During the Covid-19 pandemic, the world is unwittingly conducting what amounts to the largest immunological experiment in history on our own children. We have been keeping children inside, relentlessly sanitizing their living spaces and their hands and largely isolating them. In doing so, we have prevented large numbers of them from becoming infected or transmitting the virus. But in the course of social distancing to mitigate the spread, we may also be unintentionally inhibiting the proper development of children’s immune systems.
Most children are born with a functioning immune system with the capacity to respond to diverse types of foreign substances, called antigens, encountered through exposure to microorganisms, food and the environment. The eradication of harmful pathogens, establishment of protective immunity and proper immune regulation depends on the immune cells known as T lymphocytes. With each new infection, pathogen-specific T cells multiply and orchestrate the clearance of the infectious organism from the body, after which some persist as memory T cells with enhanced immune functions.
Over time, children develop increasing numbers and types of memory T cells, which remain throughout the body as a record of past exposures and stand ready to provide lifelong protection. For other antigen exposures that are not infectious or dangerous, a type of healthy stalemate can result, called immune tolerance. Immunological memory and tolerance learned during childhood serves as the basis for immunity and health throughout adulthood.
Memory T cells begin to form during the first years of life and accumulate during childhood. However, for memory T cells to become functionally mature, multiple exposures may be necessary, particularly for cells residing in tissues such as the lung and intestines, where we encounter numerous pathogens. These exposures typically and naturally occur during the everyday experiences of childhood — such as interactions with friends, teachers, trips to the playground, sports — all of which have been curtailed or shut down entirely during efforts to mitigate viral spread. As a result, we are altering the frequency, breadth and degree of exposures that are crucial for immune memory development.
While the immune system is influenced by multiple factors, including genetics and everyday exposures to family members and pets, the long term effects of removing the social system that brings children in contact with other people, places and things remains uncharted territory. However, there is now substantial evidence that antigen exposure during the formative period of childhood is important not only for protection but also for reducing the incidence of allergies, asthma and inflammatory diseases. A well-known theory, called the “hygiene hypothesis,” proposes that the increased incidence of allergies and other immune disorders involving inappropriate immune reactions across industrialized societies is a result of the move away from agrarian society toward a highly sanitized urban setting.
Failing to train our immune systems properly can have serious consequences. When laboratory mice raised in nearly sterile conditions were housed together in the same cage with pet mice raised in standard conditions, some of the laboratory mice succumbed to pathogens that the pet mice were able to fight off. Additional studies of the microbiome — the bacteria that normally inhabit our intestines and other sites — have shown that mice raised in germ-free conditions or in the presence of antibiotics had reduced and altered immune responses to many types of pathogens. These studies suggest that for establishing a healthy immune system, the more diverse and frequent the encounters with antigens, the better.
Clinical trials have already demonstrated the effect of antigen exposure or avoidance in early childhood on subsequent immune responses. Introduction of peanuts to infants resulted in reduced incidence of peanut allergy, while avoidance had the opposite effect of promoting unwanted, severe allergic immune responses to peanuts. These findings further suggest that exposure during the formative years is critical for developing an immune system that responds appropriately to pathogens while tolerating harmless antigens.
What can be done to promote children’s health during this relentless pandemic? To allow them to be exposed to people and the environment, while not putting their teachers, family members or caregivers at risk? Embracing proven measures such as mask wearing to control viral spread will alleviate the need for further restrictions and have disproportionate benefits for our children. It is heartening that the ongoing SARS-CoV-2 vaccine trials show great promise. The sooner that teachers and caregivers can be vaccinated, the sooner children can return to school and re-establish their normal routines.
That’s because the longer we need to socially distance our children in the midst of uncontrolled viral spread, the greater the possibility that their immune systems will miss learning important immunological lessons (what’s harmful, what’s not) that we usually acquire during childhood.
There is already well-justified concern about the impact of prolonged virtual learning on social and intellectual development, especially for elementary and middle-school-age children. The sooner we can safely restore the normal experiences of childhood, interacting with other children and — paradoxically — with pathogens and diverse microorganisms, the better we can ensure their ability to thrive as adults in this changing world.
Donna L. Farber is a professor of immunology and surgery at Columbia University Vagelos College of Physicians and Surgeons, where Thomas Connors is an assistant professor of pediatrics.
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