Mixing study reveals no safety concerns

Early results from U.K. report on vaccines show more side effects

A hotly anticipated British study has released early data showing no safety concerns for people who “mixed and matched” their COVID-19 vaccines, despite experiencing more minor side effects — preliminary findings that could inform Canadian regulators’ decisions on whether to approve vaccine mixing.

The data, published Wednesday in a peer-reviewed letter in the Lancet, comes from a University of Oxford study called Com-COV, which is investigating the safety and efficacy of combining different COVID-19 vaccines. The study’s results are being anxiously awaited by drug regulators around the world, amid growing concerns over rare but serious blood clots linked to the AstraZeneca and related Covishield vaccine.

This first batch of data shows no safety concerns in the seven days after people were given a second dose of Pfizer after first receiving AstraZeneca, a vaccine schedule many would like to see in Canada, where some people who have received AstraZeneca are now anxious for different options for their second dose.

The same was true for study participants who received vaccines in the reverse order. And although people who mixed vaccines were more likely to report minor or “moderate” side effects — like chills, feverishness and fatigue — these symptoms typically passed within 48 hours, and none required hospitalization.

This new safety data is a “good next step” toward deciding whether Ontarians can mix and match vaccines, according to Dr. Vinita Dubey, associate medical officer of health with Toronto Public Health.

“The top-of-mind questions for most people are ‘Is it safe?’ and ‘Does it work?’ ” Dubey said Wednesday, speaking to reporters during a press briefing organized by the Ontario Medical Association.

“This first data is going to help us answer, ‘Is it safe?’ ”

But the Lancet letter does not answer one of the most pressing questions now facing Canadian regulators: will two different vaccines elicit a comparable — or perhaps even superior — immune response? Data for answering this question, the primary one for Com-COV researchers, won’t be available until June, according to the paper.

The new data also comes from study participants who received a second dose after four weeks, a dosing interval that isn’t currently possible in Canada.

“We are delaying second doses for up to four months, and it’s not quite clear based on this data if people would have the same degree of side effects,” said Dr. Isaac Bogoch, an infectious disease specialist and member of Ontario’s vaccine task force. “And of course, what is the immunogenicity of this, how does the immune system respond? Those are our big questions.”

On Tuesday, Ontario announced the province was pausing its AstraZeneca rollout “out of an abundance of caution” after a recent increase in reported cases of VITT (vaccine-induced thrombotic thrombocytopenia), where people can develop serious blood clots that can lead to death or disability.

As of Saturday, Ontario has seen eight cases of VITT linked to adenoviral-vector vaccines like AstraZeneca or Covishield. More than 850,000 doses of these vaccines have been administered in Ontario, where the incidence for VITT is now estimated at one in 60,000, according to Dr. Jessica Hopkins, chief health protection and emergency preparedness officer with Public Health Ontario.

Several European countries, including Germany, France, Finland, Norway and Denmark, are already recommending that people who have been vaccinated with AstraZeneca should get their second dose with an mRNA vaccine, like Pfizer or Moderna.

Canada is likely to follow suit, according to Bogoch. But first, regulators are waiting to see more data, especially from the Com-COV study. “That’s the big one,” he said. The Lancet paper reported data from 463 people age 50 or older who enrolled in the ComCOV study and were randomized into four groups: people who received two Pfizer doses, two AstraZeneca doses, or a mixture of the two. Doses were given four weeks apart.

(Another group in the ComCOV study is getting jabbed 12 weeks apart, which is more aligned with Canadian vaccine schedules, but these participants are only now receiving their second doses. A second study, Com-COV2, is also investigating vaccine combinations that include the Moderna and Novavax vaccines.)

Among study participants who received AstraZeneca followed by a Pfizer “booster,” 34 per cent reported feeling feverish after the second dose — compared to just 10 per cent who got AstraZeneca for both doses.

For those who received the Pfizer first, followed by AstraZeneca, 41 per cent experienced feverishness after their second dose, compared to 21 per cent who got Pfizer for both doses.

Similar increases were also reported for other mild symptoms, including chills, fatigue, headache, joint pain, malaise and muscle ache, most of which passed within 48 hours. Nobody experienced thrombocytopenia, or low blood platelet counts, a condition associated with VITT.

Dr. Matthew Snape, ComCOV’s chief investigator, said the mild symptoms reported by study participants are “standard” side effects we might expect to see after vaccination, only they’re happening more frequently for people who mix and match.

He acknowledged that the study only looked at people over 50, so it’s possible that younger people — who tend to mount a stronger immune response — could experience more pronounced side effects.

“It’s really an intriguing finding and it’s not something necessarily we were expecting — to see such a consistent signal,” Snape told reporters in a media briefing Tuesday. “Whether or not this will (herald) an actual improved immune response, we don’t know yet. We’ll be finding out those results in a few weeks’ time.”