October 2021 – Pediatric Infection Connection

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.

A Lull in the Action

Bud WiedermannOctober 10, 2021Leave a comment

It was a quiet week for new information, at least from my perspective. I didn't see any strikingly new COVID-19 data that hadn't already been discussed at various advisory meetings or appeared online earlier. This week promises some items of interest including FDA VRBPAC meetings for review of Moderna and Janssen vaccine booster doses.

In the meantime, help us avoid at least one form of twindemic by getting flu vaccines for yourselves and your patients.

Bias in Healthcare Continues

An article in the Journal of the Acquired Immune Deficiency Syndrome caught my eye. Investigators enrolled 160 non-pediatric frontline care providers (OB/GYN, family medicine, internal medicine, emergency medicine, and preventive medicine) from 48 "hotspot counties" for HIV infection. Enrollees needed to be aware of HIV pre-exposure prophylaxis (PrEP) and serve populations that included adult Black women. They were randomized to receive 1 of 4 online vignettes and state their likelihood of discussing and prescribing PrEP to the patient in the vignette. The 4 stories were identical except for a history of injection drug use (does/does not) and race (Black/White). The providers also completed the validated Color-Blind Racial Attitudes Scale (CoBRAS). Stated briefly, the investigators did find a significant relationship between patient race and provider racism score with respect to provider expectations of patient adherence to PrEP which in turn appeared to affect their willingness to discuss and provide PrEP. High scores on CoBRAS (i.e. more tendency toward racial bias) correlated with more positive expectations for adherence by the White patient versus the Black patient. The study itself has many limitations, including the problem that answers to an online scenario may not represent real world practice behavior, but it is a cautionary reminder to all of us to be aware of intrinsic bias in medical practice.

Prediciting Flu

In the best of times, predictions of the extent and severity of an upcoming influenza season are, in my opinion, equally well served by astrologists or palm readers as by public health experts (OK, slight exaggeration). It wasn't a big surprise that we had basically no influenza in the US this past winter, but no one has any good idea of what to expect with influenza in the coming months. Recent experience in the southern hemisphere was relatively mild, but that information hasn't been very reliable in the past in predicting rates in the northern hemisphere. The fact that we have so many more individuals who were not exposed to influenza last year would suggest we are in trouble this winter, especially if we see low vaccination rates. Bottom line? The reason you see no web links in this paragraph is because I've found no convincing information that anyone has a line on what to expect in the coming months. Again I say please push those flu vaccines!

Thor’s Hammer to the Rescue?

Bud WiedermannOctober 3, 2021Leave a comment

This is not an immediate game-changer, but the possibility of an oral treatment for COVID-19 disease is a hopeful harbinger of a new era in the pandemic.

Molnupiravir - What is It, and What Do We Know About It?

According to the manufacturer, molnupiravir was named after Mjolnir, which, as all fans of Norse mythology or Marvel Comics know, is Thor's hammer. Unfortunately all we know about the recent study results is from the manufacturer's press release, not exactly an unbiased source. It states that the study was stopped early following a predetermined interim analysis that showed benefit of the drug compared to placebo in adults with mild to moderate COVID-19. The drug group showed 28/385 recipients hospitalized (no deaths occurred) at the 29-day follow-up period versus 53/377 in the placebo group, which included 8 deaths. Adverse events were similar in drug versus placebo recipients. I'm giving you the raw numbers to show you that these are relatively small numbers of people with short-term follow-up, so we still want to hear more about this, presumably from the FDA after data are submitted to them.

Molnupiravir is in the nucleoside analog drug class which also includes several anti-HIV and other antiviral drugs. The manufacturer states that it has efficacy against variants including delta. Although the overall efficacy might be considered modest at best, the availability of an oral treatment for COVID-19 could have a major impact in the US as well as globally. Several other manufacturers have studies of oral SARS-CoV-2 drugs in progress. This is just the start of what promises to be a real step forward. Of course, vaccinating the unimmunized will have the biggest impact on the pandemic, much more than any therapeutic intervention.

Is the End of the Surge in Sight?

If you look at almost any measure, new cases of SARS-CoV-2 infection are heading down lately, but what does this mean? The interpretation is tough because it's hard to know a unifying explanation for why things are heading down at this time. If you want to keep track of things, I'd recommend the CDC Data Tracker and, within that, the percent test positivity rates are probably most helpful. The New York Times continues their highly interactive data monitoring that can give you a quick look at local and regional numbers though not direct percent positivity rates.

Month: October 2021