From the Journals

SARS-CoV-2 seroprevalence grew rapidly in pandemic’s early waves



By August 2022, two-and-a-half years into the COVID-19 pandemic, most children as well as most adults under age 60 years had evidence of SARS-CoV-2 vaccination and/or infection, a Canadian seroprevalence study of almost 14,000 people over the first seven waves of the pandemic reports.

However, fewer than 50% people older than age 60, the age group most vulnerable to severe outcomes, showed evidence of immunity from infection or vaccination. The authors noted that older adults – who have the lowest infection rates but highest risk of severe outcomes – continue to warrant prioritized vaccination, writing online in the Canadian Medical Association Journal.

Dr. Danuta Skowronski

Previous evidence suggests that a combination of both infection and vaccination exposure may induce more robust and durable hybrid immunity than either exposure alone, according to lead author Danuta M. Skowronski, MD, MHSc, an epidemiologist at the British Columbia Centre for Disease Control in Vancouver.

“Our main objective was to chronicle the changing proportion of the population considered immunologically naive and therefore susceptible to SARS-CoV-2,” Dr. Skowronski said in an interview. “It’s relevant for risk assessment to know what proportion have 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 to inform COVID-19 response, particularly in resource-limited regions.

The study

Conducted in British Columbia’s Greater Vancouver and Fraser Valley, the analysis found that in the first year of the pandemic, when extraordinary measures were in place to curtail transmission, virtually everyone remained immunologically naive. Thereafter, however, age-based vaccine rollouts dramatically changed the immuno-epidemiological landscape so that by September 2021, more than 80% of the study population had antibody evidence of immunological priming, while more than 85% remained uninfected.

By August 2022, after the Omicron-variant waves, overall vaccine- and infection-induced seroprevalence exceeded 95%, with 60% having been actually infected, including at least three-quarters of children. Fewer than 50% of older adults, however, showed immunological evidence of exposure.

The study results were based on anonymized residual sera from children and adults in an outpatient laboratory network. At least three immunoassays per serosurvey were used to detect antibodies to SARS-CoV-2 spike (from vaccine) and to nucleocapsid antibodies (from infection).

The researchers assessed any seroprevalence – vaccine-, infection-induced, or both – as defined by positivity 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 under-ascertainment of infections by standard surveillance case reports.


During the first year of the pandemic, fewer than 1% manifested seroprevalence during the first three snapshots and fewer than 5% by January 2021. With vaccine rollout, however, seroprevalence increased dramatically during the first half of 2021 to 56% by May/June 2021 and to 83% by September/October 2021.

In addition, infection-induced seroprevalence was low at less than 15% in September/October 2021 until the arrival of the Omicron waves, after which it rose to 42% by March 2022 and 61% by July/August 2022. Combined seroprevalence for vaccination or infection was more than 95% by the summer, with most children but less 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 wrote, adding that the low cumulative infection rates among older adults may reflect their higher vaccination rates and greater social isolation.

U.S. data show similar age-related infection rates, but data among children from other Canadian provinces are limited, the authors said.

Commenting on the survey but not involved in it, infectious diseases expert Marc Germain, MD, PhD, a vice president at Héma-Québec in Quebec City, believes the pattern observed in British Columbia is fairly representative of what happened across Canada and the United States, including the sweeping effect of the Omicron variant and the differential impact according to age.

Marc Germain, MD, PhD, a vice-president at Héma-Québec in Quebec City

Dr. Marc Germain

“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,” Dr. Germain told this news organization.

Caroline Quach-Tanh, MD, PhD, a pediatrician and epidemiologist/infectologist at the University of Montreal, pointed out that Quebec seroprevalence surveys using residual blood samples from children and adults visiting emergency departments for any reason showed higher rates of prior infection than did the BC 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 U.S. and Canada.”

Dr. Quach-Tanh added that there is always a risk of bias with the use of residual blood samples, “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 has risen considerably, albeit variably by region, more than a third of the world’s population is still seronegative to the SARS-CoV-2 virus.

Dr. Skowronski reported institutional grants from the Canadian Institutes of Health Research and the British Columbia Centre for Disease Control Foundation for Public Health for other SARSCoV-2 work. Coauthor Romina C. Reyes, MD, chairs the BC Diagnostic Accreditation Program committee. Coauthor Mel Krajden, MD, reported institutional grants from Roche, Hologic, and Siemens. Dr. Germain and Dr. Quach-Tanh disclosed no competing interests relevant to their comments.

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