omicron variant – Page 11 – Pediatric Infection Connection

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.

Roller Coaster Week

Bud WiedermannFebruary 13, 2022Leave a comment

I guess we all should be accustomed to the ups and downs of the pandemic. We continue to see good news with waning of the omicron surge around the world, but parents of children under 5 had a bit of a jolt on Friday with the news that the Pfizer vaccine will not be discussed by the FDA next week as originally planned. We now await ongoing data from the trial which has begun a booster dosing phase. Regular readers of Pediatric Infection Connection will know that I oversee this trial at Children's National Hospital, but I have no knowledge of the data submitted by Pfizer to the FDA so can't provide any independent opinion.

Booster News?

Speaking of boosters, CDC released some important new information about boosters, some of which pertains to children. First, an early release in MMWR highlighted waning of effectiveness of 2- and 3-dose mRNA vaccines. This is sort of a glass half empty or full view, I was actually more encouraged by the continuing effectiveness, particularly for boosted individuals, against severe disease and hospitalization. Just looking specifically at the data from the omicron-dominant time period, vaccine efficacy (VE) in preventing emergency or urgent care visits was 87% 2 months following a third or booster dose though dropped to 66% beyond 5 months (note few data available for this latter estimate). VE in preventing hospitalization was 91% and 78% for those 2 intervals post third dose. This is by no means the final word, lots of limitations in this study and also it looked only at individuals 18 years of age and older and did include a significant number of people with immunocompromise and other risk factors for severe COVID-19 disease. No information about how these risk factors specifically affected VE.

Also, as promised the CDC issued an update to guidance for vaccination of those with moderate or severe immunocompromise to include a fourth dose in some circumstances. This update applies to people down to 12 years of age and provides a good road map for vaccination of those individuals.

Variant Viewing

I'd definitely be happier stargazing or watching butterflies and bees in season, but lately I've been keeping an eye on the BA.2 subvariant of omicron. It has started to appear in our CDC data (after clicking on this link, choose Variants and Genomic Surveillance, then Variant Proportions from the left-side menu). BA.2 now comprises 3.6% of isolates as of Feb 5 compared to 96.4% omicron BA.1) and similarly has increased slightly in the UK. As I indicated last week, it is more transmissible than the original omicron variant, but it isn't clear whether prior infection with omicron BA.1 confers some immunity against BA.2. That is probably the key factor in determining if we will see another surge due to BA.2.

I also note some encouraging news in the UK that the reproductive number is now estimated at 0.8 to 1.0, a milestone that signals flattening or decrease in the pandemic. Of course it could be just another ride on the roller coaster but I choose to take this as a further good sign.

6 More Weeks of Winter

Bud WiedermannFebruary 6, 2022Leave a comment

Apparently Punxsutawney Phil saw his shadow this week, but maybe you didn't know about this important groundhog connection to the world of infectious diseases. Woodchucks (aka groundhogs) are affected by WHV (woodchuck hepatitis virus) and have been used in hepatitis B research. Unfortunately, Phil's forecasting accuracy rate for winter weather duration of 40% might be better than most models of COVID-19 future waves.

Important Conversations at ACIP

I didn't see much about this in the lay press, but the Advisory Committee on Immunization Practices met on February 4, primarily to discuss the recent FDA approval for the Moderna mRNA vaccine that will now be marketed as Spikevax. That all went fine, but I was more interested in the afternoon discussions.

Tracking of vaccine-associated myocarditis continues with further data from both the US and international sites. Although there are no large randomized controlled trials directly comparing the 2 mRNA vaccines, it seems likely that this risk is slightly higher with the Moderna vaccine than with Pfizer's. However, both risk rates are considerably lower in comparison to the risk of myocarditis from natural infection. I think the best way to use this information might be to advise a male adolescent or young adult, the highest myocarditis risk group, to choose the Pfizer vaccine when starting a primary series or considering a booster. The vaccine-associated myocarditis still seems to be very mild with no long-lasting sequelae, but well-designed long term follow-up studies are ongoing.
The other discussion I found very interesting was regarding the interval between first and second doses for a primary mRNA vaccine series. Canada and other countries now have a fair amount of data on this; in the US this has not been well-studied, and in the initial vaccine research trials virtually all of the participants had second doses at around 3 (for Pfizer) or 4 (for Moderna) weeks after the first. Based on the meeting presentations, consensus of ACIP members seemed to lean heavily towards recommending an 8-week interval between the first 2 mRNA vaccine doses, especially in times of low community COVID-19 activity where risk of infection during that more prolonged interval between doses will be less.
Also, stay tuned in the next few days (I think) for more specific and very helpful guidance on immunization of individuals with moderate or severe immunocompromise. This will be very helpful to those patients as well as to providers who advise transplant and other patients on this topic.

Alas, Poor Yorick

I must admit I don't know much about Denmark: it is the origin of the name for epidemic pleurodynia, Bornholm disease, and it is the setting for what is perhaps Shakespeare's best play. Now, Denmark is in the COVID-19 spotlight for 2 reasons.

First, a recent preprint shows us that the new omicron "subvariant," BA.2, has become very prominent in Denmark. The study looked at primary cases of COVID-19 from December 20, 2021, to January 11, 2022, to identify secondary attack rates in those households. Tracking of secondary attack rates ended January 18, and testing of household members was relatively high. From the 8541 primary cases in households, 5702 out of a potential 17,945 exposed household members were infected. When broken down further, the secondary attack rates for BA.1 (the original omicron) and BA.2 were 29% and 39%, respectively. This provides further evidence that BA.2 may be slightly more infectious than BA.1. Vaccination of exposed individuals didn't seem to affect secondary infection rates, but note that this included asymptomatic infections; there was no evidence of increased disease severity of BA.2.

I'm especially interested to watch how this all unfolds in Denmark, both because they are experiencing relatively high percentages of BA.2 and because they have just instituted one of most relaxed mitigation strategies anywhere.

It's hard to guess whether BA.2 has the potential to cause additional new disease surges after BA.1 across the world. Try asking Punxsutawney Phil.

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.

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.

Tag: omicron variant