 does create long-term issues with the immune system of some people. Enter long COVID.

A subset of patients

It is difficult to predict what percentage of people who catch COVID will go on to develop the persisting symptoms of the still-ill-defined long COVID. The Office for National Statistics in the UK puts it at 3% based on self-reports, while a recent review of our knowledge gives a conservative estimate of 10%. The symptoms can range from a loss of smell to debilitating body-wide dysfunction. As long COVID comes into clearer focus, it appears to be an umbrella term for different conditions, caused by a persistence of the virus in the body in some, the development of antibodies that start attacking healthy tissue in others, and tiny blood clots in yet others due to viral persistence or autoantibodies. The immune system thus seemingly shares the blame for some long COVID cases. “There is quite a lot of evidence that there could well be an immune driver,” Cruikshank confirms to me, “but we absolutely need to do more to better identify these groups of patients and work out how we can better manage them and treat them. And I’m a little bit worried that often, honestly, long COVID is something that doesn’t get mentioned.”

The lack of effective medical care for long COVID patients can send them into the arms of people who capitalize on the “airborne AIDS” trope to prescribe potent drugs that target the immune system. “I’ve seen people outside of clinical trial settings,” Nirenberg reports, “give HIV antiretroviral therapy to people with long COVID off label. And those are pretty serious meds.” The repurposing of drugs to treat COVID should be adequately tested, but there are real risks when experiments are done off label with the idea that COVID causes an AIDS-like immunodeficiency.

“Airborne AIDS” vs. “COVID is just a bad cold.” This is the state of the public debate today. About the alarmist position, Nirenberg tells me, “The entire purpose of this discourse is to keep people frightened, and I think that the point is to spur policy action. I don’t really think that’s an effective strategy.” If you’re worried about immune dysfunction, Cruickshank mentions to me that the cost-of-living crisis currently happening in the UK and elsewhere can lead to malnourishment, which is bad for the immune system. “People who are starving are immunodeficient.”

And if you are worried about COVID-19—and there are valid reasons to still be concerned about this infection, chief among them cardiac complications, even in mild cases, and the possibility of lasting damage through long COVID—a clear way to reduce the risk is by being up-to-date on your COVID vaccines. Nirenberg summarizes it plainly to me: “COVID does Bad Thing X, but if you get vaccinated, Bad Thing X is substantially less likely.” Don’t forget also that the coronavirus is indeed airborne, so cleaning the air will be beneficial.

More research into the long-term consequences of an infection with SARS-CoV-2 may end up changing our understanding of how the virus affects our immune system. Based on what we know now, it is fair to say that COVID-19 can mess with the immune system, during the acute phase of a severe infection and in some of the cases of long COVID, but it is far from being an immunodeficiency bomb.

Take-home message:
- Many studies have reported changes in the molecules and cells of our immune system following a COVID-19 infection, but even dramatic changes do not necessarily imply a loss of function
- The clinical evidence we have so far does not show that a mild COVID-19 infection causes a significant immunodeficiency
- The immune system of a subset of COVID-19 patients can be impacted, particularly in cases of severe infections that require hospitalization and for some people who suffer from long COVID


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