New research suggests COVID was less deadly than thought in first year of pandemic

Meta-research pioneer John Ioannidis of Stanford cuts "infection fatality rate" by half for age groups including young people, using international "seroprevalence" review.

Updated: January 18, 2022 - 11:49pm

COVID-19 was less lethal across nearly every age group in its first full year than previously thought, according to an updated review of global research from Stanford University's Meta-Research Innovation Center (METRIC).

Between summer and Christmas 2021, METRIC's estimates of deaths from infection fell by half in multiple age groups, including young people, and less sharply in others.

The international estimates, which have not been peer-reviewed, are not substantially different from the CDC's own "best estimate" of COVID mortality in the U.S., last updated in March. They use different age ranges, making exact comparisons difficult.

The findings raise questions about ongoing COVID restrictions and mandates, particularly for schoolchildren and college students, who remain at the lowest overall risk from infection. 

The risk-benefit ratio of vaccine boosters is also under scrutiny, with international authorities souring on their wide deployment and a new Israeli study finding that a fourth dose of the Pfizer or Moderna vaccines doesn't stop the Omicron variant.

METRIC codirector John Ioannidis, credited by one medical publisher as having "practically invented" the field of meta-research, warned early in the pandemic that available infection data were "utterly unreliable." 

His ongoing tracking of "seroprevalence," which measures COVID infection rates using the presence of antibodies in blood samples, has made him controversial in scientific circles. 

Ioannidis led a study in Stanford's backyard that estimated a much higher infection rate than local authorities were reporting in spring 2020, leading to criticism of his methods. The revised paper was published last spring in an Oxford medical journal.

He has also consistently emphasized that mortality risks for the non-elderly were "very small" even in COVID "hotbeds." A June 2020 review of seroprevalence studies determined a median "infection fatality rate" (IFR) of 0.26% overall and 0.04% for everyone under 70.

Ioannidis and METRIC postdoctoral fellow Cathrine Axfors published more refined IFR estimates in July based on 23 studies from 14 countries conducted in 2020.

They further refined those estimates in December with two additional studies. All but three studies were in "high-income countries" such as the U.S., while four of the 25 lacked "age-strata observations."

To be eligible for consideration, the studies had to have more than 1,000 participants 70 or older with COVID antibodies. (Ioannadis is primarily interested in tracking the IFR of "community-dwelling elderly populations.")

The age group 0-19 still has the lowest estimated IFR with 0.0013%, or 1.3 per 100,000, but that's half the IFR of July's study. Also halved: 20-29 year-olds with an IFR of 0.0088% and 40-49 with 0.042%. 

The only age group without a lower IFR in the December update was 60-69 year-olds, which increased to 0.65%. The community-dwelling elderly had an IFR of 2.9% and elderly overall 4.9%, but the study noted a "steeply increasing IFR with larger proportions of people" 85 and older.

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The study mentions Omicron once, saying preliminary data on the variant "suggest that it may be associated with even lower severity."

The Greece-born Ioannidis told the Greek Reporter this week that he believes the earlier Delta variant is responsible for a substantial portion of recent COVID deaths in the U.S. and Europe, with infections predating the Omicron wave.

"Omicron has the characteristics of an endemic wave,” he said, echoing South African research on Omicron infection providing some protection against Delta infection. 

The milder variant has a "seasonal appearance, high rates of transmission, [and] disproportionately low death burden in a setting where there is very high background immunity due to prior infection and/or vaccination," Ioannidis said.

The chief epidemiologist at Denmark's State Serum Institute made the same claim earlier this month, telling Danish TV 2 that "we will have our normal lives back in two months."

Tyra Grove Krause said her organization found the hospitalization risk from Omicron was half that of Delta. It welcomed the spike in cases in recent weeks, saying the "massive spread" of a mild variant will put the country "in a better place than we were before.'

Wall Street Journal editorial board member Allysia Finley went so far as to credit Omicron for a coming "superimmunity" wave that, thanks to the training it gives white blood cells, stops new variants and future coronaviruses from wreaking havoc.

Even before the Omicron wave, prior COVID infection was reducing hospitalizations for vaccinated populations experiencing breakthrough infections, according to research published last month by Microsoft's AI for Good Research Lab and a University of Washington infectious disease researcher.

The research team sought to discern the risk of hospitalization by vaccine type for breakthrough infections and how much a prior infection affects the severity of a breakthrough. Like METRIC's study, the preprint hasn't been peer-reviewed.

Using medical claims records from Change Healthcare and a study population "fully vaccinated" last spring, the researchers found subsequent hospitalization least likely for Moderna and highest for Johnson & Johnson vaccine recipients. 

But hospitalization was 50% lower and risk of death 75% lower among those with natural immunity "independent of age, sex, comorbidities, and vaccine type," the study found.

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