COVID-19 – Page 9 – Pediatric Infection Connection

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.

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.

Holding My Breath

Bud WiedermannSeptember 12, 2021Leave a comment

I feel a bit on the cusp of important news in the next few weeks. How much fallout will we have from the Labor Day holiday, resumption of football and other sports with variable COVID-19 mitigation strategies in place, and of course school openings? What will the FDA say about booster vaccine doses at their meeting on September 17? Will Pfizer submit data on vaccines for 5-11 year olds this month? By October we could be in a new era of the pandemic in the US.

Testing Asymptomatic Children in Schools

This is an important component of infection control in schools, in combination with vaccination of all eligible individuals, distancing of at least 3 feet between desks, contact tracing, air quality measures, and quarantine/isolation policies. None of these measures alone is likely to be effective without the full package in use.

A story in the September 12 Washington Post caught my eye, mentioning that 24 of 4109 asymptomatic children tested by DC public schools was positive for SARS-CoV 2. That's a rate of 0.6%. Keep in mind that, no matter how good the test is, with a prevalence that low even a highly specific test showing a positive result might still be more likely to represent a false positive than a true positive. I'm all for more testing in schools, just be warned about the difficulties in interpreting results for individual children.

New Therapies for COVID-19 Disease

I have the sense that the lay press isn't reporting a whole lot about this. Ivermectin does seem to get a lot of publicity, I still don't understand how it became so popular, but evidence to date suggests that this medication is an ineffective treatment. The better-designed studies suggest no benefit, but certainly we could still use some larger randomized controlled trials to help determine if there is a use for the drug. In vitro studies suggest it may have some antiviral effects, but in concentrations likely to be toxic to humans. It also has some anti-inflammatory characteristics that might be beneficial. It's not a particularly dangerous drug as long as you don't use the horse dosage!

I'm intrigued with early studies of fluvoxamine, an SSRI medication mostly useful for OCD and some related disorders. I'm waiting to see more data and would not at all recommend using this for infected children at this time. You might be interested in the TOGETHER trial, an adaptive design trial based at McMaster University and still ongoing. One pre-print (non-peer reviewed) study suggesting benefit of fluvoxamine in one setting is a good example.

Another Holiday Super-spreader Weekend?

Bud WiedermannSeptember 5, 2021September 5, 2021Leave a comment

I couldn't help thinking, as I channel-surfed through various college football, golf, and other sporting events on Saturday, that COVID-19 disease rates will see another significant spike in the coming weeks. I hope I'm wrong. Hand-wringing aside, I wanted to mention a couple issues that you might have missed this past week.

MISC-C Long-term Followup

I fall into the glass half full crowd when I read this report on 1 year follow-up data for 68 children in England. No deaths occurred and only 2 children required critical care readmission. Fourteen of 19 children with coronary aneurysms had resolution and all 39 with abnormal function but no aneurysms had returned to normal echocardiograms. Yes, I know it's just a few patients, but given how sick most of these kids are at the start I'm encouraged.

The Rule of 3's

This month could see data submitted to FDA requesting authorization for COVID-19 vaccines for children under 12 years of age. Because these trials are "immunobridging" studies, the key data in addition to safety are whether the immunologic responses are similar to those seen in adolescents and young adults who showed protection from infection in the larger efficacy trials.

Speaking of safety, you all have probably heard that FDA requested additional children ages 5 through 11 years to be enrolled in the mRNA trials. I was puzzled by this because the myopericarditis rates seen so far are pretty low, about 10 excess cases per million vaccine doses in a recent article. It would require an impossibly large number of children in a research trial to detect this, so I was even more surprised to hear FDA's Peter Marks state that the FDA was following the rule of 3's in trying to assess safety of these vaccines for serious adverse events. This rule is explained in an oldie but goodie review article in JAMA stating that, if no events occurred in n subjects we can be 95% confident that the highest chance of this event is 3/n. The number of subjects in these current trials are in the few thousands, so if the logic behind adding a few more is to satisfy cardiac inflammatory risk concerns the addition of a couple thousand more subjects probably won't answer the question. It may allow some reassurance that the rate isn't substantially higher than what is being seen in adolescents and young adults.

See You in September

Bud WiedermannAugust 29, 2021Leave a comment

This song (as covered by The Happenings in 1966) has always stuck with me. September is upon us and schools are opening across the country. This year, however, these openings bring a bit more fear and arguments than in past years.

Another Lesson on Mitigation in Schools

Many of you likely have heard about the outbreak in an elementary school classroom in California reported in an early release from the CDC on August 27. The setting was an unvaccinated teacher who otherwise was following all the rules and teaching in a classroom that was optimized for prevention of SARS-CoV-2 transmission. The teacher became symptomatic but kept working plus routinely took his/her mask off to read aloud to students in class. What happened next is well summarized in this diagram from the report.

Note that the desks are 6 feet apart, an air filter was at the front of the room, the door was kept open, and windows flanking 2 sides of the classroom were open. The distribution and timing of cases in the classroom strongly suggest the teacher was the source of infection at least at the start of the classroom spread.

Vaccination, masks, social distancing, and other mitigation strategies all are important to keeping our kids safe when school opens.

Weighing Vaccine Risk/Benefits for Younger Children

Michael Schwartz, a former CNH pediatric resident and 1 of only 3 people (my wife and 1 of my 3 sons are the others) that I know actually read this blog, asked a great question last week that I wanted to answer more prominently this week. The folks at CDC have been great about distilling risks and benefits of the COVID vaccines as various rare adverse events have come to light in adolescents and adults, but do we have equivalent data for younger children to weigh the risks/benefits if and when vaccines are authorized for younger age groups?

I'm pretty sure CDC has access to unpublished numbers that they are monitoring, but for us regular pediatric healthcare providers I think the best place for summaries of pediatric information is the AAP/Children's Hospital Association biweekly reports. At the last update on August 19, things of course aren't looking good. It will be interesting to see how this changes as more schools are back in session. Also, remember that these data summaries are only as good as the sources. For example, the state of Texas (my place of birth, I'm sorry to say) has quit reporting COVID-19 data as of July 22.

Tag: COVID-19