COVID-19 – Page 8 – Pediatric Infection Connection

Yet Another Game Changer

Bud WiedermannFebruary 27, 2022Leave a comment

The CDC appears to have answered my question in last week's post, at least partially. While we are by no means in the clear, the new transmission prevention guidelines signal a more logical approach to NPIs (non-pharmaceutical interventions) that fits the current stage of the pandemic. On the other hand, we did see some controversy about whether the CDC is purposely withholding data from the public.

Is the New Guidance Too Confusing?

The guidance for specific areas depends on both disease activity and healthcare capacity for that region which makes a lot of sense because we know we won't reach herd immunity. Prevention of severe disease, death, and healthcare rationing are primary goals. We've seen healthcare taxed beyond capacity trying to care for both COVID-19 patients as well as all the other population health needs. CDC has set up a site that gives a specific answer for a community's level of risk (high, medium, or low) and corresponding advice. Just look at the color of your area of interest in their map and you will have the quick answer.

Getting to the underlying data for the categorization is a little harder but not terribly imposing. For example, if you wanted to know what's going on in Montgomery County, MD, you'd see that as of February 27, 2022, community transmission is "substantial" with the case rate at 66/100,000 and percent of positive tests at 1.83%. 4.43% of inpatient beds and 8.42% of staffed ICU beds are occupied by COVID-19 positive patients. What this all means, going back to the main site link, is that Montgomery County is in the Low community risk level.

I am most interested to see what happens in those jurisdictions where states have made pre-emptive rulings about NPIs that may contradict CDC's guidance. How many of them will toe the new line? Also, will citizens comply when their community experiences an increase in risk and should increase precautions?

Transparency is Essential

I don't have a problem with CDC or other agencies not releasing data that could be inaccurate, but I do have a problem with withholding information because someone might misinterpret the data. Just as with any scientific study, the investigators are obligated to discuss what the results mean and the limitations of the study.

Let's look at the example of wastewater testing and compare the US to the UK. Wastewater testing can be extremely valuable for tracking disease hotspots and also for tracking variants. CDC reports 15-day data on their website. You can see trends and activity in different parts of the country, though I couldn't find any information about variant tracking.

The UK, on the other hand, offers much more extensive information about wastewater tracking in monthly reports, including variant percentages across the country. The country coverage is much more extensive than in the US, though I didn't see any data from Wales.

Here is a screenshot of sites covered by wastewater tracking in the US. Large swaths of the country are not represented:

Dots represent data collection sites, with colors showing percent change. Red is bad, dark blue good, other shades in between, and gray with no recent data.

In general I wouldn't worry as much about misinterpretation of CDC data as I would about deliberate misuse of data. An example of the latter has been an ongoing problem with use of the Vaccine Adverse Events Reporting System (VAERS) data during the pandemic. Virtually every pediatric healthcare provider knew well before the pandemic that VAERS could not provide information about causation - anyone can report any type of event as being associated with a vaccine, and the reports are publicly available. That didn't stop many bad actors from using the data to falsely support claims of harm from COVID-19 vaccines.

In the Clear?

Bud WiedermannFebruary 20, 2022Leave a comment

I must admit a bit of surprise that so many "blue" states are relaxing NPIs (Non-Pharmaceutical Interventions) for the pandemic at a time when new case rates, while falling, are still quite high. Is this all too soon? Too late?

What Do the Models Predict?

Most of us don't have the mathematical background to critique the various pandemic models, but let's look a little closer at one of them. The Institute for Health Metrics and Evaluation (IHME) is an independent population health research organization based at the University of Washington. IHME was founded in 2007 and is one of my favorite sources for data and forecasting during the pandemic.

Let's look at their most recent data compiled February 17. This is a link I'd really encourage you to explore because as you will see the graphs are interactive. Although I've set the link to open for the view of the United States, you can search anywhere.

It's important to look at several different outcomes, especially in the omicron era, to get an accurate picture. We have lots of variability in healthcare seeking and testing behavior, plus as my wife reminded me most of those rapid home test results don't get reported to any public health authority. However, hospitalization rates are a reasonable assessment of what's going on plus focus on an outcome that we care about most. Here's a screen shot of IHME's current projection for hospital bed use in the US.

This is certainly encouraging, though projections will depend on what future variants have in store for us.

Variant Alphabet Soup

Writing in the BMJ, journalist Elisabeth Mahase reminds us that the World Health Organization first designated omicron a variant of concern on November 26, 2021. A lot has happened in the last 3 months. In Pango-speak (Phylogenetic Assignment of Named Global Outbreak lineages, a software tool) it is designated B.1.1.529.1, now BA.1 for short. It accounts for >90% of cases globally currently, including in the US. BA.1 seems to have increased transmissibility but lower severity, although as we've seen it can still stretch our healthcare resources beyond capacity. It exhibits immune escape in terms of infection, though vaccine and natural immunity still provide good to excellent protection against severe disease, depending on individual circumstances.

The subvariant BA.2 (B.1.1.529.2) is a bit in the spotlight now, comprising a few percent of US cases as we hold our breath to see if it precipitates another infection wave. BA.2 certainly has a faster replication rate than BA.1 and likely is more transmissible. Although cases have been reported throughout the world, it's still a bit early to judge relative severity.

BA.3 is much less common so far. Its spike protein mutations aren't that different from BA.1 and BA.2; much remains to be learned about its ability to spread and cause severe disease.

NPI relaxation across the US leads us into a new era of the pandemic. We'll see what this experiment reveals in the coming months.

Two Years and Counting

Bud WiedermannJanuary 9, 2022Leave a comment

This is exactly my second COVID-19 anniversary. I wouldn't have realized that without one of our infectious diseases fellows mentioning an email I had sent out near the start of this whole thing. I had no recollection of that but was able to search through my Sent box and found it. It was dated January 9, 2020, and basically said to keep a watch on this new coronavirus thing in China, but at least it didn't appear to be showing human-to-human transmission. How times have changed.

A lot has happened in the past week, and most of that you've probably already heard about. Stick to the CDC website as a primary resource. Today I'll focus on just one COVID-19 topic to direct you to new publications you may not have seen, plus detour with news about an unrelated infection.

Testing for SARS-CoV-2

This is getting more confusing with possible less sensitivity for omicron with some of the rapid antigen tests. I first want to mention a review article published this week that I strongly encourage all healthcare providers to read. It's available free without journal subscription. I realized while reading it that the information answers virtually all of the questions I receive from practitioners about testing. It also has great figures and tables.

Somewhat along the same lines is some new information about false positive rapid antigen testing, very helpful though it is based in pre-omicron times. Usually when we talk about rapid antigen tests we are more worried about false negatives, but false positives do occur usually at a low rate. The two take-home points from this article are that 1) if rates of disease are really low in a population (not the case now!) then at some point no matter how high the test specificity a positive test is more likely to be false than true; and 2) sometimes test errors occur due to a faulty batch of test kits.

I do think we'll get over this omicron hump eventually and back to a time when infection rates are low. We all need to keep pushing on until we get there. Thanks to all the healthcare providers who are working so hard to keep our kids safe.

A Bad Year for Rabies

Rabies infection is about as close to 100% fatal as one can get with any specific diagnosis. CDC just reported on 3 rabies cases, 2 adults and 1 child, in the US resulting from separate bat exposures in August 2021. All 3 had direct contact with bats, either bite or collision. All became ill within 3-7 weeks and died 2-3 weeks after symptom onset.

Worse than that are a couple of details about the individual cases. Two didn't realize they were at risk for rabies and did not seek care until they developed symptoms. The third was even more sad: the patient submitted the bat for testing, it tested positive, but the patient refused post-exposure prophylaxis because of "a long-standing fear of vaccines." I wonder how much the current vaccine hesitancy associated with COVID-19 influenced that decision.

These cases also serve to remind us we can't turn all of our attention to COVID-19. With such a great strain on healthcare providers and epidemiologic systems it is likely easier to overlook something new coming up, sort of like those few cases seeming to originate from an obscure market in China.

Hang In There

Bud WiedermannDecember 26, 2021Leave a comment

No point in sugar-coating, things are likely to get worse before they get better. The news is disappointing, but we can at least hope that omicron and influenza will crest quickly and recede somewhat.

Omicron is Different

Yes, you already knew that. We certainly know it is (much) more highly transmissible but we still don't have enough data to know if severity is different. Full vaccination (primary series plus booster) is likely to be helpful against severe illness though much less so against infection itself.

Our most commonly available monoclonal antibody regimens are unlikely to be effective against omicron; at Children's National we have paused offering both the bamlanivimab/etesevimab and casinivimab/imdevimab monoclonal cocktails given the high rate of omicron in our region. Sotrovimab should be effective against omicron, but currently we don't have this agent on hand and availability is likely to be limited for the next few weeks. Note that use is limited to outpatients 12 years of age and older and weight 40 kg and greater with positive SARS-CoV-2 testing and high risk for hospitalization or death.

We now have emergency use authorization for 2 oral medications, molnupiravir and nirmatrelvir/ritonavir (Paxlovid), for treatment of mild-to-moderate COVID-19 illness. Paxlovid, consisting of 2 viral protease inhibitors, is authorized down to the 12 years of age/40 kg weight category with high risk for disease progression. Note that Paxlovid is a CYP3A inhibitor, so beware of drug interactions. Molnupiravir is less effective but can be used in adults at high risk for progression who cannot access or receive other treatment options. In the coming weeks molnupiravir is likely to be more available than Paxlovid, but note that it should not be given to children - concerns for joint problems in juvenile animals likely will delay pediatric trials. Because it is a mutagenic agent, use in pregnancy is an unknown risk and patients of reproductive age should use methods to prevent pregnancy while taking the medication and for either 4 days after (females) or 3 months after (males) the 5-day treatment course.

Another difference for omicron is that some SARS-CoV-2 tests may show false negative results. It is a little tough to keep track of new information about this, but the FDA has a great resource.

Influenza on the Rise

Influenza has been creeping up nationally and also at Children's National Hospital, though at the hospital it has not yet reached numbers that we associate with the official start of flu season. Now a preprint study suggests that the 2021-22 influenza vaccine has reduced ability to inhibit replication of the H3N2 clade most likely to be circulating this year. That could mean an antigenic mismatch for this flu season, but we won't have an estimate of that for at least a few months. Even if this is true, influenza vaccination is still very important and I would encourage everyone to be immunized - it's not too late.

Hello Flu Season

Bud WiedermannDecember 5, 2021Leave a comment

I'm sorry to disappoint those of you expecting an omicron variant update this week. Although we've seen a lot of commentary in the lay press and some preliminary reports from around the world, in fact we still don't have anything substantive to answer our outstanding questions about transmissibility, disease severity, and immune evasion. Maybe next week.

Home for the Holidays with Flu?

At Children's National for the week ending November 28 we had a slight uptick in influenza cases, though not enough to declare our official start of flu season. CDC surveillance suggests the beginning of increases nationally. Conveniently the CDC published a detailed account of a what has been reported across the country: flu outbreaks on college campuses. The December 3 MMWR report was of an outbreak on the University of Michigan campus occurring in October and November. All the isolates were influenza A H3N2 and should be covered by this year's vaccine. However, H3N2 is a bit more troublesome than other strains in that it is more prone to drift as the season progresses. It is somewhat concerning that individuals with positive and negative tests for flu had similar vaccination rates, suggesting not great protection against mild infection, at least in this one relatively small outbreak. Watch out for spikes in flu following holidays as college students and other travelers add fuel to flu season.

COVID-19 Monoclonal Antibody Use in Young Children?

I was caught completely unaware when I learned on December 3 the FDA extended emergency use authorization down to the newborn period for the monoclonal antibody combination of bamlanivimab and etesevimab for children at high risk of developing COVID-19 complications. Previously this combination had EUA only for high risk individuals 12 years and above with weight at least 40 kg. This extension was based on some new data from an open-label (i.e. no control arm) trial looking at treatment effects on viral load as well as some pharmacokinetic data on weight-based dosing for younger age groups. The EUA covers both therapeutic and post-exposure indications. Note also that, for children above age 2 years of age, this is only for outpatient use.

I have one main concern about this EUA related to use in children in the first year of life. First, the notice lists age < 1 year as defining a high risk group, without need for any other risk factors. To my knowledge no study has found this age group to represent high risk for COVID-19 complications. Second, the youngest child in the trial was 10 months and weighed 8.6 kg; only 5 children in the trial were less than 2 years of age. We know that metabolism in newborns and young infants is very different from older children and, coupled with the fact that I can't find evidence that otherwise healthy young infants represent a high risk group, I'm reluctant to sign on to use in otherwise healthy children in the first year of life. Our team at Children's National is looking at the data and will come up with guidelines incorporating this new EUA.

Tag: COVID-19