Why Canada's decision to delay 2nd doses of COVID-19 vaccines may not work for everyone
Small, pre-print study suggests elderly among those who may benefit from quicker timeline
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New research from two small pre-print studies suggests delaying second doses of COVID-19 vaccines by up to four months may not be the best approach for some older Canadians.
The research comes as some experts are also questioning whether Canada's vaccination advisers, who recommended the delay, can keep up with rapidly evolving science during the pandemic.
Prior to the pandemic, the National Advisory Committee on Immunization (NACI), which has provided guidance to the federal government on vaccinations since 1964, met just three times a year to discuss issues related to vaccines for influenza, mumps, measles and other viruses.
But a year after the pandemic was declared, with new data emerging daily, NACI has been thrust into the spotlight and forced to evaluate new vaccines for a novel virus faster than ever before.
"NACI's committees are basically made up of volunteers, many with heavy daily responsibilities during the pandemic," said Dr. David Naylor, co-chair of Canada's COVID-19 Immunity Task Force.
"There's no precedent for NACI to operate at this pace, and everyone is adapting on the fly."
NACI has met nine times since Canada approved its first COVID-19 vaccine on Dec. 10, but it has plans to ramp up in the coming months with another 13 meetings scheduled between now and the end of June.
The committee has previously overturned its initial guidance against immunocompromised individuals and pregnant women receiving COVID-19 vaccinations, as well as a controversial decision against the AstraZeneca-Oxford vaccine for those over 65.
Delay could leave cancer patients less protected, U.K. study suggests
Perhaps one of NACI's most impactful recommendations on Canada's vaccine rollout was the decision to delay second doses beyond manufacturing guidelines by up to four months, but emerging research signals it may not be the best approach for vulnerable Canadians.
A new pre-print study, which has not yet been peer reviewed, analyzed 151 older cancer patients and compared their immune response with 54 healthy adults after receiving the first and second doses of the Pfizer-BioNTech COVID-19 vaccine in the U.K.
The researchers concluded that delaying second doses to between eight and 12 weeks for most cancer patients left them "wholly or partially unprotected" and had implications on their health and the potential emergence of coronavirus variants.
WATCH | Delaying some 2nd COVID-19 vaccine doses challenged by new data:
"Our data advocates that bringing forward the second dose of the vaccine for patients who have cancer may benefit them," said Leticia Monin-Aldama, lead author of the study and a researcher at the Francis Crick Institute in London.
"And that perhaps a sort of one-size-fits-all approach may not be ideal when delivering these vaccines to the population."
NACI advocated for that universal approach to delay second doses by up to four months for all Canadians — the longest interval recommended by a country so far — based on limited real-world evidence and the reality of Canada's vaccine supply.
The decision was also informed by findings from Dr. Danuta Skowronski, epidemiology lead at the British Columbia Centre for Disease Control (BCCDC), who determined that one dose of the vaccine was actually more effective than clinical trials had initially shown.
NACI said if second doses were stretched to four months across the country, close to 80 per cent of Canadians over the age of 16 could get at least one shot by the end of June.
But Canada's chief science adviser, Mona Nemer, has said the decision to delay second doses amounted to a "population level experiment" and advised against the delay in older Canadians on CTV's Power Play this week, citing a lack of data to back up the decision.
Darryl Falzarano, a research scientist with the Vaccine and Infectious Disease Organization (VIDO) lab in Saskatoon, is also against the decision to increase the time between doses and said there is a growing body of research that suggests it's not the safest approach for immunocompromised and older adults.
"The initial data look like delaying the dose of the mRNA vaccines would still provide reasonable protection to the population from severe or moderate disease, and so vaccinating more people was looked at as the greater good," he said.
"Now, in certain populations — older people, people with comorbidities and cancers — likely delayed boosting for them is sub-optimal and possibly will lead to revised recommendations for those groups."
B.C. study analyzed long-term care residents
A second pre-print study released this week from researchers in British Columbia, which has also not been peer reviewed, cast further doubt on the dose delay for seniors and found that their immune response may not be as strong as in younger, healthier people.
The study analyzed antibody levels in a dozen long-term care residents in Vancouver a month after receiving their first dose of a COVID-19 vaccine, compared with 22 younger health-care workers — 18 of whom had not previously been infected by COVID-19 and four who had.
"The level of antibodies in older residents was fourfold lower, so significantly decreased," said Dr. Marc Romney, a clinical associate professor at the University of British Columbia in Vancouver and one of the authors of the study. "The function of those antibodies in older people was also compromised."
Romney said antibodies are just part of the picture, and he also plans to look at the immune system's full response in future research. But he said the fact that antibodies in the elderly didn't neutralize the virus as well as in the younger health-care workers suggests the dose delay may need to be revised for them.
"There is emerging evidence that demonstrates that there are some populations that will probably not fare as well and have the same degree of protection following single doses of a vaccine," said Dr. Isaac Bogoch, an infectious diseases physician and member of Ontario's COVID-19 Vaccine Distribution Task Force.
"These are groups you would want to shorten the time between dose one and two."
WATCH | The science behind delaying the 2nd dose of COVID-19 vaccines:
'This isn't a regular vaccine'
The speed with which NACI members are able to make these decisions has come under fire.
Falzarano said NACI is typically used to working under a "slow-moving" vaccine regulatory process where vaccines can take up to a decade to go from research to rollout.
"Their job is to review vaccines, but their experience is reviewing them under a much different scenario," he said.
"They are normally looking at a full data set when they have to make decisions. They would normally make very conservative decisions, and now, they find themselves in a much different scenario than what they're used to — and I think that's highly challenging for them."
NACI's decision to recommend against the AstraZeneca-Oxford shot for seniors on March 1 came despite emerging evidence from around the world demonstrating its ability to prevent severe COVID-19 in older adults.
But that guidance changed on March 16 after more real-world data on the vaccine's effectiveness was reviewed by NACI, and CBC News broke the story revealing documents on the federal government's plans to allow those 65 and older to receive it.
Alyson Kelvin, an assistant professor at Dalhousie University and a virologist at the IWK Health Centre and the Canadian Centre for Vaccinology, all in Halifax, said NACI should include more experts in emerging viruses and vaccine development to help navigate the research in the pandemic.
"This isn't a regular vaccine that's gone through the typical workflow for vaccine approval and vaccine development because it's an emerging virus," said Kelvin, who is also evaluating Canadian vaccines at the VIDO lab in Saskatoon.
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"You need somebody who understands that dynamic, instead of what we would normally depend on for our medicines or vaccines."
Dr. Caroline Quach-Thanh, who chairs NACI, responded to criticism during a news conference on March 16, saying that as new evidence emerged on the efficacy of the AstraZeneca-Oxford vaccine in older adults, NACI was "busy with other files" that delayed its guidance.
"The committee is very busy, obviously, meeting weekly to discuss the emerging data on these important topics," said Matthew Tunis, executive secretary to the committee.
"So there's always inevitably going to be a bit of a lag between when a committee deliberates and when the advice is made public."
Decisions take time, NACI chair says
Quach-Thanh responded to further questions about the delay in revising recommendations on CBC's Power and Politics on Wednesday, noting that NACI isn't equipped to review new evidence one day and make recommendations the next.
"It's not possible, we can't be that reactive," she said. "I don't think any advisory committee can be that reactive because it would mean that every time something changes, you move the needle one way or the next.
"Then it just means that you're changing your recommendation every other day. So you need to gather that base of evidence before you change something."
But even after NACI has finalized its recommendations, Quach-Thanh said, it takes an entire week to translate and upload them to the Public Health Agency of Canada's website — precious time in a pandemic where new data emerges daily.
Quach-Thanh said the committee is currently re-examining its guidance based on new research, and new guidelines on the timing of second doses for seniors and the immunocompromised could come as early as next week. But Skowronski, with the BCCDC, said it's too early to make that call definitively.
"This is a kind of a signal that we might want to follow, it's of interest, but we cannot change or make policy on the basis of this sort of small study," she said.
"It may come to pass that we will want to adjust depending upon how far we have come in achieving that goal of getting at least one dose into these individuals at highest risk."
Skowronski defended the decision to delay second doses by up to four months in Canada and stressed that the benefits of vaccinating more vulnerable groups with an initial shot outweigh the risks of delaying a second.
"My preoccupation is in at least getting a first dose into those at high risk of severe complications, and we've not achieved that yet," she said, adding that age was by far the biggest risk factor for severe outcomes from COVID-19.
"That's job one. Let's get that job one done, and then let's debate the timing of the second dose."
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