The last remaining group of people waiting for Covid vaccine eligibility is those under five years old, and the moment may finally have arrived. Pfizer and BioNTech announced that they would submit a request to the Food and Drug Administration in the next few days to amend the Emergency Use Authorization (EUA) for their pediatric vaccine to include children ages six months to four years old.

The vaccine will initially be two doses of 3mcg each, but they expect to add a third dose once data on the third dose becomes available in the coming months. When that data becomes available, the companies will submit it to the FDA to expand the EUA to include that third dose, to be administered at least eight weeks after the second dose.

It’s highly unusual for a company to plan for a three-dose regimen yet request a EUA before data for the third dose is available. Still, millions of parents across the US are likely grateful for the arrangement. Many have been anxious to begin rejoining society but waiting until they can vaccinate their youngest children, and the delays have been frustrating as infections in this population have climbed. The trials began in May 2021 and were expected to finish by the end of the year, but the company announced a setback in December.

Although the phase 2/3 trial showed the vaccine to be safe for all ages and effective for children aged six months to two years, the 3mcg dose wasn’t high enough for the ages two to four group. That’s when the company decided to add a third 3mcg dose for this age group in the trial, and results from that are expected by mid-2022. The problem is that no one wants to wait until mid-2022 to make vaccines available for the youngest folks. At the same time, even though the vaccine is effective for ages six months to two years, the FDA does not “jump” age groups (i.e., go from ages five to 11 to ages six months to two years without including ages two to four).

What’s Changed?

What’s surprising about this announcement is that no additional data from the trial has become available since the disappointing two through four age results were announced in December. That’s left some wondering why Pfizer/BioNTech has decided to ask for this temporary two-dose arrangement when the situation is the same as it was two months ago. The answer is likely the one thing that isn’t the same as two months ago: Omicron.

Omicron was still on the rise in December when Pfizer announced the under five results, and it hadn’t yet grown into the most significant wave of Covid since the pandemic began. As infections climbed, they hit the under five kids like everyone else. According to the American Academy of Pediatrics, more than 3.5 million cases were reported in children in January. New cases for just the week of January 27th were 808,000, lower than the million-plus reported in the previous week but still three times the highest level of Delta cases last year.

The proportion of children with Covid has also grown compared to other age groups. Since the pandemic’s start, pediatric cases have represented 16.8% of all US Covid cases. Still, pediatric cases in the last week of January made up 22.8% of all Covid cases—slightly higher than the percentage of children in the US population (22.2%). That means children are now disproportionately getting sick more often with Covid than other age groups, which makes sense given the low vaccination rates in kids over five and the lack of vaccines for kids under five.

Omicron cases do not cause the same high percentage of severe disease, hospitalizations, and deaths in children as in much older age groups. However, that doesn’t mean Covid isn’t a potentially serious disease for children, even those without underlying conditions. For example, in the states reporting hospitalization numbers, children make up anywhere from 1.6% to 4.4% of all hospitalizations, and approximately 0.1% to 1.5% of all Covid cases lead to hospitalization.

A small percentage of a large number is significant, meaning thousands of children are hospitalized and/or developing multisystem inflammatory syndrome (MIS-C). In addition, MIS-C tends to develop three to six weeks after Covid infections, so MIS-C cases lag about a month behind Covid infection numbers. That means a month after the Omicron surge subsides, hospitals will still see more children with MIS-C.

The Next Steps

Most people believe the Omicron surge and its disproportionate impact on children is the primary factor motivating Pfizer/BioNTech to request a EUA to get shots into small arms. However, Pfizer/BioNTech, like the FDA and the rest of the public health community, are also aware that Omicron may not be the last major variant. Despite the high numbers of infections from Omicron—which likely substantially increased population immunity to SARS-CoV-2—preliminary research finds a higher re-infection rate with Omicron than with past variants. Further, a new variant could have greater immune escape capability—the ability to get past immune defenses against previous variants—and cause another surge. As a result, public health experts are now hoping for the best but planning for the worst.

After Pfizer submits the under five data in the next week, the FDA will take four to six weeks to review the data. First, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), an external committee of experts who don’t work for the FDA and volunteer their time, may review the data and make recommendations to the FDA. VRBPAC did not review the data before the FDA issued a EUA for ages five through 11 vaccines, but it still could ask VRBPAC to look at under five data. The FDA does not have to follow recommendations by VRBPAC, but VRBPAC’s assessment carries a lot of weight when asked by the FDA to review data.

If the FDA does issue a EUA, the next step is for the CDC’s Advisory Committee on Immunization Practices (ACIP), another independent group of experts, to review the data and make recommendations to the CDC regarding vaccination in this age group. Nearly always, the CDC follows ACIP’s advice in making vaccination recommendations. (The only recent exception was when the CDC director expanded ACIP’s booster recommendations to include a larger group of occupations at higher risk of COVID exposure.) All of this is unlikely to transpire until late March at the earliest, but millions of parents remain hopeful that they’ll be able to vaccinate their littlest littles in the spring.