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AstraZeneca’s Phase III vaccine reduces symptomatic cases, not asymptomatic spread

COVID-19 cases fall with AZ/Oxford vaccine, but asymptomatic positives don’t differ from control

COVID-19 cases fall with AZ/Oxford vaccine, but asymptomatic positives don’t differ from control.

With evidence mounting that COVID-19 vaccines can prevent severe disease, the question now is whether they also prevent transmission. AstraZeneca’s latest data provide the first insights and suggest the shots should reduce overall transmission but may not solve the problem of asymptomatic spread. 

The results, according to a Lancet preprint posted Feb. 1, show an overall decrease in the total number of cases among vaccinated individuals, but the same number of asymptomatic cases in the control and vaccinated groups. The decrease in total cases, as with other vaccines that have shown efficacy, would likely decrease transmission, but the asymptomatic results indicate vaccinated individuals can still harbor the virus, and therefore likely spread it as well. 

AstraZeneca plc (LSE:AZN; NYSE:AZN) and the University of Oxford are the first to ask the question —the other front-runner vaccine manufacturers designed their protocols to measure prevention of symptomatic disease, with PCR testing used only in patients with symptoms to confirm disease.

The Phase III U.K. trial of COVID-19 Vaccine AstraZeneca (formerly AZD1222), in contrast, performed weekly PCR tests on all participants, even those without symptoms. 

The data are still somewhat muddied by the unplanned protocol shifts that resulted in different dosing amounts and schedules.  

In a pooled analysis of Phase III studies from the U.K., Brazil and South Africa, two standard doses of the vaccine reduced the total number of PCR-confirmed symptomatic cases by 63%, at least 14 days after the second dose. 

The study also looked at single-dose efficacy in that cohort using PCR testing in the interval between the two doses. Among subjects tested 22-90 days after the first dose, PCR-confirmed symptomatic cases were 76% lower in the vaccine group, after which protection dropped markedly, with 32% fewer compared with controls tested between days 90 to 120.

The U.K. study found no evidence that a standard two-dose regimen (SD/SD) reduces asymptomatic cases.

“There were 130 cases of asymptomatic infection occurring more than 14 days after the booster
dose,” the authors wrote in the Lancet preprint. “In the SDSD cohort there was no evidence of protection.”

In the U.K. COV002 trial, 83 of the 130 cases were in the standard dose cohort. Within that cohort, 41 (1.5%) vaccinated participants had asymptomatic disease during the study vs. 42 (1.5%) in the control arm. The number of patients in the vaccine and control arms was comparable, with 7,201 in the SD/SD vaccine arm and 7,178 in the control.

Those results indicate that people who have been vaccinated are just as likely to have asymptomatic disease as those who haven’t, so while overall spread may be reduced, the risk of asymptomatic patients unknowingly spreading the disease appears unchanged.

Dosing implications

When it comes to preventing symptomatic disease, the pooled analysis shows efficacy consistent with the interim readout reported in December, and builds the case for spacing out doses. 

The new analysis includes 332 cases, 201 of which were not previously reported. Overall efficacy in participants who received two doses — including both SD/SD and low dose/standard dose (LD/SD) regimens — was 66.7%, down slightly from the 70.4% reported in Lancet in December.

Among individuals who received the SD/SD protocol, which is the authorized regimen, there was 63.1% efficacy. The LD/SD regimen produced 80.7% efficacy (not shown below); however it was based on 2,798 subjects rather than 14,379. 

The study also broke out efficacy of the SD/SD regimen by the time between the first and second doses, showing a gradual increase from 54.9% for participants dosed less than six weeks apart to 82.4% for participants dosed more than 12 weeks apart. 

The study also looked at single-dose efficacy in the SD/SD cohort using PCR testing in the interval between the two doses. Among subjects tested 22-90 days after the first dose, efficacy, as defined by PCR-confirmed symptomatic cases, averaged 76%; after 90 days, protection dropped markedly to 32% for tests from days 90 to 120.

In late December, the U.K.’s Joint Committee on Vaccination and Immunization made the controversial recommendation to extend the interval between doses of AstraZeneca’s vaccine to 4-12 weeks to increase availability of initial doses. The new data back that move.

The new data do not, however, shed new light on efficacy in elderly patients, where the potential for waning protection has been a concern. The over 55 population has been underrepresented in AstraZeneca’s studies. The company previously reported just five cases in the age group, and the new preprint study does not break out efficacy by age.

AstraZeneca previously said upcoming results from an ongoing Phase III trial in the U.S. should provide clarity on vaccine efficacy in the 65 and older population. The study is enrolling adult participants, with data expected this month.