Synbiotics?

I'm only mildly ashamed to admit that when I saw a recent publication of a randomized controlled trial of symbiotic therapy for post-acute COVID-19 syndrome (PACS), I had no idea what the term meant. Now I know more, and the study brings up some intriguing thoughts but no direct answers.

First, let's talk about a couple other issues.

Winter Respiratory Illness Season

I'm inventing a new acronym, WRIS, just because I can. CDC went so far as to issue a Health Alert Network posting reminding all of us about the low vaccination rates for covid, influenza, and RSV as well as the availability of treatments for the first 2 infections. So far, flu vaccine coverage in the pediatric age range (6 months to 17 years) is about 36%, pretty poor. The post has a lot of good information throughout, but if you're pressed for time please at least take a look at Table 2 with its links for suggestions for discussions with the unimmunized.

Looking at CDC's weekly viral report page, respiratory illnesses continue to increase. Nationally, emergency department visits for WRIS continue to rise, driven largely by influenza. RSV may be past its peak.

RSV hospitalizations might be coming down, though the data are preliminary:

Influenza-like illness remains high in many states in the South:

Lastly, covid is till out there with high levels in wastewater suggesting we'll see a bigger bump in illness soon.

Although I've presented the national picture, be aware that many of these sites have the ability to display findings by state and other jurisdictions, so you can see what's going on in your area.

Is Pediatric Omicron Infection More Contagious Than We Thought?

That's certainly the implication of a recent study looking at duration of viral shedding in infected children over a 90-day period in early 2022. It's important to note that the study looked only at duration of positivity of PCR at high levels thought to link to infectivity, and also at rapid antigen test (RAT) positivity over time. So, it wasn't a direct measure of whether these children actually transmitted infection at home or in school. With this caveat in mind, they found that 25% of children still had presumed infectious viral loads by day 7 of illness, a bit longer than guidelines recommend for isolation. RAT positivity was a mixed bag as usual (the watermark in the graph just denotes "accepted manuscript" as this paper was published for early online access).

This article shouldn't change practice per se. Looking back at publications of covid spread from children, the results are highly variable with some studies suggesting children have little role in spread. With this much variation in study results, likely the issue is multifactorial, making it difficult to come to any broad generalizations that apply across ages, settings, and time.

Meningococcal B Vaccine and Shared Clinical Decision Making

A few weeks ago I mentioned that healthcare providers don't have enough information at their fingertips to allow parents and patients to truly participate in decisions about vaccination. A new publication about meningococcal serogroup B disease rates helps inform the discussion for meningococcal B vaccine. As you may recall, the ACIP and AAP recently updated meningococcal B vaccination information with the approval of a new pentavalent vaccine. Meningococcal B disease in the US is relatively rare, making risks pretty low overall regardless of vaccination status.

The authors looked at rates of meningococcal disease in persons 18-24 years of age in the years 2014-2017, so not altered by any pandemic considerations. They found 229 confirmed or probable meningococcal disease reports, for an overall rate of 0.18 per 100,000 person years. 120 of the 226 cases for which they had college status were undergraduates, the group at highest risk of meningococcal B infection in the US and the main target for any vaccine intervention. Of those 120 students, 89 had infection with serogroup B.

Students attending 2-year colleges did not have an increased risk of infection compared to non-college students. Only 4-year college attendees had increased risk, and the risk was higher among first-year students and among "Greek life" participants, probably because those groups have a bit more crowding and sharing of beverages, etc.

The authors had some excellent advice in their discussion:

"These findings might be useful for patients, parents, and clinicians when discussing whether to vaccinate adolescents against serogroup B before they go to college. Adolescents planning to live on campus at a 4-year college, particularly ones planning to engage in Greek life or attend schools known for their social life, may benefit more from vaccination. Immunity from MenB vaccines is known to wane quickly, but concentration of risk among first year college students means there is an opportunity to prevent relatively more disease by vaccinating students shortly before they go to college so that the timing of maximum protection overlaps with the highest period of risk."

"Requiring or recommending vaccination against serogroup B disease might not be a tenable policy decision for all colleges, but our findings suggest that 4-year colleges with large numbers of students participating in Greek life or with a high party school ranking might be most likely to benefit from such policies, as these schools were significantly more likely to experience serogroup B cases or outbreaks."

Did you catch that party school mention? Another aid for parents referenced in the study was a ranking of party schools. Those with high rankings presumably represent higher risk for meningococcal B disease. No surprise to me, my undergraduate school didn't make the list.

What I really wanted to know was the Number Needed to Vaccinate (NNV), i.e. how many students would need to be vaccinated to prevent 1 additional case of meningococcal B disease. I knew it would be high because this is such a rare event. It took a little work because I needed a denominator - I knew the number of cases, but I didn't know how many were in the risk group. I had to go to a supplementary table in the article, then look at web links to try to choose a reasonable denominator. I settled on the number of full-time students in undergraduate schools in 2017; it included both 2-year and 4-year colleges. That number, from the National Center for Education Statistics, was 12,085,000. Let's assume the MenB vaccines are 100% effective (they are not, but all are pretty close and I got tired of calculations) and that none of those 89 students in the study were vaccinated (the authors couldn't determine precisely the vaccination rates in their study). NNV is the reciprocal of the absolute risk reduction, which is the rate of infection in the control group (89/12,085,000) minus the rate in the experimental (vaccine) group, which we are assuming to be zero. Crunching those numbers gives us an NNV of 135,786. That is to say, we would need to vaccinate that number of students entering full-time college with a meningococcal B vaccine to prevent 1 additional infection. That NNV number is astronomical and orders of magnitude above NNV for other recommended vaccines. If we were doing a cost-benefit analysis of meningococcal B vaccine, it wouldn't jive at all, but what isn't taken into account is the panic that develops when a case of meningococcal disease occurs on a college campus. Also, I made a lot of assumptions in coming to that number, so it's really just a very rough ballpark. Any decision would need to balance vaccine risks (virtually zero; anaphylaxis from vaccination found 33 cases in 25,173,965 vaccination events in one study, a similar ballpark to the rate of meningococcal B disease above.) This all goes to show that using absolute risk reduction can be more informative than looking at relative risks, which are ratios. For example, in the meningococcal B rates study, participation in Greek life carried a 9.8-fold increase in infection risk compared to other students - a high number that doesn't convey the extremely low infection rates. News stories invariably talk about relative risks rather than absolute risks - bigger numbers sell more papers/advertisements.

So, you can see why those quoted discussion points from the authors are so important. If a parent/potential college student asked me about meningococcal B vaccine, I'd start with saying meningococcal disease is very rare but also very dangerous, with a high fatality rate if one is infected. The risk of getting the infection is very low, about equal to risk of having a life-threatening allergic reaction to any vaccine, both being very rare. [The provider could insert in here if they've ever seen in case of anaphylaxis with a vaccine.] If the plan is to attend a 4-year college, live in a dormitory or fraternity/sorority, and have an active "party" life, the risks for infection are higher though still rare. Some people might value having some more piece of mind and choose to receive vaccination; others may not. Regardless, if at school one hears that you have been exposed to someone with meningococcal infection, you need to follow specific guidance from the local health department or student health team without delay - antibiotic and/or vaccination might be life-saving.

What I Learned About Synbiotics

I'm exhausted after too much number crunching, let's look at a new study that certainly is food (pun intended) for thought. A few definitions first:

Prebiotic - a nondigestible food ingredient that promotes the growth of beneficial microorganisms in the gut

Probiotic - live microorganisms ingested to improve the gut microbiome

Synbiotic - a combination of prebiotic and probiotic substances

The randomized, double-blind, placebo-controlled study looked at 463 adult patients in Hong Kong who were previously diagnosed with covid and fulfilled a standard definition of PACS. The experimental group received twice daily oral doses ("sachets") consisting of 3 probiotic bacteria and 3 prebiotic compounds; the control group received vitamin C with inert additives such that the packets of oral doses were identical in appearance, smell, and weight. The choice of synbiotic elements was based specifically on prior Hong Kong microbiome studies that suggested beneficial elements. The main outcome of interest was change in PACS symptoms at 6 months.

Although there was no difference in quality of life or physical activity between the 2 groups, the treatment did seem to have a beneficial effect on several symptoms and was correlated with favorable microbiome changes.

Maybe some progress, we'll need to see more studies on synbiotic therapy for long covid, hopefully expanded to many different populations. I think I'll go get some yogurt for lunch.