BY PAMELA FAYERMAN

The decision by the B.C. government to extend the interval between first and second COVID-19 vaccine doses to 16 weeks, instead of three or four weeks as recommended by vaccine makers, has caused plenty of consternation among physicians and other frontline healthcare providers, many of whom saw their second doses cancelled and postponed the very day they were to be given.

B.C. announced the change at the beginning of this month, just days before the National Advisory Committee on Immunization (NACI) issued new recommendations that were in line with what Dr. Bonnie Henry, B.C.’s provincial health officer, had announced as a new strategy. She knew that NACI would be endorsing the change so she didn’t hesitate to announce the decision in advance.

In the time since the controversial announcement, B.C. has been able to stretch precious vaccine supplies but many believe the policy is an experiment playing out in real-time since it hasn’t even been four months since Canada started vaccinations. Thus, no one can say with any certainty whether the calculated gamble will reap benefits, risks or a bit of both.

When doctors prescribe medications or other treatments in a manner that deviates from evidence in clinical trials and pharmaceutical recommendations, it is called off-label prescribing. A team of Royal Columbian Hospital (RCH) experts decided to look at the off-label 16-week interval in vaccine dosing to find a rationale for it and to see what evidence existed for potential harms and benefits of the extended interval.

The team is comprised of Dr. Tonia Tauh, Dr. Paula Meyler, Dr. Susan Lee and Michelle Mozel – all affiliated with the Royal Columbian Hospital Department of Anesthesia COVID-19 Working Group Research Team.

The RCH reviewers published their first review in the March issue of the B.C. Medical Journal and when B.C. changed the dosing interval, they published an update in the latest April issue.

Dr. Tonia Tauh

In an interview today, Tauh agreed that B.C. has pushed the envelope far beyond what any other jurisdiction has done. What Tauh and her colleagues found from delving into the clinical trial data and looking at evolving experience around the world is at once reassuring and slightly concerning.

Looking at “real-world” data from jurisdictions like the United Kingdom where the gap between first and second doses is 12 weeks, they note that in a UK preprint report (not yet peer-reviewed), a 60% to 70% level of protection was achieved in adults over the age of 70 after only one dose with either the Pfizer-BioNTech or Oxford-AstraZeneca vaccine. The protection was sustained during a follow-up period of 56 and 41 days, respectively.

But there is no data beyond that to show how durable immunity may be.

“Protection against symptomatic disease was further increased to 85% to 90% following the second dose of Pfizer-BioNTech vaccine. Among those who were symptomatic, the risk of hospitalization and death was reduced by 44% and 51% respectively, after a single dose of Pfizer-BioNTech, compared to an unvaccinated group. These data are encouraging when you consider that the UK variant (VOC 202012/01) was dominant during the study period.

“Encouragingly, asymptomatic disease and viral loads also appear to be reduced after the first vaccination dose. However, given that less than four months have passed since the vaccine was approved in any jurisdiction, longer-term data are not yet available. While there is biologic plausibility to surmise that these novel vaccines might provide months of protection like other protein-antigen-based vaccines, preprint data from Scotland show higher vaccine efficacy at day 28 to 34 compared to day 35 to 42 following a single dose of Pfizer-BioNTech or Oxford-AstraZeneca. The significance of this, or whether there is a further decline in immunity beyond day 42, is not yet known.”

Tauh said less than four months have passed since vaccines have been approved in any jurisdiction so proof for any approach to longer dosing intervals is still lacking.

“While there is biologic plausibility to surmise these novel vaccines might provide months of protection…preprint data from Scotland show higher vaccine efficacy at day 28 to 34 compared to day 35 to 42 following a single dose of either vaccine,” the authors state.

But Tauh said it is “reasonable to accept the risk of an extended dosing interval in order to get as many people as possible protected, sooner.”

“I think we’re cautiously optimistic that this won’t cause harm. And it is for the greater good to wait to see if it makes a difference.

“Right now, the B.C. interval is 120 days but if the vaccine shortage continues, and we get more data showing immunity is maintained, then we could see the interval extended even more.

“(But) vigilance will be key in determining whether this practice can continue safely while vaccine supply is limited; if the extended gap is found to put those waiting for dose two at excessive risk, then a shorter interval would need to be reconsidered,” the authors state.

Data shows that protection against symptomatic disease was further increased to 85% to 90% following the second dose of Pfizer-BioNtech vaccines. Among those who still got COVID even after being vaccinated, the risk of hospitalization and death was reduced by 44% and 51% after a single shot, compared to those who were unvaccinated.” In other words, there is still a not insubstantial risk of getting COVID even after second shots.

Dr. Henry has assured B.C. residents that the B.C. Centre for Disease Control will be monitoring the situation to see how many cases of COVID and outbreaks occur during the long interval between first and second doses. The authors reinforce this need for close attention to any signals of risks.

“Vigilance will be key to determining whether this practice can continue safely while vaccine supply is limited; if the extended gap is found to put those waiting for dose two at excessive risk, then a shorter interval would need to be reconsidered.”

pamela@medicinematters.ca