Summary: Those with pre-existing anxiety, depression, chronic stress, and distress caused by loneliness are at 50% increased risk of developing Long-COVID following coronavirus infection.
Source: The Conversation
Stress is part and parcel of modern life. When we’re on the verge of a new challenge or a significant event, we can experience stress mixed with excitement and a sense of challenge. This form of “good” stress, or eustress, is important for growth, development, and achievement.
However, prolonged stress and overwhelming or traumatic events can negatively impact our health. These forms of “bad” stress – or distress – can make us sick, depressed, anxious and over the long term, increase our risk of heart disease, stroke, type 2 diabetes, dementia and even cancer.
Distress can also affect our ability to fully recover from COVID. Ongoing symptoms for a month or more is referred to as long COVID. Those affected can experience fatigue, brain fog, shortness of breath, loss of taste and smell, difficulty sleeping, anxiety and/or depression. For some, these symptoms can last for many months or even years, making it impossible to return to pre-COVID life.
In a Harvard University study published last month, people suffering psychological distress in the lead up to their COVID infection had a greater chance of experiencing long COVID. The researchers found those with two types of distress (depression, probable anxiety, perceived stress, worry about COVID, and loneliness) had an almost 50% greater risk of long COVID than other participants.
So how might distress impact the body’s ability to fight infection?
First, we need to look at inflammation
Inflammation is the body’s way of responding to an infection or injury.
When the immune system encounters a virus, for example, it launches an attack to neutralise infected cells and store a memory of that virus so it can respond faster and more effectively the next time.
Many things can cause inflammation, including bacteria and viruses, injuries, toxins and chronic stress.
The body has many different responses to inflammation, including redness, heat, swelling and pain. Some inflammatory responses can occur silently within the body, without any of these typical symptoms. At other times, inflammation can mobilise energy resources to cause exhaustion and fever.
During inflammation, immune cells release substances known as inflammatory mediators. These chemical messengers cause small blood vessels to become wider (dilate), allowing more blood to reach injured or infected tissue to help with the healing process.
This process can also irritate nerves and cause pain signals to be sent to the brain.
What does distress have to do with inflammation?
In the short term, stress causes the release of hormones that suppress inflammation, ensuring the body has enough energy resources available to respond an immediate threat.
However, when experienced over an extended period of time, stress itself can cause low grade “silent” inflammation. Chronic distress and related mental health conditions such as anxiety and depression, are all associated with elevated levels of inflammatory mediators. In fact, the repeated exposure to mild, unpredictable stress is enough to elicit an inflammatory response.
Pre-clinical (lab-based) studies have shown chronic mild stress can cause depression-like behaviour by promoting inflammation, including activating immune cells in the brain (microglia). When anti-inflammatories were given during the mild stress exposure they prevented depression-like behaviour. However if given after the event, the anti-inflammatories were ineffective.
When inflammation is ongoing, such as with extended periods of distress, the immune system changes the way it responds by reprogramming the immune cells. Effectively, it switches to “low surveillance mode”. In this way, it remains active throughout the body, but downgrades its responsiveness to new threats.
Because of this, the response may be slower and less effective. Consequently, the process of recovery can take longer. For a virus like COVID, it’s possible that prior exposure to distress may similarly impair the body’s ability to fight the infection and increase the risk of long COVID.
How might distress affect recovery from COVID?
There is still much to learn about how COVID infection affects the body and how psychological factors can impact clinical outcomes in the short and long term.
COVID has far-reaching effects across multiple body systems, affecting the lungs and heart to the greatest degree, and increasing the risk of blood clotting and stroke.
Because the virus resides within human cells, an immune system switched to “low surveillance mode” as a result of psychological distress may miss early opportunities to destroy infected tissues. The virus can then gain an advantage over the defence (immune) system.
Conversely, distress can suppress the early response, tipping the balance in favour of the invader.
So what can we do about it?
Vaccines work by helping to train the immune system to find the target sooner, giving the immune system the advantage.
Behavioural interventions that improve the ability to cope with stress decrease inflammation and may help to enhance the immune response to COVID.
It’s also important to be aware that exposure to COVID increases the risk of depression, anxiety or other mental health conditions. Knowledge of this two-directional link is the first critical step to improving clinical outcomes.
A lifestyle medicine approach that helps to reduce levels of distress and address mental health symptoms has important downstream benefits for physical health. This is likely to not only be the result of direct effects on the immune system itself, but also through related improvements in health behaviours such as diet, exercise and/or sleep.
Further research is needed to better understand the impact of distress on the immune system, mental health and COVID outcomes, and to highlight ways to intervene to prevent long COVID and support recovery.
About this stress and Long-COVID research news
Breakthrough Infections More Likely in Infliximab Treated IBD Patients Than Those Treated With Vedolizumab
Patients with inflammatory bowel disease (IBD) treated with infliximab who were vaccinated against SARS-CoV-2 were more likely to have a breakthrough infection than patients treated with vedolizumab, but the benefits of the vaccine are still superior.
A team, led by Zhigang Liu, PhD, Department of Metabolism, Digestion and Reproduction, Imperial College London, determined how infliximab and vedolizumab affect vaccine-induced neutralizing antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants.
Anti-TNF drugs, including infliximab, are linked to attenuated antibody responses following SARS-CoV-2 vaccination. The variants included in the analysis have the ability to evade host immunity and with emerging sublineages are currently the dominating variants causing the current waves of infection.
In the prospective, multicenter, observation, CLARITY IBD cohort study, the investigators looked at the effect of infliximab and vedolizumab on SARS-CoV-2 infections and vaccinations in patients with IBD.
The study included patients aged 5 years or older with an IBD diagnosis that were treated with infliximab or vedolizumab for 6 weeks or longer in infusion units at 92 hospitals in the UK. Each participant had uninterrupted biological therapy since recruitment and were not previously diagnosed with a SARS-CoV-2 infection.
The investigators sought primary outcomes of neutralizing antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 following 3 doses of a SARS-CoV-2 vaccine.
The team also investigated the risk of breakthrough infections in relation to neutralizing antibody titers using Cox proportional hazard models.
There were 7224 patients with IBD recruited to the study between September 22 and December 23, 2020. Of this group, 1288 had no previous SARS-CoV-2 infections after 3 doses of the vaccine that were established on either infliximab (n = 871) or vedolizumab (n = 417). The median age of the patient population was 46.1 years.
Following 3 doses of SARS-CoV-2 vaccine, 50% neutralizing titers were significantly lower in the infliximab group compared to patients treated with vedolizumab against wild-type (geometric mean, 2062; 95% CI, 1720–2473 vs geometric mean, 3440; 95% CI, 2939–4026; P <0.0001), BA.1 (geographic mean, 107.3; 95% CI, 86.40–133.2 vs geographic mean, 648.9; 95% CI, 523.5–804.5; P <0.0001), and BA.4/5 (geographic mean, 40.63; 95% CI, 31.99–51.60] vs geographic mean, 223.0; 95% CI, 183.1–271.4; P <0.0001) variants.
Breakthrough infections more frequently occurred in patients treated with infliximab (n = 119; 13.7%; 95% CI, 11.5–16.2) than in those treated with vedolizumab (n = 29; 7.0%; 95% CI, 4.8–10.0; P = 0.00040).
The Cox proportional hazard models show time to breakthrough infection after the third vaccine dose in the infliximab group was associated with a higher hazard risk than treatment with vedolizumab (HR, 1.71; 95% CI, 1.08-2.71; P = 0.022).
There was also higher neutralizing antibody titers against BA.4/5 with a lower hazard risk in the group with a breakthrough infection and a longer time to breakthrough infection (HR, 0.87; 95% CI, 0.79-0.95; P = 0.0028).
“Our findings underline the importance of continued SARS-CoV-2 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies,” the authors wrote.
The study, “Neutralizing antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicenter cohort study,” was published online in The Lancet Gastroenterology & Hepatology.
Flu shot uptake in children ‘too low,’ P.E.I. CPHO says
With flu cases on the rise in the province, P.E.I.’s Chief Public Health Officer is urging parents to get their young children a flu shot.
Currently, just 19 per cent of children under the age of 10 have gotten a vaccine.
“I do think that’s too low,” said Dr. Heather Morrison, the province’s chief public health officer. “On the other hand, we’ve had great uptake of our high dose influenza for those who are 65 years of age and up.”
Morrison said there are some clinics on the weekend in Charlottetown through public health nursing and appointments are available “to really help those who may not be able to come during the week.”
By Dec. 3 there have been 155 lab-confirmed cases, according to a P.E.I. government website. The median age of cases to date is 14 years old. The site says there was “widespread flu activity” last week on P.E.I. with flu activity “above expected levels for this time of year.”
‘They are getting better now’
Without vaccines, children four and under are most at risk of being hospitalized, Morrison said. That’s exactly what happened to Island resident Shidhin Philip’s youngest son, Adam, who was less than a month old when he was hospitalized with influenza and RSV.
“We were really scared,” said Philip. “But we know we took him to the hospital at the right time, so that was a good decision.”
On Wednesday, Philip brought two of his older children to the children’s clinic in Sherwood to get their flu shot.
“They all had the flu, the sore throat, running nose, they had fever, they were throwing up. They were absent from school for two weeks,” Philip said. “They are getting better now, I don’t want to get it back again. So I took the appointment for the flu shot today.”
But he says having vaccines available at public schools would make it easier for busy parents to get their children vaccinated.
“They can send the paper home, we can sign the consent,” he said. “Instead of making an appointment or waiting [a] long time, you know, it can finish in one day.”
Morrison says there are some logistical issues with making the vaccine available in schools, but it is something the province is potentially looking into for future years.
“It’s something that we certainly would be very open to having that conversation with education, public health, nursing, Health P.E.I,” she said. “It has been something that has been discussed over the years.”
In the meantime, she encourages parents to make an appointment and hopes strong messaging, combined with the recent spike in flu cases, will motivate parents to book their kids’ shots.
“Children are at school, and activities, we’re all busy,” she said. “But if we can get it now, get our children vaccinated, ourselves vaccinated, it will protect us in time for the holidays.”
SARS-CoV-2 Seroprevalence Grew Rapidly in Canada
Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
By August 2022, 2½ years into the COVID-19 pandemic, most children and adults younger than 60 years had been vaccinated against SARS-CoV-2 or showed evidence of having been infected by the virus, new data suggest.
A Canadian seroprevalence study of almost 14,000 people found that fewer than 50% of people older than 60 years (the age group that is most vulnerable to severe outcomes) showed evidence of immunity from infection or had been vaccinated by August 2022. Older adults, who have the lowest infection rates but are at highest risk of severe outcomes, should continued to be prioritized for vaccination, according to the authors.
The data were published online December 5 in the Canadian Medical Association Journal.
Children Most Affected
Previous evidence suggests that a combination of infection and vaccination exposure may induce more robust and durable hybrid immunity than either infection or vaccination alone, study author Danuta Skowronski, MD, MHSc, an epidemiologist at the British Columbia Centre for Disease Control in Vancouver, told Medscape Medical News.
“Our main objective was to chronicle the changing proportion of the population considered immunologically naive and therefore susceptible to SARS-CoV-2,” she added. “It’s relevant for risk assessment to know what proportion has acquired some priming for more efficient immune memory response to the virus, because that reduces the likelihood of severe outcomes.” Standardized seroprevalence studies are essential for informing COVID-19 response, particularly in resource-limited regions.
The investigators analyzed anonymized residual sera from children and adults in an outpatient laboratory network in British Columbia’s Greater Vancouver and Fraser Valley region. They used at least three immunoassays per serosurvey to detect antibodies to SARS-CoV-2 spike (from vaccine) and to nucleocapsid antibodies (from infection).
The researchers determined any seroprevalence (vaccine-induced, infection-induced, or both) on the basis of a positive finding on any two assays. Infection-induced seroprevalence was also defined by dual-assay positivity but required both antinucleocapsid and antispike detection. Their estimates of infection-induced seroprevalence indicated considerable underascertainment of infections by standard case-based surveillance reports.
During the first year of the pandemic, when public health measures to curtail viral transmission were in place, the study population’s seroprevalence rate was less than 1% for the first three measurements. It was less than 5% by January 2021. With age-based vaccine rollouts, however, seroprevalence increased dramatically during the first half of 2021 to 56.2% by May–June 2021 and to 83% by September–October 2021. More than 85% of the population remained uninfected.
Infection-induced seroprevalence was less than 15% in September–October 2021 until the arrival of the Omicron waves, after which it rose to 42.5% by March 2022 and 61.1% by July–August 2022. Combined seroprevalence from vaccination or infection was more than 95% by the summer, with most children, but fewer than half of adults older than 60 years, showing evidence of having been infected.
“We found the highest infection rates among children, closely followed by young adults, which may reflect their greater interconnectedness, including between siblings and parents in the household, as well as with peers in schools and the community,” the authors write. They note that the low cumulative infection rates among older adults may reflect their higher vaccination rates and greater social isolation.
US data show similar age-related infection rates, but data among children from other Canadian provinces are limited, the authors write.
Broadly Applicable Findings
Commenting on the study for Medscape, Marc Germain, MD, PhD, vice president of medical affairs and innovation at Héma-Québec in Quebec City, said that the pattern observed in British Columbia is representative of what happened across Canada and the United States, including the sweeping effect of the Omicron variant and the differences in impact according to age. “But regional differences might very well exist — for example, due to differential vaccine uptake — and are also probably related in part to the different testing platforms being used,” he said. Germain was not involved in the study.
Caroline Quach-Thanh, MD, PhD, a pediatrician and epidemiologist-infectologist at the University of Montreal, pointed out that in Quebec, seroprevalence surveys that were based on residual blood samples from children and adults who visited emergency departments for any reason showed higher rates of prior infection than the British Columbia surveys. “But Dr Skowronski’s findings are likely applicable to settings where some nonpharmacological interventions were put in place, but without strict confinement — and thus are likely applicable to most settings in the US and Canada.” Quach-Thanh was not involved in the study.
She added that the use of residual blood samples always entails a risk for bias, “but the fact that the study method was stable should have captured a similar population from time to time. It would be unlikely to result in a major overestimation in the proportion of individuals positive for SARS-CoV-2 antibodies.”
A recent global meta-analysis found that while global seroprevalence rates have risen considerably, albeit variably by region, more than a third of the world’s population is still seronegative to the SARS-CoV-2 virus.
The Public Health Agency of Canada and the Michael Smith Foundation for Health Research provided funding for the study. Skowronski has received institutional grants from the Canadian Institutes of Health Research and the British Columbia Centre for Disease Control Foundation for Public Health for other SARS – CoV-2 work. Germain and Quach-Thanh have disclosed no relevant financial relationships.
CMAJ. Published online December 4, 2022. Full text
Diana Swift is a freelance medical journalist based in Toronto.
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