A history of diphtheria and tetanus vaccination may partly explain why some people with COVID-19 do not require hospitalization. David Greedy/Getty Images
- Tetanus and diphtheria vaccines may produce protective effects against COVID-19.
- Preliminary data finds severe disease outcomes significantly reduced among people who have received vaccines.
- Scientists say that the vaccines could be achieving this by priming the innate immune response to fight.
The way that COVID-19, the infectious respiratory disease caused by the SARS-CoV-2 virus, progresses is different for everyone.
Although some people experience no or only mild flu-like symptoms and emerge unscathed from the infection, some require hospitalization and intubation due to respiratory failure and varying levels of organ support. For other people, it is fatal.
Termed “interindividual variation,” health experts have largely attributed these differences in disease progression and outcome to differences in immune function.
Older adults, men, those with preexisting chronic health conditions, and people from minoritized communities are more likely to have severe COVID-19 and die.
When it comes to matters of immunity, however, there is another factor that comes into play: vaccination history.
Vaccines are key elements that train the immune system to fight a variety of pathogens that cause people to fall ill. They also stimulate the “innate” immune response, which is the body’s first line of defense against invaders.
This is the part that has spurred scientists to investigate whether or not previous vaccinations can provide protection against other diseases, including COVID-19.
Old tricks for new challenges
The notion that old vaccines might help in the fight against COVID-19 has persisted in the scientific community since the early days of the pandemic.
So far, live attenuated vaccines — such as the measles, mumps, and rubella (MMR) vaccine and the bacillus Calmette-Guérin (BCG) vaccine against tuberculosis — have dominated research and discussions on the matter.
For BCG, for example, some research has suggested that the vaccine can “enhance the innate immune response to subsequent infections” and reduce respiratory tract infections.
Newer studies, however, have looked into inactivated vaccines — particularly diphtheria, tetanus, and pertussis (DTP) vaccines — to see if previous inoculations translate into less severe manifestations of COVID-19.
A 2020 study investigated the bacterial vaccines DTP and meningitis B and deduced that children’s likely protection against SARS-CoV-2 could be down to cross-reactivity prompted by these vaccinations.
Cross-reactivity is an important mechanism for heterologous immunity, which happens when one pathogen induces an immune response to an unrelated pathogen in the future.
Because immunity wanes over time, especially when people do not receive booster shots, the researchers concluded that this could explain why older adults have more susceptibility to COVID-19.
Despite diphtheria, tetanus, and pertussis is caused by bacteria and COVID-19 by a virus, multiple studies have demonstrated heterologous immunity.
A 2021 study in the journal Medical Hypotheses suggested that with the aid of artificial intelligence, tetanus vaccination may be contributing to the reduced severity of COVID-19.
In line with that hypothesis, a recent study — which has not yet undergone peer review — added to existing research and suggested that older adults who have received diphtheria or tetanus vaccine booster within the past 10 years may have a lower risk of severe COVID-19.
The researchers chose the 10-year timeframe to account for the waning of vaccine-induced antibodies over time. It is also the interval during which experts recommend booster shots.
The findings
As part of the study, the researchers analyzed the immunization records and COVID-19 testing data of 103,049 participants, with an average age of 71.5 years, using the UK Biobank cohort.
The researchers took into account age, sex, underlying respiratory diseases, and socioeconomic status.
Participants who had received any of the DTP vaccinations during the past 10 years were, on average, younger and had a higher socioeconomic status than those who had not been vaccinated against these diseases within the same timeframe.
It is important to note that having a lower socioeconomic status, along with a wide range of social determinants of health that contribute to health inequity, may be linked with a higher risk of COVID-19 and worse outcomes, according to previous research.
The results of the UK Biobank analysis showed that those who had received either tetanus or diphtheria booster were less likely to receive a positive SARS-CoV-2 test. However, more importantly, the researchers found a statistically significant link between the boosters and the likelihood of having severe COVID-19.
Those who had received a tetanus booster were half as likely to develop severe COVID-19, and those who had received a diphtheria booster were 54% less likely.
The researchers found “no significant differences in the likelihood to test positive or [have] a severe case” with the pertussis vaccine, and they noted the small sample size.
The report is available on the medical website medRxiv ahead of peer review.
Odds of receiving a booster
In most countries around the world, people receive vaccinations against tetanus in childhood, along with diphtheria and pertussis or polio. Some countries employ lifelong immunization programs to repeat booster shots every 10 years, while for other countries, health experts only recommend top-ups when traveling abroad or after injury.
In the United States, the Centers for Disease Control and Prevention (CDC) continue to recommend booster vaccines every 10 years after 18 years of age. However, these are not mandatory.
Officials also recommend regular boosters for tetanus, diphtheria, and, in some cases, pertussis in many European countries, especially for older adults. However, in the United Kingdom, because nationwide and routine immunization against tetanus only began in 1961, those born before that date do not carry protective antibodies for tetanus nor diphtheria.
According to World Health Organization (WHO) data from 2019, African countries such as Congo, Cameroon, Angola, and Ethiopia — where dropout rates for immunization are considerably high for vaccines that need repeating — only around 60% or less of the population receive their third tetanus booster shots later in life.
In South America, particularly in countries such as Haiti, booster coverage falls under 80%.
Bar Iraq and Syria, DTP booster rates remain above 70% for most countries in the Eastern Mediterranean and the Middle East.
Vaccination coverage also varies around Southeast Asia, with most achieving above 70% coverage for the third booster of the DTP vaccine. In addition, for matters of tourism, the National Travel Health Network and Centre of Vietnam and the WHO still recommend that backpackers and travelers receive a tetanus shot before their visit.
The bottom line
The immune system employs a complex set of protective mechanisms against various pathogens. When it comes to immunity to SARS-CoV-2, preexisting immunological memory to other viruses or bacteria may well give it a head start.
However, the authors of the study do acknowledge that their data cannot establish a causal link between vaccine boosters, in particular diphtheria and tetanus, and the severity of COVID-19 but instead suggest a strong correlation.
They attribute the effect of the booster shots to a degree of protection against severe symptoms by way of stimulating the immune system. The authors write:
However, “the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations,” the authors conclude.
Speaking to Medical News Today, David Cutler, a family medicine physician at Providence Saint John’s Health Center in Santa Monica, CA, said that the data were not surprising considering previous evidence that unrelated vaccines, such as the measles, combined MMR, and BCG vaccines, could provide protection against COVID-19.
“But it does raise more questions than it answers. … There are areas of uncertainty that could not be addressed [in the study]. Were all vaccines accounted for? Were other social factors which led to people getting vaccinated responsible for the more favorable COVID-19 outcomes? What is the nature of the immunity which may have produced better outcomes?”
Cutler noted that the notion that routine vaccines provided benefits against COVID-19 was nonetheless intriguing.
“The clinical implication is that the benefits of vaccines may be even greater than previously realized. This is a potent reminder to receive not only a COVID-19 vaccine as soon as possible, but other routine vaccines when they are due.”
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