The delta variant and its further evolution are causing quite some uncertainty, not at least amongst the loyal “corona army” of medics and volunteers who are committed to the fight against the virus. This “wicked variant” it is not only highly infectious and more pathogenic; it also causes more breakthrough infections than previous VOC and it seems to get even more dangerous by additional mutations.
This constellation undermines the public confidence in vaccination, exactly at the time that we need to convince the vaccine-sceptics and the youngsters to get vaccinated, in order to reach sufficient herd immunity for the coming Fall and Winter season.
What is the latest published clinical, epidemiological and virological evidence and how concerned should we be about it? In this episode, I will focus on the clinico-epidemiological aspect
Ep 166-1 : Interesting (and rather reassuring) case report by Nathan in JID: SARS-CoV-2 variant Delta infects 6 siblings (1 with co-morbidities hospitalized) but spares Pfizer-vaccinated parents
Ep 166-2: Musser in medRxiv 1 Aug: Delta causes increased breakthrough in Houston
From 4920 sequenced viruses between March 15 and July 24: 23 % delta and 77 % other variants
- Only 8.4 % breakthrough in fully vaccinated subjects
- But Delta breakthrough = overrepresented at 17.4 % > other variants = 5.8 %
- Vaccinated subjects generally lower viral load, but this was NOT the case for Delta: similarly high viral load in unvaccinated and fully vaccinated subjects
Fourteen patients with Delta Plus (Delta plus the K417N) were identified, all in July.
Ep 166-3 : Riemersma in medRxiv 24 Aug show that the virus in breakthrough infections is really as infectious as in unvaccinated subjects, strongly suggesting transmission capability.
Ep 166-4 : Kissler in medRxiv 25 Aug on viral dynamics in almost 200,000 NP swabs, taken from the National Basketball Association between Nov 28 and Aug 11:
- Mean viral trajectories were similar in non-variant, alpha and delta infections
- Vaccine breakthrough (BTI) and unvaccinated had similar peak (Ct20) and prol:iferation time (3.2-3.5 days), but the clearance in BTI was faster than in non-vaccinated (5.5 vs 7.5 days).
Ep 166-5 : Hammerschmidt in CMI: heterologous ChAdOX1 (AZ) prime, followed by Pfizer boost results in higher delta-neutralizing Ab than AZ homologous prime-boost, but equal to Pfizer homologous
→ People fully vaccinated with AZ could take advantage of a Pfizer boost?
Ep 166-6 : Puranik in medRxiv 21 Aug 2021. Epidemic shift from alpha early 2021 to delta July
- Effectiveness of mRNA vaccines decreased:
- More breakthrough infections: increases from Feb to July, but remains low: 0.12 per 1000 person-Days for Pfizer versus O.054 per 1000 for Moderna. Hence Moderna twofold lower risk than Pfizer.
Ep 166-7 : Interesting study from Singapore in CID, comparing pathogenicity (pneumonia), showing (marginal) increase for delta and clear decrease for alpha and beta. Also very clear protective effect of vaccination.
Ep 166-8 : Catherine Brown in MMWR 6 Aug:
July 2021, in a Barnstable County, Massachusetts:
- 3 July: zero COVID per 100,000
- 17 July: 177 COVID cases per 100,000 following multiple large public events, many indoor with high density
Of the 469 COVID-19 cases among Massachusetts residents who had traveled to the town
- 74% occurred in fully vaccinated persons.
- Delta in 90% and 1 Delta AY.3.
- Ct (viral load) similar among specimens from fully vaccinated patients and non-vaccinated
For more background: see 166-9
Implication: Consider expanded prevention strategies, including universal masking in indoor public settings, particularly for large public gatherings that include travelers from many areas with differing levels of SARS-CoV-2 transmission.
Ep 166-9 : Nice, well explained paper in the New Yorker by Dr. Khullar on the various aspects of the present state of the epidemic and the uncertainties we are confronted with. Worth reading entirely to grasp all the nuances. The -at first-view- very disturbing case of Barnstable County (Ep 166-8) is also put into perspective.
Important very recent new data
- Ep 166-10: One study, of thousands of nursing-home residents across the country, found that, in recent months, the vaccines’ effectiveness against infection had declined from about 75 % to 53 % it’s not entirely clear what to make of the findings, however, because we don’t know when the residents were vaccinated or whether they went on to have symptoms.
- Ep 166-11: A second study, focussed on the general population of New York State during the period that Delta came to dominate, found that the vaccine efficacy against infection decreased from 92 to 80 % —and that there was no change in how reliably they prevented hospitalization well above 90 %.
- Ep 166-12: The third study, which analyzed data from eighteen states, supported the latter finding: six months after being vaccinated, people were just as protected against a covid hospitalization as they were just after they got their shots.
Over all, the evidence that vaccines prevent severe covid-19—even with Delta, even half a year after immunization—remains both clear and encouraging.
By contrast, the data that breakthrough infections present a major concern for the average American is much murkier.
When it comes to breakthrough infections…. The data are too inconclusive. But we may still choose, rationally, to make a wager. For vaccinated people, the coronavirus threat is massively, undeniably smaller than it was last year; at the same time, we are taking more risks—visiting family, attending weddings, going to church, returning to the office. We have to make decisions about what’s worth it, what isn’t, what we should do now, and what can wait. Like many Americans, I have started to scale back. I’ve cancelled trips, avoided gatherings, stopped dining indoors. In my work as a physician, I’m again wearing an N95 respirator with every patient, not just those who’ve tested positive for the virus. I’ve concluded that the risk of Delta causing a significant breakthrough illness for me—a reasonably healthy man in his thirties—is low, but also that it’s a better bet to assume that the risk is real.
As a society, we are also making bets. We are now planning third shots for healthy Americans, even as billions of people around the world have yet to receive a single dose; in all likelihood, there will be college students in the U.S. who get boosters before nursing-home residents in Africa receive their first shots. Meanwhile, we don’t know, with any certainty, the true risks of waning immunity, of breakthrough infections, of long covid, or of Delta-inflicted breakthrough disease. Still, we are deciding that the costs of waiting to find out may exceed the costs of acting today. There are differences—morally, practically, emotionally—between being forced to feel afraid and choosing to be cautious.
Ep 166-13 : Nice didactic series from CDC concerning communication strategy on Delta and vaccination (dating from end of July, but still valid in view of all evidence above weighed).
Summary slide 22
▪ Delta is different from previous strains
– Highly contagious
– Likely more severe
– Breakthrough infections may be as transmissible as unvaccinated cases
▪ Vaccines prevent >90% of severe disease, but may be less effective at preventing
infection or transmission
- More breakthrough and more community spread despite vaccination
▪ NPIs are essential to prevent continued spread with current vaccine coverage
I will stop here with the remark that in all these studies, little attention has gone to delta sublineages (such as D or AY.3), which might be very relevant in the context of escape and breakthrough. That is, however, a complicated field that is just emerging over the last few weeks.
After some other duties in the coming days, I will dedicate Episode 167 to the viral evolution aspects.
Best wishes and nice weekend
15 Oct 2021 Episode 182 : B cell memory and maturation during and after COVID and after vaccination
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6 Oct 2021 Episode 180 : Efficacy of booster, discussion on side effects, overviews on efficacy of vaccines and follow-up on novel therapeutics
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4 Oct 2021 Episode 179 More on origin, standardization of neut assays, need and effects of booster, a novel Chinese S protein vaccine and a novel immunotherapy.
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28 Sept 2021 Episode 177 : Role of T cell immunity in convalescence and after vaccination
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