Pandemic Update for 2022-02-11: Challenge
Items of recent pandemic news: Omicron boosters prove unhelpful; wastewater surveillance comes into its own; Covid-19 causes long-term heart and circulatory issues; results from the first SARS-CoV-2 challenge trial published; and more. Plus two fripperies.
Quote of the week
- Eric Topol — “[This] may be the most impressive Long Covid paper we have seen to date.” [ Regarding a large-scale study of long-term cardiovascular sequelae in veterans. ]
Results from the SARS-CoV-2 challenge trial
Results are finally out, in preprint form, of the challenge trial mounted in the UK beginning a year ago. Thirty-six young, healthy adult volunteers were given a load of viable SARS-CoV-2 virus (the original Wuhan strain) intra-nasally, then watched closely in isolation and tested for 14 days. No one got seriously ill. Here are the top-line findings:
- 53% of volunteers got infected
- Contagiousness started earlier and lasted longer than has been thought
- Virus built first in the throat, then to higher levels in the nose
- PCR turned positive after 40 hours for the throat, 58 hours for the nose
- Lateral-flow antigen tests proved reliable and accurate
The amount of virus placed in noses was calculated (or guesstimated) as the dose that would result in 50%-70% of participants becoming infected. If that level had not been reached, the experimental protocol called for dose escalation until it was. But the researchers guessed right the first time. The crew at This Week in Virology went over the challenge paper in detail and their discussion on how the dose was arrived at may be of interest. Watch just over two minutes beginning at 21:16. The reporter at Technology Review described the dose as approximately the amount of virus that would be present in a single drop of the nasal secretion of an infectious person.
The process the researchers went through to find their 36 volunteers was onerous. The study was originally designed for up to 90 participants. But after fielding interest from an initial 27,000 people, the researchers ended up excluding 99.87% of them for a variety of reasons.
Regardless of how much can be quickly learned from a challenge study, the practice of deliberately infecting people with a potentially deadly agent is not without controversy. Strong opinions can be found on both sides of the question. Read this opinion piece in Stat by an advocate of the practice of challenge trials. Vincent Racaniello, the founder of TWiV, was not shy about voicing his opposition (watch 20 seconds beginning at 8:57). (The other TWiV hosts were keeping their opinions about challenge trials to themselves).
Here is Zvi Mowshowitz, clearly a proponent, on the value that a challenge trial can offer, quickly and for little cost:
Covid-19 and long-term cardiovascular sequelae
We last visited the question of what effect SARS-CoV-2 has on the heart in November, and the subject then was mostly what happens during acute infection. A new study examines long-term cardiovascular consequences, a month to a year after SARS-CoV-2 infection, and the news is not good.
Working with data from 11 million US veterans’ electronic health records, researchers found that up to a year after acute illness, the risk of every cardiac condition they examined was substantially higher for survivors of Covid-19. The increased risk correlated with disease severity. A summary of the research in Science put it this way:
You do not want to get this disease.
How much protection against variant reinfection?
Protection afforded by previous Wuhan-strain infection against subsequent variant infection or severe disease, in %
Suppose you had gone through a case of Covid-19 in 2020, infected by the original Wuhan strain of the virus. Further suppose you had not been vaccinated in the interim. How much protection does the immunity from that original case provide you, in the face of new viral variants?
A study led by researchers at Weill Cornell Medicine – Qatar aims to answer that question (paper; writeup in CIDRAP). I have summarized the results in a chart — click for a larger version. The takeaway: An initial bout with SARS-CoV-2 provides good protection against infection by the earlier three variants, and less so against Omicron (56%). Good protction against severe disease (hospitalization, ICU, death) holds strongly for all variants except Alpha (69.4%).
Wastewater surveillance comes of age
We have been talking for a while about coronavirus surveillance by periodic testing at sewage plants. The CDC has now elevated visibility into this practice by adding a wastewater module to its Covid-19 data tracking dashboard. The agency will be adding sites to the dashboard as they come online in the coming year.
Katelyn Jetelina (Your Local Epidemiologist) has a detailed explainer on wastewater surveillance.
We have been following developments in the story of widespread SARS-CoV-2 in white-tail deer in the US — reportedly in 15 states now. Two pieces of news on that front:
- Minnesota deer — This state has been added to the roster of locations where the coronavirus has been detected in white-tail deer, in a pilot surveillance project led University of Minnesota researchers. The virus does not seem to be as widespread here as in some other states — reportedly up to a third of wild deer are infected in Iowa and Ohio. In Minnesota it’s 6.3%.
- Omicron detected — the first sighting of this Variant of Concern in deer was reported on Staten Island in New York ( preprint; NY Times coverage). Some of the infected animals showed antibodies to earlier variants, indication that they had been reinfected — Omicron seems to evade cervine immune systems as it does humans’.
Omicron’s decline proceeds apace
Just an update from last time when we noted what may have been a momentary pause in the decline of the Omicron wave. If that pause was even real, it is over now. The figure shows the current case acceleration in the 21 states that had shown an uptick last week. Red means still accelerating, blue means slowing. The BA.2 sub-variant accounts for 3.6% of US cases at this point, and is not (so far) affecting the rate of Omicron’s decline.
An Omicron-targeted booster is not helpful
A study (preprint; Stat News coverage) in macaque monkeys led by NIAID’s Vaccine Research Center found that an Omicron-targeted booster shot of the Moderna vaccine showed no advantage over the existing booster dose. The results were similar to those the same group obtained last year when testing a booster targeted at the Beta variant. In both studies, either booster produced B cells and antibodies that were cross-reactive against the original virus and the variant.
Fripperies: Pass the Ball; Wikitrivia
We have two fripperies for you today. One demands only a couple of minutes of your time and the other will soak up hours if you let it.
The first is a delightful video, 2:39 long, created in series by 40 animators around the world. The subject is a red rubber ball and the passing thereof. Each animator added three seconds to the video and passed it on to another artist of his/her choice in a different country.
The second frippery you may have already encountered; it has been viral since the middle of last month. Wikitrivia asks you to order cards representing historical events on a timeline. That’s it. You play until you make a third error, and then your score (“streak”) is one less than the total of right answers up to that point. It starts out easy and gets progressively more difficult as the events become dense on the timeline.
And some of the questions, taken from Wikipedia and Wikidata, are beyond obscure. Did the kingdom of Mauritania get going before the Ottoman sultanate of Murad IV? Was the Massey Ferguson company founded after the Symbolism movement in art? Was Portland cement discovered before or after Aubrey Beardsley was born?
Taking a page from Wordle, after each game Wikitrivia generates a cryptic score for you to post on social media.
The Wikitrivia project is hosted on Github by its developer, Tom J. Watson, and this page collects suggestions for game cards that are in error — this can happen in a game based on data that is editable by anyone in the world. I have added two cards to that list.
My longest streak so far is 17. Beat it if you can and drop a comment below.
Very interesting human SARS-CoV-2 challenge study. I’m slightly curious as to what their acceptance criteria were to exclude over 99% of study volunteers. Wow! Also, seeing Eric Topol’s being quoted brought back a rush of memories to me. Eric was a participant in several CV programs I put together back in the late 80s and early 90s during meetings of the American College of Cardiology and the Heart Association. I was a regional Clinical Liaison for the old Dupont Pharmaceuticals, and worked closely with cardiology thought-leaders in presenting programs on several of our CV products. He was a pretty cool guy who loved expensive wine! He also “sold” a lot of drug for us. 😁 So. good to see him getting out front with this issue.
Eric Topol is one of a handful (well, maybe several dozen) of experts who gets quoted all the time in the popular media on pandemic subjects. As to the challenge study’s exclusion criteria: I made a copy of the decision flowchart from their paper. Click on the thumbnail here to open it in a new window.
Lazy me! I never looked further than the abstract on that study. However, looking at the flow chart, it appears that the 27,000 “candidates” is a false population. The 36 selected — 32 actually followed — was the true population. In reality, that’s way too small (I feel) to develop any reasonable clinical conclusions or extrapolations to the general population.
Interestingly enough, two years after I did my final CV program for Dupont, I totally changed careers, transitioning rapidly from medical marketing to IT / QA project management. Talk about “presto-change”!
Thanks for the response, Keith!
The initial call for volunteers, and the 27K respondents, were internet-based. It’s not a big surprise that many of them didn’t meet criteria. (Though from the flowchart I would bet that not all of the detailed criteria were spelled out in advance.)
The study was approved for a cohort of up to 90 participants. And the approval process was probably the most rigorous in recent years. It took 10 months and involved boards and committees and academic trustees weighing the details of the proposed study against international criteria for ethical research, local laws, and their own moral sense. If the researchers had proposed a study population of 1,000 I seriously doubt their proposal would have been approved.
Yup! I’m sure the safety board was a little shaky about that protocol, too. Live, un-attenuated deadly virus!? Yikes!
Remember that when the researchers made their application, there was no vaccine. By the time it was approved and the study started, both vaccine and, more important to this study, monoclonal antibody treatments existed. So the risk of progression to severe disease, already low because of the age & condition of the volunteers, was rendered even lower. The protocols had strict criteria that would have triggered mAb treatment if any subject showed particular symptoms.
In other words, the real risk to the participants was quite low. They exchanged 2 weeks of their lives, plus follow-up, for £4,500 and had little concern about it. Long Covid, what dat? But no bad outcomes were recorded.
Another extremely helpful issue! (I know it’s a “post” but it has become a “publication” for me.)
Ron’s career change reminds me that my first full-time job involved creating interactive multimedia lessons, and pharmaceutical companies were our biggest clients. I even joined American Medical Writers Association and in 1982-83 served as the chair of their Multimedia section. (During my term I had a breakdown for unrelated reasons, but still it was an honor.) Most of the AMWA members in multimedia were using laserdiscs for various interesting applications … ah, memories!