Sleep well. Take time out to relax. Connect with your friends and family. Such things would be advisable at any time – but might it be especially important in the coming months. According to a growing body of evidence, our psychological state can shape the immune system’s reaction to a new vaccine – including the development of protective antibodies that will help us to fend off infection.
We already know that physical factors, such as the body mass index, can have an immediate effect on vaccine efficacy. In late February, for instance, a study of Italian healthcare workers found that obesity blunted the antibody response to the Pfizer/BioNTech jab. But based on our understanding of various vaccines for other diseases, it seems clear that our mental health and overall stress levels will also play an important role. “There’s quite a spectrum of opinion as to what things may help or harm the immune system,” says Prof Daniel Davis, an immunologist at the University of Manchester. “But most scientists would agree that stress has an effect.”
So what is the evidence? And how might we make use of this information? Prof Janice Kiecolt-Glaser at Ohio State University College of Medicine has pioneered much of the research. In the 1990s, she examined a group of medical students who received the hepatitis B inoculation during a particularly gruelling series of exams. The vaccine normally requires three injections, delivered over a period of seven months. But 25% of these students began to develop detectable levels of antibodies after the first dose, and their defining feature was markedly lower anxiety than the other students. Their laid-back attitude seemed to have promoted a quicker response.
To examine the consequences of stress in an older population, Kiecolt-Glaser’s team turned to a group of participants who were looking after a spouse with dementia. Round-the-clock caregiving is known to send stress levels through the roof – and Kiecolt-Glaser found that it weakened the body’s reaction to an influenza vaccine. Four weeks after receiving a shot, just 38% of the stressed carers had shown a clinically significant increase in the relevant antibodies, compared with 66% in a control group who had been matched for age and economic background. In this case, the consequences of stress were particularly pronounced in the older participants – known to have weaker immune responses in general.
Importantly, mental strain can also have long-term effects on the lingering protection of vaccines. “It not only takes longer to develop a clinically protective response to the vaccine; the chronic stress of caregiving seems to erode the antibody response,” says Annelise Madison, a clinical psychologist in Kiecolt-Glaser’s lab, who recently co-authored a paper outlining the implications of the research for the Covid-19 pandemic. “So the immunity may not last as long, and that could necessitate more frequent vaccinations to maintain immunity.” Even worse, stress also seems to impair the action of T-cells –, which form another important line of defence against disease.
The effects of stress can depend on our personal coping mechanisms. Questioning carers about their thinking patterns, Prof Suzanne Segerstrom at the University of Kentucky found that negative rumination can heighten the impact of stress on the immune system, compared with people who are able to distract themselves with more neutral topics. This finding may explain why people who score high on neuroticism tend to show impaired vaccine responses. In general, people with neurotic personalities tend to churn over their worries for long periods of time, which can amplify and prolong their reactions to relatively small stressors. This tendency seems to harm their health in numerous ways – including a significantly reduced capacity to build long-lasting protection following an influenza vaccine.
Our reaction to a vaccine may also depend on our sleep, which is often disrupted by stress. In an experiment in 2003, a group of young adults were asked to stay awake for 36 hours after receiving the hepatitis A vaccine – the equivalent of taking an all-nighter to complete an essay. One month later, their antibody count was around half that of a group who had been allowed to sleep normally on the night of the vaccination. The finding has since been replicated in many other age groups. Looking at middle-aged adults receiving the hepatitis B vaccine, a team of researchers at the University of Pittsburgh found that each additional hour of shut-eye corresponded to a 56% increase in antibody levels at follow-ups. Like chronic stress, poor sleep seems to make the immune system more “forgetful” – leading to reduced protection in the long-term.
Finally, there’s the level of social support that we receive. It is now well accepted that loneliness can be its own source of unhappiness and magnifies the impact of things like poverty. Even small, everyday challenges can feel much more overwhelming if you don’t have a network of people to help relieve your burden. Sure enough, people with smaller social networks – measured, for example, by the number of people they contact each month – appear to show weaker protection following a vaccine. For similar reasons, vaccine efficacy responses can even depend on the quality of your marriage. In one study, happier couples tended to show more effective immune responses to an influenza vaccine than those who felt they lacked an emotional connection to their spouse.
While the exact mechanisms behind these effects are still under discussion, scientists studying psychoneuroimmunology have found many ways that the mind can influence the body. Stress hormones such as cortisol are known to disrupt overall immune function, so that it fails to respond to threats in the most appropriate way. The poor sleep and depression that arise from chronic stress can also lead to low-grade inflammation throughout the body, which also seems to inhibit the production of antibodies.
We are still waiting for studies that look specifically at the new Sars-CoV-2 shots. But given the variety of the research, on many different types of vaccinations, there is every reason to think these factors will be relevant to the current immunisation programme. “You’re still engaging the same processes within the immune system, so I would expect to see similar effects,” says Prof Anna Whittaker, who studies behavioural medicine at the University of Stirling. She emphasises that the average efficacy for the Covid injections is generally very high, but stress could nevertheless reduce the optimum level of protection in certain individuals – particularly if they have other risk factors, such as old age or obesity, that will also impair their response.
Prof Danny Altmann, an immunologist at Imperial College London, agrees. He says that similar mechanisms may also play a role in the symptoms of long Covid. “People are reporting that it kind of comes and goes, and one of the things that is definitely acting as a trigger there is stress.” In this way it looks similar to diseases like multiple sclerosis, he says, which are also known to flare up during times of tension.
The million-dollar question, of course, is whether we can make use of these findings to optimise our bodies’ responses to the vaccines. So far, a handful of studies have investigated specific interventions. In one striking experiment, Prof Kavita Vedhara at the University of Nottingham offered cognitive behavioural therapy (CBT) to elderly carers looking after a spouse with dementia. The CBT took place over eight weekly sessions and included advice on the best ways to relax during stressful episodes, alongside techniques to avoid negative, ruminative thinking. Of those receiving this therapy, 50% showed a large increase in antibodies following an influenza vaccination – compared with just 7% of carers who had not attended the therapy sessions. “The magnitude of the difference between the groups was really quite surprising,” says Vedhara.
A few experiments have also examined the benefits of mindfulness, tai chi, and “expressive writing” – in which people release pent-up feelings in short essays. And the results have been promising. Unfortunately, it has been hard to raise enough funds to build a large evidence base. “The funding bodies are still catching up with the science,” says Vedhara. This makes it difficult for scientists to offer firm recommendations on the optimum ways to combat stress and boost our immune response. Davis, however, hopes that continued research during the pandemic may provide further cues for interventions in the future. “There’s going to be an enormous amount of data on how different people respond to that vaccine – and we might well come up with a much deeper understanding of how this relates to their lifestyles.”
For the time being, the researchers all agree that the potential benefits to the immune system should be an additional motivation for practising some general self-care. “I think the vaccine serves as a good wake-up call,” says Madison. “If somebody is experiencing anxiety or depression, now would be a fantastic time to seek mental healthcare.”
At the very least, we can try to prioritise sleep and exercise, and to catch up with friends and family online – any activity, in short, that will boost our wellbeing through the next few months. “That’s not going to do you any harm. And the observational evidence would suggest that it could actually improve how well these vaccines work,” says Vedhara.