myocarditis – Page 3 – Pediatric Infection Connection

Winter Marches On

Bud WiedermannJanuary 30, 2022Leave a comment

It appears the feared double-whammy of simultaneous COVID-19 and influenza peaks won't happen. The CDC influenza data are a little harder to interpret because of the omicron peak affecting counts of influenza-like illness (ILI); ILI is high, though coming down, but likely most of the numbers are omicron, not influenza. Most of the influenza that is being identified is influenza A H3 which could contain a clade that has a bit of a mismatch with this year's vaccines. CDC's influenza web site is always informative.

More on Vaccine Myocarditis in Adolescents

The New England Journal published brief correspondence from Israel updating Pfizer vaccine-associated myocarditis in teenagers. The latest numbers, looking just at ages 12-15 years, are 1 case per 12,361 second vaccine doses in males and 1 per 144,439 in females. These numbers are in the same ballpark as previously reported in US and Israel. The current data are based on hospitalizations for myocarditis. Note that the illness still looks to be very mild so the Israeli data could be missing cases managed as outpatients.

UK.gov

My new BFF in the world of COVID-19 listservs is from the United Kingdom. I signed up for daily alerts a while back. They come through at around 3 or 4 AM Eastern time and range from 1 to many different updates. All have summaries and links to raw data. Some days I'm almost overwhelmed with new reports. The graphics aren't as attractive as CDC's web site, but in general I think the UK does a better job than CDC in explaining nuances to the general public. I'll highlight 2 reports from this past week. Browse through if you are interested, but it's a definite rabbit hole for COVID nerds.

First is a January 26 report with some interesting mathematical modeling that attempted to determine the numbers of adults who would have tested positive for SARS-CoV-2 antibodies from either vaccination or infection. Not surprisingly, the older age groups with positive testing likely would have been due to vaccination. Another portion of the report looked at children 8 - 15 years of age where of course relatively little of the antibody positivity would have been due to vaccination. This type of analysis is important in understanding new methods to track pandemic/endemic activity.

Friday's report, which generally includes the big picture infection survey for the week, also had a nice report on the BA.2 variant risk assessment; this is the omicron variant getting a fair amount of media attention now. They have a lot of background data elsewhere, but their one-pager is a nice overview comparing the BA.2 variant to BA.1, the original omicron variant. They expressed moderate confidence that there is evidence of community growth advantage for BA.2 in more than one country (Denmark seems to be the country with a lot of BA.2 at the moment). However, they felt only low confidence that increased transmissibility of BA.2 explains this growth advantage. Also with low confidence, they saw no evidence that BA.2 was more able to evade the immune system (i.e. vaccines or monoclonal antibody treatments less effective) compared to BA.1. They had insufficient data to comment on whether infection severity is different. For now, BA.2 is yet another variant to keep an eye on.

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.

Something to Distract You From the Bad Variant News

Bud WiedermannJuly 25, 2021Leave a comment

Things aren't looking great around the country, much less the world, as the delta variant shows just how effective it is at spreading including among vaccinated individuals. Here's a couple pieces of news to cheer you up.

School Bus Transmission May Not Be All That Terrible When Done Correctly

An observational study published online in the Journal of School Health suggests that spread of SARS-CoV-2 on school buses isn't that high. Investigators reviewed existing data from 15 school buses in Virginia between August 24, 2020 and March 19, 2021 when they were operating at near capacity. In general there were 2 students per seat, universal masking, simple ventilation strategies, and regular pooled saliva testing of everyone with confirmation of positives by a PCR nasal swab. They found 39 students who were positive but no apparent transmission on the buses themselves.

Of course this study has limitations, including the retrospective observational design that didn't allow confirmation of a lot of details, the small sample size, and perhaps most importantly the fact that this was all before the delta variant became dominant. Still, it does offer some reassurance regarding transmission on school buses.

GBS and the Janssen Vaccine

You might expect me to file the association of Guillain-Barre syndrome and the Janssen (Johnson & Johnson) vaccine as bad news, but the fact that it is still really rare is actually a good thing. The ACIP met on July 22 to discuss the situation; you can access the key slide deck online. With 12.6 million doses of the vaccine administered through the end of June, 98 cases of GBS have been reported. The highest risk group was men 50-64 years of age at 15.6 per million vaccine doses, still far below the risks associated with infection itself.

We now know of rare side effects with the 2 mRNA vaccines (myopericarditis) and with the Janssen vaccine (TTS (thrombosis with thrombocytopenia syndrome) and GBS). Still, these side effects are so rare that the benefits of vaccination clearly outweigh risks of serious complications from COVID-19 disease. Immunization is still the best choice for everyone.

Myocarditis Concerns, and Delta Marches On 2

Bud WiedermannJune 27, 20212 Comments

Better Data on Risks of Myocarditis and Pericarditis from COVID-19 Vaccines

The ACIP/CDC held their meeting, postponed from June 18 due to the new federal Juneteenth holiday, on June 24. It was worth the wait, and fortunately I was able to attend the meeting online. You can see all of the presentation slides on their website, in particular I'd recommend the risk-benefit discussion by Drs. Wallace and Oliver. I had 2 major take-aways from the approximately 5-hour presentation.

First, as more time and cases have accumulated, the link between vaccines and myocarditis/pericarditis in adolescents and young adults (primarily male) seems much more convincing. The timing after the second dose, the striking age distribution, and the mostly mild clinical features strongly suggest a link even though the rates are very rare. It is worth mentioning this potential risk to people considering vaccination, though in these same demographic groups the risk of adverse sequelae from COVID-19 disease itself is much higher. Also note that this association was seen with both of the mRNA vaccines, Pfizer and Moderna, but I don't think we have enough information yet to know if this will occur with other COVID-19 vaccines. The mechanism of injury is still unknown and is the subject of much research.

Second, recognize that the only reason this was brought to light so quickly is that we have very massive and effective surveillance of adverse events with these vaccines. Please encourage all of your patients to sign up for V-safe when they are vaccinated, and everyone should report any suspected vaccine adverse events to the VAERS system.

Delta Variant is a Real Problem Everywhere

Evidence continues to mount that the SARS-CoV-2 delta variant is a major problem worldwide. It is unquestionably more easily transmissible than other variants by a long shot. Both mRNA vaccines seem to provide very good protection against severe disease caused by the delta variant, though preliminary data suggests that a single dose, rather than the recommended 2 doses, is not very protective. The jury is still out about whether delta causes more severe disease than other variants, but clearly this is the strain responsible for the vast majority of hospitalizations in developed countries, primarily impacting children and young adults who represent a disproportionate number of unvaccinated individuals. It likely will be the dominant strain in the US in a matter of weeks. Please encourage everyone to be vaccinated.

Somewhat more in the rumor category, a "delta-plus" variant has cropped up in the lay press. It is a strain that carries an additional mutation, K417N, that was known to be present in the beta variant and has been associated with poor response to treatment with monoclonal antibody preparations. We still need more information about this new sub-lineage strain to know its clinical significance.

Coming Up For Air

Bud WiedermannJune 20, 2021Leave a comment

Well, vaccines are starting to turn the tide and even the cicadas are retreating now. I'm hoping to recommit to Pediatric Infection Connection this summer and try to post weekly commentary that will be at bit more concise than my traditional rambling style. I will try to limit myself to just 2 topics a week, but starting off I'm already breaking that pledge with 3 topics.

1. A Conflict of Interest

For the first time in maybe a couple decades, I need to declare a conflict of interest up front. I am overseeing the Pfizer COVID-19 vaccine trial at Children's National Hospital for children 6 months through 11 years of age. While I don't think this will color any of my commentary here, implicit bias has been recognized as a confounder in scientific and Evidence Based Medicine circles for many years. I will do my best to recognize that and be objective.

2. Keeping Straight with SARS-CoV-2 Variants

In case you hadn't noticed, the terminology for variants has changed yet again, I think for the better but also adding to the public confusion. The purpose is laudable: eliminating the possibly pejorative naming of variants by site of first detection and also doing away with confusing codes. I'm very much in favor of getting rid of the geographic references to outbreak agents. Some of you know that the 1918 H1N1 influenza A pandemic was also known as the Spanish Flu, but in fact the evidence would suggest that a better name is the Kansas flu. Such nomenclature opens the door to discriminatory practices.

Now we are just using Greek letters for SARS-CoV-2 variants, though I fear we will run out very soon! The CDC has a summary of these.

I want to focus on the delta variant which has been the focus of much attention in the lay press. This variant is officially a "variant of concern" and is very much worthy of concern. I don't think it is oversimplifying to focus principally on 3 features of variants. First is transmissibility, or how easily the variant can spread in a population. As the pandemic has evolved, probably the most accurate early sign of transmissibility is how quickly a new strain becomes predominant in a population. The delta variant is striking in its spread, now the most common variant in the UK and soon to achieve that status in the US. It is clearly more contagious than the original strain and early variants.

The second feature is virulence, or whether the variant causes higher rates of severe disease and death. In my opinion, the jury is still out on this for the delta variant. Certainly we have seen appalling severity of disease with this variant in India, but I cannot sort out from the reports how much of this could be due to properties of the virus itself versus healthcare access and other issues.

The third, and perhaps most fearsome to those residing in highly-vaccinated communities, is whether the variant is able to evade host immunity and cause a higher rate of infection in those who have immunity from either natural infection from another SARS-CoV-2 strain or from immunization. In this regard, the delta variant clearly can evade immunity to some extent. Thankfully full vaccination seems to protect from severe disease, but partial vaccination is much less effective. It really causes concern for all those people who skipped the second dose of the Pfizer or Moderna vaccines.

Also remember that every person who is infected with SARS-CoV-2 represents a new opportunity for new variants to appear.

Myocarditis and COVID-19 Vaccines

We must be certain that these new vaccines are safe, and in particular that the risk/benefit ratio is favorable. This is especially important for children where, although severe COVID-19 and MIS-C cases occur, the rates are much lower for complications than for adults.

The CDC had planned an update on myocarditis cases associated with COVID-19 disease for June 18, but this was postponed for a week due to the new Juneteenth national holiday. Now it is to be incorporated into the regular meeting of the ACIP scheduled for June 23-25.

However, based on the data that have been released so far, it does seem increasingly plausible that one or more of the COVID-19 vaccines can cause myocarditis. They are still so rare that it is difficult to be certain that it is happening above the expected rate of myocarditis from other causes in the population. It is unlikely to be anywhere near as common as the rates of myocarditis from natural SARS-CoV-2 infection and thus at this time suggests a clear benefit from vaccination. If you're interested, check out a nice study of COVID-19 myocarditis in Big 10 conference athletes.

Stay safe and enjoy the summer!

Tag: myocarditis