COVID-19 vaccine – Page 18 – Pediatric Infection Connection

A Busy Week 2

Bud WiedermannNovember 7, 20212 Comments

I am always bemoaning the fact that I don't have a reliable crystal ball, but maybe I found one in this article in the Atlantic. I took the time to read it, even though we've had a very busy week.

Vaccines for 5-11 year-olds

I'm sure you all know by now that the CDC/ACIP met on November 2 and did recommend Pfizer's COVID-19 vaccine for all 5 through 11 year-old children, noting that benefits clearly outweighed risks in this population. The presentations on November 2 largely mirrored what was presented the previous week at the FDA/VRBPAC meeting. This final seal of approval on FDA's EUA set in motion a flurry of activity for healthcare providers and parents to start the immunization process. Families can consult vaccines.gov to look for vaccination appointments nearby.

Less well known, the announcement also created a new round for the original trial participants. I spent much of November 3 and thereafter contacting parents of 5-11 year old children in our trial to let them know whether their child received vaccine or placebo. We then scheduled placebo recipients to come to our clinical trials unit to receive the first dose of the vaccine; we started this on November 4 and it is proceeding very well. Needless to say, this is an important and exciting time for these families who truly are the heroes we all thank for making it possible to provide vaccine to this age group. More to come in the coming months for the younger kids!

Another Oral Drug for COVID-19?

I always cringe when a pharmaceutical company announces significant new findings without releasing detailed data, but still I was happy to see Pfizer's apparent success for a new oral therapy, PF-07321332/ritonavir. A clinical trial of this agent for non-hospitalized high-risk adults with COVID-19 was halted early after a previously scheduled interim data analysis showed efficacy. In subjects who received drug or placebo within 5 days of symptom onset, the study drug group showed 6 of 607 recipients hospitalized with no deaths, versus 41/612 hospitalized and 10 deaths in the placebo group. We'll see what the FDA says about the data, but this could add to the treatment armamentarium eventually. Currently there are no pediatric trials for this agent in clinicaltrials.gov, nor any for the other oral agent, molnupiravir, that looked promising in recent reports. Molnupiravir is a ribonucleoside analog, while the Pfizer product consists of 2 protease inhibitors.

A Big Week Coming Up

Bud WiedermannOctober 31, 2021Leave a comment

Now that FDA has authorized the Pfizer COVID-19 vaccine for children 5-11 years of age, we await the CDC/ACIP recommendations for use. And, somewhat hidden in all of this, what about the leading causes of death in children other than COVID?

Which 5-11 yo Children Should Receive COVID-19 Vaccine?

CDC didn't ask me, but my short answer is to recommend for all of them. The only scenario where this might not be true is if a child's risk of being infected with SARS-CoV-2 is extremely low for the next several months. Like for other respiratory viruses, science has difficulty predicting timing and intensity of infection surges, but most think it is unlikely we have seen the last of COVID-19 disease in this country. Also, even if a child was infected in the past, we have no idea how long any immunity might last nor how to use antibody testing to determine a specific child is immune. Yes, if vaccine is in short supply (which sounds like will not be the case), priority should be given to children living in areas with high infection rates, having underlying risk factors for COVID-19 infections, or having contact with others at high risk for complications.

FDA scientists presented 6 epidemiologic scenarios at last week's meeting, all leading to the conclusion that benefits outweigh risks for vaccination of children in this age group. Also, remember that these open public hearings involve a lot of thinking out loud by the members, not conducive to sound bites. These are experts with various backgrounds trying to think through the data in real time. Some of the press accounts failed to recognize this and reported concerns that in some cases overshadowed the vote of 17 in favor with 1 abstention and none against authorizing the vaccine for this age group.

COVID-19 is a Major Cause of Death in U.S. Children; What About the Other Causes?

The FDA/VRBPAC discussions mentioned the leading causes of death in children 5-11 years of age in the US. COVID-19 tied (with suicide) for 8th place in the past year, according to data in the CDC WONDER database. Let's not lose track of the others on the list. In order, they are accidents, cancer, congenital malformations, assault, heart disease, chronic lower respiratory disease, influenza and pneumonia, cerebrovascular disease, and septicemia. During the pandemic, regular medical care has understandably been overshadowed by COVID-19 concerns. Please encourage your families to continue to seek regular preventive care as well as illness care, rather than "putting it off" until SARS-CoV-2 calms down. We continue to see some children presenting relatively late in the course of their illnesses, sometimes resulting in an emergency situation that might have been avoided with earlier medical care.

Is the FDA Reading This Blog?

Bud WiedermannOctober 24, 2021Leave a comment

Well, I'm pretty sure they aren't. Nonetheless I was pleased that they authorized the mix and match strategy for COVID-19 boosters a few days after I described their process as antediluvian for not doing so. This allows much more flexibility to take into account individual patient preferences and circumstances plus streamlining boosters in nursing homes and other settings where not everyone has received the same primary series.

Vaccines for 5-11 Year-Olds?

The FDA posted briefing documents from Pfizer (81 pages) and FDA scientists (39 pages) on October 22. Needless to say I have poured over both of them, and it seems highly likely that the vaccine will be authorized at their October 26 advisory group meeting. Note that if this happens, the actual shots in arms must wait until after the CDC/ACIP meets to provide recommendations, originally scheduled for November 3, but the meeting date has been removed from their website at the time of this writing. In the meantime, pediatric practices would be wise to plan for rollout.

One of our readers, Dr. Michael Schwartz in Pennsylvania, wrote with some very important logistical concerns: how to do this without wasting doses but still accounting for those unscheduled drop-ins wanting vaccine. Thankfully the storage and handling requirements for the Pfizer vaccine have been eased somewhat. For the pediatric doses, which will be supplied in entirely new containers, the initial frozen storage is still at -90 C to -60 C, well below regular freezer temperatures. However, after thawing the vials can be stored at regular refrigerator temperatures (2 C to 8 C) unopened for up to 10 weeks. After an individual vial is entered and diluted it must be used within 12 hours. Each practice will need to figure out if this works within their system, but I suspect most that have utilized mass flu vaccine clinics in the past can use the same strategy here.

Mystery Solved?

In the August 15, 2021, posting in this blog I mentioned the mysterious finding of melioidosis cases in 4 individuals in the US. None had a history of travel to high-risk areas or connection to one another. This past week the mystery might have been solved as researchers discovered contamination of a particular brand of aromatherapy: Better Homes and Gardens-branded Essential Oil Infused Aromatherapy Room Spray with Gemstones "Lavender & Chamomile." Whole genome sequencing testing is pending, but PCR testing of the product did reveal Burkholderia pseudomallei. The product was sold at Walmart but as of October 21 has been removed from their online and brick-and-mortar stores. CDC issued a Health Alert Network message with advice for consumers and clinicians, worth reading.

Before the Flood

Bud WiedermannOctober 17, 2021October 17, 2021Leave a comment

I'll touch on 2 versions of flooding today, first with regard to the perhaps outdated FDA rules for acting on data in the midst of a pandemic and secondly with respect to the flood of calls and visits we all might experience if a COVID-19 vaccine is authorized for children later this month.

Has the FDA Become Antediluvian?

The term, said to have been used first in the 17th century, literally means "before the flood" (as in Noah, not Curt). I wasn't able to watch the FDA VRBPAC proceedings regarding Moderna boosters on October 14 but did catch almost all of the live presentations for the Janssen (J&J) boosters on October 15. I've perused all the meeting materials for both days. Suffice to say that this included a virtual "flood" of new data, but we should have formal ACIP/CDC recommendations for both sometime this week. Let me mention just 1 key study that leads to my charge of antediluvianism and is already misrepresented in the lay press.

The so-called "Mix and Match" study is an unpublished NIH-funded trial designed to determine whether it is safe to boost with a COVID-19 vaccine product different from that used in the primary series and to characterize the resulting immune response. Note that it was not designed to determine what is the best product to boost a particular primary series, but some pundits have attempted to skew the data to that purpose in spite of comments to the contrary by Dr. Kirsten Lyke who presented the data. While it is true that participants who originally received a dose of J&J vaccine had higher antibody levels when boosted with Moderna or Pfizer vaccines compared to a J&J boost, the study simply wasn't designed to know how that translates clinically. Limitations include the very small numbers of participants (50 in each of the 3 booster groups, or 150 total participants) as well as the short follow up period to date, only 29 days after the boosters. This is particularly important because it is already suspected that an adenoviral-vector vaccine similar to the J&J vaccine has very different antibody kinetics compared to the mRNA products leading to a much slower decline in antibody. With this difference, it could be that levels following a booster dose could continue to rise after 29 days and thus not yet detected in the NIH study. The NIH study is planned to measure these kinetics in the coming months. Also know that the trial enrolled down to age 18 years of age only.

I thought the FDA could have been a bit more flexible in allowing some conclusions regarding mix and match options starting even now, ergo my antediluvian reference. The study's safety data did not reveal any real concerns, and given those results I think it is biologically implausible that serious adverse events such as myocarditis are likely. Allowing mixing would make booster dosing much easier from a public health implementation standpoint. We'll see if some official FDA statement or ACIP recommendation permits mixing. Most importantly, in terms of public health no matter what we do with boosters the emphasis should be on vaccinating the unvaccinated.

Future Flood of Frantic Fonecalls

October 26 is circled and blocked off on my calendar. That's the day FDA/VRBPAC meets to discuss the Pfizer vaccine data for 5-11 year-old children. None of the meeting materials are posted yet, but it is likely that the antibody data in this immunobridging study look good if we believe Pfizer's press releases. What I'm not sure about is how much safety data FDA will require before authorizing use. This was a relatively small study, less than 10 thousand subjects even with an expanded safety cohort enrolled a few months after the start of the original study and thus shorter follow up period. If the vaccine is authorized for this age group, note that you can't use any old Pfizer vaccine stock you might have in your office. The doses are different and will be all new vials; it will take a bit of time to distribute.

Controversy Over Boosters

Bud WiedermannSeptember 19, 2021Leave a comment

This past week saw a bit of infighting at the FDA spilling over into the public. Two respected and seasoned staffers at CBER announced their resignation, apparently fueled by disagreements with White House statements about booster plans, and then they signed on to a Lancet article opposing booster approval. This was in advance of the FDA/VRBPAC meeting on September 17. I urge public officials on all sides to tone down their emotions and just get back to evaluating the evidence.

Mask Slackers

I'm always interested in the history of medicine and thus delighted to see this quick graphic article in the NEJM posted on September 18. The article is free without subscription, take a few minutes to look at it!

The Boosting Evidence

I was able to attend a good deal of the FDA/VRBPAC meeting, including the important discussions surrounding a vote about whether to approve boosters for all individuals age 16 years and above. The event showed some evidence of the earlier drama in the week but mostly was under control. I was very interested to hear discussion of data from Israel and I was in stats nerd heaven with the very cogent discussion of pitfalls in interpretation of "real-world" data. As you probably know by now, the advisory group voted 14-2 against approving the vaccine for everyone > 16 years of age, and in the ensuing discussions what emerged was a unanimous recommendation for authorization of boosters for individuals > 65 plus front line providers and others at high occupational risk like teachers. I think the committee made the right move for now.

Here are 3 takeaways from the meeting, some of which I don't think made it through clearly in the lay press. First, the data presented didn't have long enough follow up information to know whether boosters truly served to dampen the surge curve and significantly lessen morbidity and mortality in Israel. Similar data are lacking for what the US curve is doing now and whether the surge will decrease without immediate boosters. It will be only a few weeks until that information is available. Second, although the Pfizer data clearly show a robust "boost" to antibody in booster recipients, it's based on a small number (around 300) of individuals with limited follow-up. Historically, that number of study subjects is at the low end for what FDA has approved in the past for vaccine boosters, Japanese encephalitis vaccine being an example for that low number. Other booster approvals tend to have involved closer to 1000 subjects.

The third takeaway involves the important concern of safety. In particular, why expose young people to the possible myocarditis risk with a booster dose if the benefits to them and society are a bit fuzzy at present? I did learn that the best estimates for highest mRNA vaccine-associated myo/pericarditis is in 16-17 year olds at about 1 in 5000-6000 recipients. The rate goes down sharply with advancing age. This complication seems very mild at present, but we're still awaiting long-term follow-up of this potential side effect. I am less concerned about this factor than I am about the lack of high-quality evidence that boosters are highly beneficial this soon after primary series.

For those interested, I'll be discussing the booster considerations along with a general COVID-19 update and information about studies in younger children at a Children's National Hospital Pediatric Health Network Town Hall meeting at 12:15 PM EST on Tuesday, September 21. Organizers have told me you don't need to be a PHN member to attend the meeting. As I write this the morning of September 19, we await word from FDA as to official authorization of boosters and then the ensuing deliberations from the ACIP on more specific recommendations. Those meetings currently are scheduled for September 21 and 22.

Tag: COVID-19 vaccine