As a doctor, I thought my student loans were the worst debt I would encounter. But the past two months I’ve spent at work in a pediatric hospital in Baltimore have made paying them off seem like child’s play. Pediatricians like me are currently overwhelmed amid a resurgence of respiratory viruses. Infants and toddlers, unable to catch their breath from pneumonia or bronchiolitis (an infection of the small airways in the lung), are filling America’s pediatric emergency departments, hospital beds, and intensive care units. Where I work, sick kids have filled our waiting rooms, then filled our makeshift second waiting rooms, and finally filled the emergency medical tents we erected outside. While RSV and influenza have been the predominant viruses, numerous co-conspirators—parainfluenza, human metapneumovirus, rhinovirus, enterovirus, and COVID-19—are also causing havoc.
So why are kids getting sick with every virus everywhere, all at once? Most experts have converged upon an answer: We are paying back a collective “immunity debt,” one accrued from the quiescence of traditional respiratory viruses during the COVID-19 pandemic.
The prevalence of these infections plummeted due to the nonpharmaceutical interventions, or NPIs (things like masking, remote work and learning, enhanced hygiene, and isolation of those who are ill), that were put in place to slow SARS-CoV-2 but had profound effects on other viruses, essentially halting their spread around the world. Fewer recent infections led to less immunity, which meant more—and more severe—infections once viruses staged their comeback. Sprinkle in the return of cold weather and a widespread reversion to pre-pandemic living, and voilà: The usual winter wave of viruses has become a tsunami.
As to why so many newborns are falling ill, it’s likely they inherited their debt from mom. Like kids, fewer moms were sick the past two years with non-COVID-19 respiratory pathogens, which means fewer babies received protective antibodies through the placenta and from breast milk. (To be clear, this does not mean that a pregnant person should go out and get infected in order to confer their child antibodies. Getting infected in order to stave off future infection is always a losing strategy.)
Immunity debt is not a new idea, though the specific coinage is fairly recent (and some experts bicker over the specifics of what the phrase does and does not mean). Its painful lesson has been learned by American honeymooners who drink the tap water in Cancún, Nigerian Americans who skip malaria prophylaxis while visiting their cousins outside Abuja, and unvaccinated seniors who were hospitalized from COVID-19 while their boosted peers suffered a mere head cold. At its heart, immunity debt is Immunology 101: Hosts whose immune systems haven’t been properly primed are more prone to infection and severe disease.
Select skeptics have questioned whether immunity debt, at least by itself, explains what we’re seeing. Researchers at Nationwide Children’s Hospital are investigating whether a new strain of respiratory syncytial virus, or RSV, which began circulating the summer before the pandemic, may be partially to blame. It could be, though it wouldn’t explain the rise we are seeing in other respiratory viruses as well.
Other experts have speculated that prior COVID-19 infections are causing immune suppression, and that this is to blame for the current viral resurgence. While such a phenomenon is known to occur following measles infections, the data for COVID-19 infection doing the same damage is unconvincing. A study conducted by the National Institutes of Health, which compared individuals recovered from COVID-19 with noninfected controls, found no significant long-term differences in immune function. Some researchers have found detectable immune system changes in patients with long COVID, but not all immune system changes in the lab lead to a greater susceptibility to infection in the real world. In fact, in the short term, the immune response to COVID-19 actually seems to make it less likely the host will be infected with a second virus, through a phenomenon known as viral interference. Then there are epidemiologic observations: Abnormal RSV outbreaks also occurred in China, New Zealand, and Australia after COVID-19 precautions were lifted. These countries all had low COVID-19 transmission at the time, suggesting that even if they play a role, COVID-19 infections aren’t the main culprits behind the current deluge of other infections.
If our pediatric EDs and ICUs are indeed being overrun due to immune debt caused by COVID-19 precautions, does that mean their implementation was unwise in the first place? Or that we should abandon them going forward? Or should we instead double down on the precautions in an attempt to keep respiratory viruses away for good?
While fewer viral infections are good, so is hugging grandma, in-person school, and play dates with friends. Permanently suppressing respiratory viruses is nothing like eliminating foodborne illness, diarrheal disease, or malaria. Pasteurization, sewage systems, water purification, and mosquito control require minimal behavior change and have mostly positive side effects easing uptake, whereas masks are uncomfortable, social distancing is a drag, and wanderlust is widespread. Hope remains for lasting improvements in ventilation, sick-leave policies and culture, and hand hygiene, but it is clear the suite of interventions which were required for sustained community suppression of respiratory viruses has proved both prohibitively painful and politically unpalatable. Respiratory viruses are here to stay.
But we can be more clever in living with these microbes. While RSV and influenza slumbered these past few years, society was learning an unprecedented amount about their behavior and the effect public health actions have on them. This knowledge allows us to employ nonpharmaceutical interventions more strategically going forward. Some interventions, such as improved ventilation, might sustainably reduce the total number of infections. Other strategies, like masking, travel restrictions, and social distancing, are, as we’ve seen firsthand, unlikely to last. Using interventions in this second category therefore accrues immunity debt (during a period of wide uptake), which will be painfully paid off with widespread surges (when these measures are inevitably dropped).
Notably, this debt may be worthwhile when the benefit of temporarily avoiding infection is worth the risk of future disease and the annoyance of NPIs. For example, when health care systems are becoming overwhelmed, using NPIs to “flatten the curve” and allow provision of proper care is prudent. Indeed, without such interventions early on in the pandemic, health systems would have completely collapsed, costing countless lives. Amid the current upswing in pediatric illness, it makes sense to temporarily re-implement precautions such as masking, surface disinfection, and frequent hand hygiene, especially around infants and young children.
Another time taking on immune debt makes sense is when an individual (or a close contact) is facing a transient period of severe disease risk. In pediatrics, the main application is protecting newborns during the first months of life, when children are uniquely vulnerable. For babies with underlying risk factors for severe disease from respiratory viruses—prematurity, lung disease, congenital heart disease, or complex medical conditions—it’s wise to play it safe for a little longer, especially during their first fall and winter. Sure, shielded children will be more susceptible that second cold and flu season compared with their previously infected peers, but giving their immune system and lungs an extra year to mature means their risk overall has decreased. Similar logic applies to other groups temporarily facing increased risk, such as cancer patients receiving chemotherapy, anyone who is about to have an important surgery, and those whose booster is right around the corner.
Vaccines are ultimately the safest way to live with infectious organisms. Some critics have alleged that the entire concept of immunity debt is anti-vaccine, suggesting that the term insinuates that infections are the only way to prevent immunity debt. Nonsense. The infectious disease experts who coined the phrase used it to argue vociferously for the importance of inoculation. Vaccines are immunology’s free lunch. They can prevent us from going into debt by keeping the immune system primed, without the risks that come from the disease itself. Staying up to date on COVID-19 and flu shots can help prevent infections and severe disease from the viruses. (Notably, this year’s flu vaccine matches circulating strains of the virus well, according to preliminary data from the Centers for Disease Control and Prevention.) Remaining on track with—or catching up to—standard childhood vaccines adds yet another layer of protection by decreasing the risk of common complications of viral illnesses like bacterial pneumonias and ear infections, which are (predictably) also surging. Select high-risk infants are eligible for monthly preventive injections, a tactic known as passive immunization, to decrease their risk of RSV. A vaccine against RSV appears to even be around the corner. Multiple promising candidates have recently been shown to work in clinical trials.
Paying back debt is painful, especially when it’s children who are being made to suffer. But we can’t fight back if we deny the problem by smearing anyone who acknowledges immunity debt as anti-vax or anti-mask. Temporarily employing masks and increased hand and surface hygiene to bend the curve and protect those most vulnerable is reasonable while RSV and flu are surging, but the current pediatric crisis neither implies that eternal masking is needed nor that it was useless before. The tincture of time will primarily heal this problem. Pediatric infections are likely to diminish in the next year or two, as our immunity debt shrinks. New vaccine technologies on the horizon will likely add additional relief. Our collective efforts to stem the tide of the pandemic saved countless lives; it was ultimately good debt.
