October 24, 2022
2 min read
October 24, 2022
2 min read
Epstein-Barr virus replication may be a cofactor in a subgroup of patients who develop long COVID fatigue, although other potential contributing factors need to be evaluated as well, according to a letter published in Allergy.
Up to 10% of patients with COVID-19 develop long COVID, Johanna Rohrhofer, MS, PhD student with the Institute of Pathophysiology and Allergy Research, Medical University of Vienna, and colleagues wrote.
Although Epstein-Barr virus (EBV) has been associated with post-viral fatigue, the researchers said the mechanisms that lead to post-viral fatigue syndrome overall and in long COVID in particular are unresolved.
The researchers hypothesized that long COVID fatigue may be triggered by SARS-CoV-2 persistence in the gastrointestinal or respiratory tract after acute disease or by COVID-19-associated reactivation of EBV.
The study involved 30 patients (mean age, 37.73 years ± 9.96; 73.4% female) with long COVID experiencing persistent fatigue, post-exertional malaise, autonomic dysfunction and/or orthostatic intolerance.
The researchers collected stool, throat washings and blood samples from these patients between 74 and 471 days (median, 235 days) after the beginning of their acute SARS-CoV-2 infections.
The study also included 20 age-matched and sex-matched patients (mean age, 33.9 years ± 11.95; 65% female) who had fully recovered from acute SARS-CoV-2 infection as controls, with stool, throat washing and blood samples taken from them between 106 and 571 days (median, 275 days) after the beginning of their infections.
SARS-CoV-2 infections were mild in both groups and occurred between spring 2020 and autumn 2021. There were no hospitalizations for any of these patients.
The researchers did not find SARS-CoV-2 RNA in any of the throat washing or stool samples.
Also, there were no differences in SARS-CoV-2 IgA or IgG antibody titers between the cohorts. The researchers noted that 24 of the 30 patients with long COVID and 17 of 20 of the controls received COVID-19 vaccination after developing the disease but before the samples were taken.
The blood and stool samples all were negative for EBV, whereas the throat washing samples of 15 (50%) patients with long COVID and four (20%) controls were positive for EBV DNA (P = .0411). The load levels of EBV did not differ significantly between the groups.
Except for one patient in the control group, all the patients in the study had previous EBV infections. The researchers concluded that the EBV replication that they had observed was caused by EBV reactivation and not primary infection. Additionally, the groups did not have any differences in EBV-specific antibody titers.
Overall, the researchers said they did not detect any SARS-CoV-2 persistence in any of the study participants up to 10 weeks after infection, although the patients with vs. without long COVID fatigue had more EBV reactivation in their throat months after acute SARS-CoV-2 infection.
These findings indicate that cofactors in long COVID fatigue may include EBV replication, the researchers wrote, adding that they did not evaluate human leukocyte antigen subtype or other contributing factors.
The researchers acknowledged they could not confirm earlier reports of differences in EBV antibody profiles among patients with long COVID and that additional, larger studies are necessary to clarify the impact and mechanism of long COVID fatigue associated with EBV.
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.
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.”
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.”
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.
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.
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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