I love to read. However, I've got a long ways to go to match comedian Mel Brooks's literary appetite. In a recent NY Times interview (sorry, subscription only), his past reading list is prolific. I suppose he could be exaggerating to pull our collective legs, but I doubt it.
Compared to the previous week, it wasn't difficult to find new articles to talk about this week. I'll just pick a few.
A mAb-Less Winter
I stole this phrase from Dr. William Werbel, an adult infectious diseases physician and researcher at Johns Hopkins, speaking at a CDC/IDSA Clinician Call webinar on November 12. It's a great sound bite of how variants are changing our prophylactic and therapeutic landscape for COVID-19 particularly with regard to use of monoclonal antibody products.
It's getting tough to keep track of all the variants going around, but keep in mind we are seeing exclusively omicron subvariants. We haven't had a major change in variant type since omicron appeared almost a year ago. Here's the latest picture from the CDC:
What you can see most recently is the decrease in proportion of BA.5 accompanied mainly by increases in BQ.1, BQ.1.1, and a little of BF.7. It's still a bit early to understand all of the clinical implications of these newer sublineages, but the main concern is that they appear to have specific mutations that limit the effectiveness of current monoclonal antibody preparations we have come to rely upon.
Bebtelovimab is the only monoclonal antibody effective for treatment currently, but laboratory studies strongly suggest that it loses significant potency with mutations in the 444 region; BQ.1 and BQ.1.1 have the K444T mutation. Similarly, Evusheld (combination of tixagevimab and cilgavimab) is an important agent for prophylaxis of SARS-CoV-2 infection, long-acting and widely recommended (though underutilized) for individuals with immune compromise. Evusheld loses potency against viruses with mutations in either the 444 or 346 regions. BQ.1 has the K444T mutation only, BF.7 has the R346T mutation only, and BQ.1.1 has both mutations, Together, these 3 subvariants comprise over half of the circulating viruses in the US and are rising. Thus the concern that this winter will leave us stranded without effective monoclonal antibody products for treatment and prevention. Of course research is ongoing to develop new monoclonal antibody preparations, and we still have antiviral agents like ritonavir-boosted nirmatrelvir (Paxlovid), remdesivir (Veklury), and molnupiravir (Lagevrio) that appear to retain activity against new subvariants.
For the most part, monoclonal antibodies exert their effects by providing neutralizing antibody against the viruses. However, vaccines go a bit further to stimulate not only neutralizing antibody production in the recipient but also to activate other parts of the immune system to lower risks of infection and severe disease. I'll play the broken record again: everyone eligible should be vaccinated and boosted against COVID-19.
Covid and Kids
Two recent reports of covid and young children are helpful. One, from the CDC, was widely publicized. The other, from the UK, was not, at least not in the US that I could appreciate. Whenever I see data drawn from administrative databases I worry about drawing too many conclusions, because clinical details often are lacking or inaccurate. However, we do have some more refined clinical details in both of these studies.
The CDC report focuses on infants under 6 months of age during the time period June 2021 through August 2022 (first half mostly delta variant, second half omicron). What struck me most were the risk factors for hospitalization which did not change during the study period. Overall almost a quarter of all hospitalized infants had at least one risk factor for severe disease, with prematurity being most common. The proportion of infants with risk factors generally increased with age. This is clearly an alarm to promote immunization of pregnant people to protect not only themselves but their infants as well.
The UK study looked at deaths in children and young adults less than 20 years of age; having a national health system makes this data collection much more accurate than we can provide in the US. Over 13 million individuals comprise this UK age group, and the investigators identified almost 3 million covid infections during the study period of March 2020 through December 2021 (almost all pre-omicron). They found 185 deaths within 100 days of a positive SARS-CoV-2 test and then dug deeper with clinical questionnaires. Ultimately they concluded that 81 of the deaths were caused by covid with the remainder attributed to other causes. With this small number it's tough to break this down further, but about half of the non-covid death subjects had no comorbidities compared to about a quarter of the covid deaths. Within the covid death group, severe neurodisability was particularly striking to me at about one-third of that group. Note that during the study time period, covid vaccines were not available to the under 12-year-old population.
School Masking Works
This might be a case of closing the barn door after the horses have escaped, but we now have further evidence that masking works. The study from multiple institutions in Boston looked at covid incidence before and after school masking mandates were lifted and, although this was an observational study rather than a prospective randomized trial, it did confirm that masking can help prevent infection and illness. This should be useful should we encounter a severe upswing in covid cases in the future; masking could mitigate students missing school. Another important feature of this article is that schools with poor ventilation and higher rates of students with language barriers, disabilities, and low-income families are at highest risk of infection. The discussion portion of the article should be required reading for school administrators and policy experts.
My Homework Just Increased
But back to Mel Brooks, one of my all-time favorite entertainers and personalities. In the Times interview, he mentioned over 20 books/authors, plus 9 pieces of music and 4 entertainers, in a wide-ranging commentary on life influences. I think my reading list just doubled. I was totally taken aback when, asked about the best book he ever received as a gift, he mentioned Gogol's "Dead Souls" as a "life-changing gift" that he reads annually. I'll be searching for a copy in my area used bookstores.