New data out of Israel suggests protection vs. transmission may start 2 weeks after Pfizer 1st dose

The rapid vaccination of the population of Israel with the Pfizer/BioNTech vaccine coupled with its centralized universal healthcare system and rigorous electronic medical records provide outstanding opportunities to learn about the performance of this vaccine at the population level.

Israeli researchers are rapidly analyzing this data as it accrues and putting out almost daily preprints presenting results of analyses each day. This includes reports from in mid-January from Israeli health organizations Clalit and Maccabi that infections in the first 2 weeks after first dose were 33% lower in vaccinated than non-vaccinated groups, and a report on 1/29 from the Maccabi group suggesting a further 51% reduction in infections from days 1-12 until days 12-25 after receiving first dose, together suggesting that those vaccinated with their first dose have protection against infection. There was another report from researchers at Weizmann Institute of Science published on 2/3/21 showing a sharp reduction in cases and hospitalizations in the age groups and cities that were vaccinated first vs. those done later, as I discussed in a previous blog post.

Here I will report on two preprints released in the past few days that provide evidence that besides protecting against infection, the Pfizer vaccine substantially reduces viral loads for those infected starting two weeks after the first dose, which provides evidence for protection against transmission.

One report from MyHeritageLab, the company performing the most PCR tests in Israel, demonstrates a sharp decrease in viral load in the 60+ population after that group was vaccinated. A second report from a group affiliated with Maccabi health insurance organization shows suppressed viral load by factor of 4x starting 12 days after first shot, matching the time period in which protection vs. infection kicked in during the phase 3 study. I will briefly summarize and comment on these results here.

Data from PCR tests show sharp decrease in viral loads in the 60+ population

A preprint released this week looked at the Ct levels, also called "number of cycles", from 16,297 positive PCR tests between 12/1 and 1/31 from MyHeritage Lab, the largest testing lab in Israel. Although they did not have access to information on which tests were from vaccinated individuals or not, they shed light on post-vaccination reduction in viral load by comparing the change in mean Ct levels over time in the >60yr population that was rapidly vaccinated in January vs. the <60yr population whose vaccination has lagged behind by 3 weeks. Following is the key figure from their paper:

The sharp increase in average Ct value in the >60yr old population over time demonstrates sharply reduced viral loads once the vaccine has had time to kick in, with an increase from ~26.5 to ~27.5 corresponding to a reduction of 50% in mean viral load since the Ct is on the logarithmic scale. This provides some evidence that the vaccine might be reducing viral loads.

Data from PCR tests show vaccine reduces viral loads 4-fold starting 12 days after first dose.

A second preprint was released this week from a group affiliated with Maccabi health insurance organization that analyzed Ct levels from positive PCR tests from their members, but unlike the MyHeritageLab group, they had complete information on who was vaccinated and when so were able to perform a direct comparison of viral loads in vaccinated vs. unvaccinated people.

Israeli healthcare system

for some background, Israeli has a centralized healthcare system in which free healthcare is provided for all Israeli residents through one of 4 health insurance organizations, like HMO's in the USA. From largest to smallest, they are Clalit (4.5 million members, 51%), Maccabi, (2.37 million members, 27%), Meuhedet (1.2 million members, 14%), and Leumit (720k members, 8%).

At the time of this report analysis on 1/25/21, Maccabi reported 650,000 of its members (27%) had been vaccinated, and among them 2897 were found to have positive PCR tests after the first dose and before the second dose.

First, to address the vaccine skeptic's questions of "if the vaccine is effective, then why do we have positive SARS-CoV-2 tests after vaccination?": As seen in the phase 3 studies, the vaccine is not 100% effective, and some people may become infected after vaccination. However, note that 2897 infections out of 650,000 vaccinated corresponds to an infection rate of 0.45%, which is considerably lower than the infection rate in the Israeli population during that time. Based on the national Israeli data, the number of confirmed cases in the country increased from 428,510 on 1/1/21 to 613,340 on 1/25/21, showing roughly 2% of the Israeli population had positive PCR tests in January. As suggested by the other Israeli reports mentioned above, the post-first-dose infections rates are considerably lower than the unvaccinated population, confirming that the vaccine confers protection vs. infection even after the first dose.

For the present report, the researchers plotted the Ct levels indicating viral loads for the 2897 individuals infected after their first dose as a function of days since first dose:

These data show a clear, sharp reduction in viral loads around day 12 after first dose, with the change in mean Ct from 25 to 27 suggesting a 4-fold reduction in viral load. This type of reduction in viral loads would suggest these individuals would be much less likely to transmit the virus to those around them based on the emerging literature linking viral load and transmission (e.g. like this one).

To assess whether the vaccinated individuals had lower viral loads than unvaccinated individuals, they found a set of 2897 infected unvaccinated individuals in their health system matched in terms of age and sex, factors known to impact viral loads, and compared the distribution of Ct in unvaccinated infected vs. those infected in days 1-11 after first vaccine dose (N=1755) and those infected days 12-28 after first vaccine dose (N=1142):

It is clear that the distribution of viral loads in those infected in days 1-11 after first vaccine dose were identical to those infected in the unvaccinated group, but the viral loads of those whose infection was detected on days 12-28 after first dose were systematically lower than those in the unvaccinated group, again by a factor of about 4x.

Conclusions:

These data together provide more evidence that the Pfizer vaccine confers substantial protection against infection and transmission starting about two weeks after first dose, which corresponds to the time point in which the phase 3 studies demonstrated protection against infection starts, the time at which the vaccinated and placebo groups clearly begin to separate in terms of cumulative infection rates (see figure below from Pfizer FDA report)

While secondary transmission studies would provide more rigorous evidence for reduction of transmission, given the clear link between viral loads and transmission evident in recent papers, the fact that these Israeli results demonstrate a sharp reduction in viral loads 12 days after first injection is compelling evidence for reduction of transmission.

Together with the other reports on infection rates, these results also provide some support that the protection vs. infection and transmission starts once the first dose kicks in. Although it is still controversial to consider delaying the second dose in favor of vaccinating more of the population with the first dose, this provides some data to support first dose efficacy.

I look forward to future analyses from these rich Israeli data, which in time should be able to assess whether:

1. the reduction in infections and viral load is even greater after second dose,

2. the rates of deaths and serious adverse events are similar in vaccinated and non-vaccinated groups in the population study as they were in the phase 3 studies,

3. the efficacy and safety results are maintained over time, and

4. whether the community transmission in Israel is essentially halted after full population vaccination is achieved.