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Fourth doses of COVID-19 vaccines are rolling out to more Canadians as eligibility opens up across the country, but research suggests there are limitations to the impact they can have on the highly contagious BA.5 Omicron subvariant fuelling Canada’s first summer surge.
After growing pressure from health-care workers and the general public for access to additional shots, some provincial governments have expanded eligibility from just immunocompromised and older Canadians to anyone over the age of 18.
But the move contradicts the National Advisory Committee on Immunization (NACI)’s recent recommendations that a second booster should only be given now to those at highest risk of severe COVID-19, while younger Canadians could wait until the fall.
Data shows that while a third dose offers a significant increase in protection against infection, hospitalization and death — a fourth dose gives only marginal benefit against severe COVID-19 for most, including short-lived protection against infection, even in vulnerable groups.
“That fourth dose does add a small, modest decrease to your risk of developing severe illness,” said Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan.
“But I think that also it’s limited what we can expect from it — I don’t think certainly that we can expect it to stop this wave.”
BA.5 has sparked an unexpected seventh wave across much of Canada, accounting for close to 40 per cent of cases and leading to a significant rise in COVID-19 hospitalizations, due to its ability to evade protection from both vaccination and previous infection.
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4th dose protection against infection short-lived
A recent study from Israel published in the New England Journal of Medicine (NEJM) found that while protection against infection and severe COVID-19 increased after a fourth dose in those over 60, the effectiveness of the vaccine against infection began to wane after just several weeks.
A second study from Israel published in the British Medical Journal (BMJ) found that while people aged 60 and over gained additional protection against hospitalization and death in the three weeks after a fourth shot — protection against infection “quickly decreased.”
Health-care workers were looked at specifically in another Israeli study published in NEJM that found a fourth dose provided only a marginal difference in infection rates compared to those with a third shot, and only a slight difference in severity of breakthrough symptoms.
A new Canadian study published in the BMJ analyzed the effectiveness of a fourth dose on Ontario long-term care residents. It found the shot initially improved protection against infection and severe COVID-19, but the duration of that protection “remains unknown.”
“The science around this right now only has clearly demonstrated benefits of that fourth dose of the vaccine for the groups that (NACI) has outlined,” Dr. Fahad Razak, an internist at St. Michael’s Hospital in Toronto and the scientific director of Ontario’s COVID-19 Science Advisory Table, told The Current on July 7.
“Which is older individuals and individuals who are immunocompromised or high risk.”
Research suggests that while there are some people who do benefit from a fourth dose, including long-term care residents, the elderly and other vulnerable groups, data showing a clear benefit to those under the age of 60 is lacking.
Dr. Zain Chagla, an infectious diseases physician at St. Joseph’s Healthcare Hamilton and an associate professor at McMaster University, said older, immunocompromised Canadians can benefit from a fourth dose — but younger groups derive “very minimal benefit.”
“I don’t think there’s going to be a huge benefit here. It certainly will not change pandemic dynamics in terms of less disease. Really, to get any effect of taking the edge off, you’d need almost everyone getting fourth doses almost immediately at once,” he said.
“And even then, look, their immunity is going to wane in six to eight weeks and you’re going to see that they’re not really going to be protected against infection anyways and BA.4 and BA.5 will still be here in six to eight weeks.”
3rd doses uptake still lacking in Canada
While expanding fourth doses to more Canadians now could have a limited impact on the trajectory of the BA.5-driven wave in much of the country, the bigger issue lies with the abysmal uptake of third doses across the country.
Less than half of Canadians have received a third dose, which research suggests adds significant protection against severe COVID-19, a number that has remained stagnant for months amid the growing push to expand fourth doses.
“The biggest issue right now is the substantial number of Canadians who have not had a third dose,” said Dr. David Naylor, who led the federal inquiry into Canada’s national response to the 2003 SARS epidemic and now co-chairs the federal government’s COVID-19 immunity task force.
“It’s increasingly clear that table stakes for this vaccine are three shots, and we need to stop referring to people with two doses as fully vaccinated.”
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But Naylor is hopeful that expanding fourth doses to more Canadians could have an impact on the spread of BA.5 across the country, even if the data doesn’t show a clear benefit for younger age groups yet.
“For someone younger and healthy who has three shots and has had a recent infection, I can see the logic in waiting to get a fourth shot,” he said.
“There’s no question the marginal yields of a fourth dose are small at an individual level for that population segment — but they are at risk of reinfection and wider coverage may help to slow spread at a population level.”
Chagla said that expanding fourth doses to younger Canadians now in contradiction to NACI’s guidelines could actually do more harm than good in encouraging more people to come back for a third shot.
“There are going to be people that say, ‘Well, I’m on dose two, they’re already saying I need a fourth dose, what is the point of these vaccines if they didn’t protect me from getting Omicron?'”
“Every one of these doses that goes out, public image of what vaccines can do changes with them and we need a lot of people to come back for their third dose.”
Rasmussen from the University of Saskatchewan said her concern is that many Canadians may regard boosters as “optional” with limited benefit to immunity. She said messaging around third doses needs to be “hammered home” to increase uptake.
“That third dose does provide a significant boost in protection both against severe disease and against infection with Omicron BA.1,” she said.
“That fourth dose is maybe incremental, maybe just a modest benefit, but the third dose I think it’s very clear. At least with BA.1, it does provide significant benefits.”
Updated vaccines on the horizon
Timing boosters to ensure robust immune protection against COVID-19 is becoming increasingly critical with the emergence of Omicron’s highly contagious subvariants BA.4 and BA.5, as well as a concerning new subvariant driving a surge in India called BA.2.75.
While Canadians who opt to get a fourth dose of the original vaccine strain now may only be protected for several weeks against infection, updated bivalent vaccines that combine the original shot with protection against Omicron are also on the horizon.
Moderna’s bivalent vaccine is one many are pinning their hopes on. But experts worry targeting the original Omicron strain may not be sufficient due to research showing a lack of cross protection immunity against the vastly different BA.2.12.1, BA.4 and BA.5 variants.
“The usual argument for waiting is that we may get better vaccines in the fall. However, the data on bivalent vaccines are less compelling or complete than many of us had hoped,” Naylor said.
Bivalent vaccines target the spike protein of the virus. They are different from newer, innovative platforms with new targets or modes of delivery like intranasal boosters or pan-coronavirus vaccines.
“It’s been a mug’s game to guess what the virus will do next, and those who get a fourth dose in the near future will still be eligible for any new formulations starting in mid-October or thereabouts.”
These new vaccine technologies can potentially spur a more robust immune response, due to the fact that they stimulate another arm of the immune system or target multiple different coronaviruses altogether.
“We don’t know when those paradigm-shifting vaccines will be available, but it could be a while — particularly if we wait as seems only prudent to get really good data on their effectiveness and safety,” Naylor said.
“To me, that reality plus the ongoing spread of BA.5 together argues for getting on with a fourth shot even if it is more of the same with modest marginal yields.”
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Rising cases have prompted some provinces to declare a seventh wave of COVID-19, which is sparking concern for many health-care workers.
But Chagla said Canadians need to start thinking about the protection COVID-19 vaccines offer differently than they did before. There are going to be “limits” to what they can and can’t do at both an individual and population level going forward, he said.
“The first two doses did incredible things to the world and really changed the disease and actually did alter disease dynamics, and the third dose was able to save a lot of people from severe Omicron,” he said.
“But the way this virus has evolved and the way our vaccines are … they’re not going to be a long-term solution in preventing transmission, and there’s no guarantee with an Omicron-specific vaccine that it’s going to offer anything different.”
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