My recent bedtime reading included a mystery by Ruth Rendell, a much-acclaimed British mystery writer. A dog with a name out of Greek mythology appeared in this one, and I was convinced it was a clue to the murderer's identity. Of course it wasn't.
Pediatric Influenza Vaccine Effectiveness (VE)
This study from CDC and its flu VE partners appeared online this week. It provides a good overview of flu VE over 9 flu seasons plus raises some interesting questions. Investigators analyzed data from active flu surveillance at 5 sites around the country (Michigan, Pennsylvania, Texas, Washington, and Wisconsin), the same data that CDC uses to report flu VE every year. None of the numbers are new, but looking at trends and associations over the years was interesting. Note these numbers are from active surveillance rather than collecting data from passive reporting systems like administrative databases; it is much more accurate. Because it is based in outpatient sentinel sites it specifically gives us VE for medically-attended outpatient respiratory illness.
In Figure 1 below the overall VE was 46% - that may not sound that great, but remember this is VE against medically-attended illness, not digging deeper to hospitalization rates which are very high. As you can see, VE varied somewhat with age (younger kids a little bit better effectiveness) and with flu strain.
Influenza A(H3N2) viruses cause more severe illnesses generally and also have had lower VE rates. Figure 2 looks at seasons where H3N2 was the predominant circulating strain and categorizes them as to whether the vaccine that year was either well-matched or mismatched for the strain that was circulating. The advantage for the younger children is more evident in some of these comparisons, especially for the mismatched 2014-15 season.
Why did the 6 to 59 month-old age group show better VE? The authors offer some speculation, including age-related differences in immune response to other factors such as social interactions or characteristics of families with young children that might further protect from infection and doctor visits. Whether this is a difference in immunity or behavior, or a combination, further studies looking into these factors can help inform future preventive measures.
Variants and MIS-C
A group of Kawasaki Disease investigators from several different institutions reported rates of MIS-C categorized by SARS CoV-2 variant periods. Dr. Ashraf Harahsheh, a cardiologist at Children's National Hospital, is a co-author. I had no involvement in the study except as 1 of perhaps a few hundred or so clinicians who helped care for these children at Children's National.
The Table below is a good summary.
Note that the coronary artery row describes dilatation, different from aneurysms. It is certainly reassuring that disease severity declined somewhat during this period, but severe disease still occurred. The declining relative risks of ICU admission from the alpha to omicron eras might be due in part to more comfort of clinicians managing these cases, though that wouldn't explain the concomitant decrease in shock over the same period. One hopes that further study of these patients will lead to discovery of better management for both Kawasaki Disease and MISC-C.
Can Post-Covid Illness Be Prevented?
A couple of studies in adults looked at factors associated with post-covid illness. One investigation was performed in the VA system on a cohort of almost 300,00 individuals. After correcting for many potentially confounding variables, treatment with nirmatrelvir (combined with ritonavir as Paxlovid) did appear to lower risk of persisting illness.
This was a statistically complicated but excellent study. However, what I still hope to see is some post-covid illness study that effectively separates conditions due to direct end-organ damage from the virus versus the fatigue/malaise/dysautonomia/brain fog symptoms. Does an intervention prevent those complications in patients who do not have end-organ damage?
The other study was a systematic review and meta-analysis of 41 studies to identify risk factors for post-covid conditions. They identified female sex, older age (looking only at 18 years and older), higher BMI, and smoking as significant risk factors.
Neither of these studies included pediatric subjects, but still they shed a little more light on this confusing hodgepodge of illnesses. I hope for some tangible breakthroughs in the coming years.
Detective Stories
Much of medical practice, and maybe especially infectious diseases practice, requires good detective work including being observant and asking the right questions. I love Rendell's books. Her characters are often quoting British literature and historical events that I enjoy looking up, but I clearly chased the wrong clues this past week and totally misidentified the perpetrator. I'll keep practicing.
Color me confused … there were very few pediatric cases of illness linked to the ancestral strain , and the first case reports of MIS-C only arose weeks after the beginning of alpha strain surge ( correct me of that is wrong )
I am quite surprised the national incidence of MIS-C is so close between the ancestral /alpha/delta and Omicron era
It was my understanding that the experience of our pediatric hospital - no suspected MIS-C related to ancestral , some with alpha surge , lots with delta surge , much less with Omicron was the general experience
Is what I just described consistent with the Children’s National experience or more consistent with the day reported in this report ( as it is in a letter in NEJM , data is not really explained in detail )
Thanks for this question Michael. I can reply via personal anecdote for this, plus it gives me a chance to explain a bit more about this study.
I remember very distinctly I was the attending physician on the inpatient service at Children's National in April 2020, and one morning I read a report from one of my many alert feeds that a group in London had described a new entity they called PIMS: Paediatric Inflammatory Multisystem Syndrome. I was skeptical - we had seen plenty of covid infections in kids by then, and this didn't match with anything in our experience. Later that afternoon I saw a child in the hospital who fit the description perfectly. By that evening I was on the phone with our division chief Roberta DeBiasi and with Jane Burns, a pediatric infectious diseases physician at UC San Diego who had a long interest in Kawasaki Disease and some knowledge of the European cases. We cobbled together a management plan that of course was modified as we gained more experience. So, this was definitely well before we experienced SARS CoV2 variants.
Also, note that most MIS-C patients have negative PCRs for the virus because the infection itself is long gone by the time MIS-C appears. This makes it difficult to know what variant might have been the inciting strain for a particular episode of MIS-C. For the study, the investigators used an established method to assess timing of variants in the country of origin of each child, so perhaps more of a ballpark idea of variant assignment.