Within weeks of the emergence of the COVID-19 pandemic in early 2020, it had already become something of a cliché to speak of the "unprecedented times." But while SARS-CoV-2 may have torn across a fully globalized planet in record time, almost no single element of the pandemic has been entirely unprecedented. Right now, as children in the United States are returning to school, rates of new SARS-CoV-2 infections in some states are the highest since the start of the pandemic. But this is hardly the first time the educational system has faced the threat of contagious outbreaks within school walls. One hundred years ago this month, in Sept. 1921, the country had record-breaking numbers of diphtheria cases, and schools, doctors and public health authorities were hard at work trying to determine the best ways to keep children and their communities safe from infection.

Preventing the Spread of Infection in Schools

The role of schools in the spread of COVID-19, and the prevention of its spread, has been a particularly fraught issue throughout the pandemic. In March 2020, worldwide school closures were one of the most dramatic indications of the efforts being undertaken to flatten the curve and slow the spread of SARS-CoV-2. By the summer of 2020, during the height of the second surge in the United States, school districts, families and public health experts were debating whether and how to resume in-person learning. Now, one year later, in the midst of the fourth surge, most schools are starting the school year in person, but governors in states such as Fla. and Texas are attempting to prevent mask mandates in schools despite skyrocketing numbers of cases, hospitalizations and deaths.

On Sept. 15, 1921, the editors of the Boston Medical and Surgical Journal (now the New England Journal of Medicine) opened Volume 185, Issue 11 with an editorial titled "OPENING OF THE PUBLIC SCHOOLS," which urged family doctors to cooperate with school and health boards, including school physicians. In a refrain familiar from discussions about masking, testing and quarantine policies in 2021, the editors pointed out that infectious diseases in schoolchildren have implications that extend beyond infected children themselves: "The problems concerning school children are twofold, affecting the individual child and also his associates…"

The particular infection that the editors were concerned with was diphtheria, a toxin-mediated infection caused by Corynebacterium diphtheriae, which was a leading cause of childhood deaths at the time. 1921 saw a peak in diphtheria activity in the United States: more than 200,000 cases at a time when the case-fatality ratio (deaths per cases) was 5-10%. Children infected with diphtheria often developed an extensive blue-gray pseudomembrane over their tonsils, and if the membrane grew too large, or if a chunk of it broke off and entered the airway, the child could die from asphyxiation; this effect gave the disease its ghastly nickname, "the strangling angel." (In his 1938 story "The Use of Force," the writer and pediatrician William Carlos Williams memorably describes his struggle to examine the throat of a febrile child whom he suspects of having diphtheria. Williams was practicing in his hometown of Rutherford, N.J., just a few miles from Manhattan, during the diphtheria outbreak of 1921 and could easily have been writing about this period: he attributes his suspicion that the child has diphtheria to an outbreak in her school). Myocarditis (inflammation of the heart muscle) caused by diphtheria toxin was also a major cause of death.

1921: Diphtheria Control Efforts in New York City

By the outbreak of 1921, however, there were already efforts underway to control the spread ofdiphtheria in schools. In an article published the same month in the Journal of the American Medical Association (JAMA), "DIPHTHERIA PREVENTION WORK IN THE PUBLIC SCHOOLS OF NEW YORK CITY," Dr. Abraham Zingher describes a major public health project undertaken in the preceding years in which 52,000 public school students in 44 New York City schools were tested for susceptibility to diphtheria and immunized if they were found to be non-immune. By the time this project was completed in 1922, an astonishing 90,000 children had been enrolled. Zingher and his colleague William H. Park, a charter member of the Society of American Bacteriologists (now the American Society for Microbiology) compared rates of diphtheria infection in this group with those in a control cohort of the same size consisting of children whose parents had declined participation in the study. During the winter of 1921-1922, they observed only 14 cases of diphtheria in children in the study, compared to 56 cases in children who had not been enrolled. (Zingher was to die tragically 6 years later due to a gas leak that occurred in his laboratory while he was at work on an immunization for scarlet fever.)

The techniques used to test for susceptibility and to immunize against diphtheria in this project were both relatively new in 1921. The Schick test, developed by Hungarian American pediatrician Béla Schick in 1913, involved intradermal injection of diluted diphtheria toxin in the arm. If redness and swelling developed, indicating absence of antibodies and lack of immunity to diphtheria, the test was considered positive. New York schoolchildren with positive Schick tests were subsequently immunized using the toxin-antitoxin (TAT) mixture developed around the same time by Emil Behring and studied extensively by Park. The diphtheria toxin in these mixtures stimulated production of antibodies, while the antitoxin (obtained from horse serum) reduced the risk of damage from the toxin itself.

The Schick test was important in this project because the risks of TAT, while relatively low, were too high to justify administration to children who were already immune due to natural disease and therefore would not benefit from TAT. The toxin itself could be dangerous if the mixture was not prepared properly, while the antitoxin could cause a systemic reaction to non-human proteins called serum sickness. The test was also used by Park to assess the development of immunity following immunization. Later, once inactivated diphtheria toxoid was developed, the risk of vaccination became minimal, and testing for immunity was abandoned in favor of universal vaccination beginning in the 1930s. Routine childhood vaccination with diphtheria toxoid, as a component of tetanus-diphtheria and tetanus-pertussis-diphtheria immunizations, continues to this day, and has virtually eliminated diphtheria in the United States.

2021: COVID-19 in the United States

Unfortunately, it will be a long time before the same can be said of COVID-19. In Sept. 2021, the Delta variant and stalling vaccine uptake are reversing some of the progress made against the pandemic earlier in the year by the introduction of safe, effective vaccines. Most of the measures that will be needed to bring the virus under control will not be at all unprecedented: just as testing and vaccination were cornerstones of diphtheria control a century ago, they remain key to controlling COVID-19 today. (And those vaccine passports you’ve heard about? You could get them 100 years ago too.)

When experts advise that children with symptoms that could be caused by SARS-CoV-2 infection stay home from school, there is, indeed, a precedent: "So far as the individual child is concerned," the editors of the Boston Medical and Surgical Journal wrote in Sept. 1921, "he should not be subjected to the strain of school life as long as he has a cough, abnormal temperature or any evidence of disease which can be remedied or is a source of danger to others." When experts warn of the possibility of asymptomatic transmission, there is again a precedent: "…an apparently healthy carrier [of diphtheria] may bring grave danger to groups of scholars," warned the editorial. And when doctors and public health officials advocate for implementing measures like masking and vaccination that will allow children to return safely to school during the COVID pandemic, they do so for a reason that was well understood a century ago: "Since school life is a necessary feature of civilization the public has a grave responsibility in eliminating every known danger incident thereto."

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