COVID19 update, June 25, 2021: the delta and “delta+” variants; ivermectin

(a) Israel has reintroduced indoor face masks effective noon today, following two outbreaks in schools in the cities of Binyamina and Modi`in. Both outbreaks appear to be the delta (“Indian”) variant (lineage B.1.617.2), imported by returnees from vacations abroad, and particularly by unvaccinated returned children. (Israel has opened vaccinations for ages 12-15 only very recently, but the public health authorities were not promoting it, just keeping it as an option.)

Public health authorities seem to be in a “let’s nip this one in the bud” mode. From July 1, vaccinated tourists were supposed to be able to enter immediately without any quarantine (not even the 1 day typically required for an antibody test — unlike many countries, Israel considers vaccinees and recovered patients largely equivalent). This has now been postponed by a month.

Experts doubt that this delta variant will lead to anything resembling the last major outbreak. There was concern that delta could be an “escape mutation”, i.e., one that can bypass the vaccine protection. However, data are available from the UK, where the delta variant has outcompeted the alpha (“British”) variant and is now responsible for essentially all new cases. The UK uses both Pfizer and Oxford-AstraZeneca vaccines. According to a June 14 report from Public Health UK [details here], two shots of Pfizer are 96% [uncertainty interval: 86–99%] protective against hospitalization, compared to 92% [UI: 75-97%] for Oxford-AstraZeneca. Single shots of either vaccine (especially Oxford/AstraZeneca) protect noticeably less from the delta than from the alpha variant — this is an issue in the UK which followed a “maximum first jabs first, only then second jabs” strategy, unlike Israel where almost everybody got their second shots within 3 weeks.

I would say caution is required, and it is probably best to act while there is time to do so without economically crippling measures — but like Prof. Eran Segal of the Weizmann Institute, I very much doubt we will go back to the situation during the last wave.

Israel: Surge in Delta variant cases

Is Israel in danger of a return to many (>500) critically ill patients? I think chances are low

Yet, some steps should be taken to prevent the surge

And remember that all Covid-19 analyses are true for their time and subject to change

>>> pic.twitter.com/GXQ5MZtnDN

— Eran Segal (@segal_eran) June 25, 2021

(b) This is my face. It is shocked. Countries that relied on Sinovac, such as Chile or some of our Arab neighbors, now find that Sinovac works as “well” as one would expect from a “gift” by Chairman Xi the turtle-“lover”. [NYT link; archive copy]

(c) now a “delta+” variant is getting mentioned in the press. What is this even? “Delta+” refers to the delta variant with one additional mutation in the spike protein: K417N, or in plain English: at position 417, it has Asparagine (N) instead of Lysine (K).

Amino acids are referred to in research by two compact notations: three-letter codes which are easy to remember, and single-letter codes which take a bit getting used to. Mutations in which a single amino acid in a protein is replaced by another are denoted XnY, where n is the position in the protein sequence, X the one-letter code of the wild-type amino acid, and Y the one-letter code for the substitute in the mutant.

Prof Ravi Gupta, Professor of Clinical Microbiology, University of Cambridge, said:

“As yet there is no clear evidence that the AY.1 is more transmissible or immune evasive than the Delta Variant.  The K417N mutation has previously occurred on a background of Alpha variant, without significant increased expansion in cases, and now Delta; it likely has little effect on infectiousness of the virus and could have a small effect on antibody binding responses post vaccination.”

(d) Dr. John Campbell [congratulations on hitting the 1M subscriber milestone on Youtube!] draws attention to a recently published meta-analysis of clinical trials with the cheap antiparasitic ivermectin.

The drug had earlier been shown to inhibit the replication of the virus in vitro — see https://doi.org/10.1016/j.antiviral.2020.104787 — but that’s still a big step away from whether it will work in actual human patients. This newest meta-analysis, however, does seem to represent a positive answer:

Bryant, A.; Lawrie, T. A.; Dowswell, T.; Fordham, E. J.; Mitchell, S.; Hill, S. R.; Tham, T. C. Ivermectin for Prevention and Treatment of COVID-19 Infection. Am. J. Ther. 2021, ASAP, 1–25. http://doi.org/10.1097/MJT.0000000000001402

Let me just quote the abstract:

Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19–0.73; n = 2438; I² = 49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the same DerSimonian–Laird method that underpinned the unadjusted analysis. This was also robust against a trial sequential analysis using the Biggerstaff–Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%–91%). Secondary outcomes provided less certain evidence. Low-certainty evidence suggested that there may be no benefit with ivermectin for “need for mechanical ventilation,” whereas effect estimates for “improvement” and “deterioration” clearly favored ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty.

Conclusions:

Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.

But you could get censored by Facebook or YouTube for saying this last year. [The “big pharma conspiracy” theory is not entirely convincing: the corticosteroid dexamethasone, likewise dirt cheap, and quite beneficial in tamping down on ARDS in severe patients, has meanwhile become an accepted part of hospital treatment.]