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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.

Dr Danuta Skowronski

“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.

Dr Marc Germain

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.

Dr Caroline Quach-Thanh

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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