COVID 19 update, June 5, 2020: ex-MI6 chief drops bombshell; “chaos disguised as strategy”; Trump admin selects shortlist of five vaccine candidates

(1) The former head of MI6 (the UK’s foreign intelligence service — its CIA if you like), Richard Dearlove, says flat-out COVID-19 was engineered in a Chinese lab but escaped from there. 

He continues:

Although he did not believe that the Chinese released the virus intentionally, Sir Richard told the Telegraph that the Chinese regime handled the outbreak very differently from the way a Western government might have dealt with it, and that the incident should be a wake-up call for the rest of the world on underestimating the scope of Chinese global ambitions. 
“Look at the stories… of the attempts by the leadership to lockdown any debate about the origins of the pandemic and the way that people have been arrested or silenced,” he said. “I mean, we shouldn’t really have any doubt any longer about what we’re dealing with. 
“Of course, the Chinese must have felt, well, if they’ve got to suffer a pandemic maybe we shouldn’t try too hard to stop, as it were, our competitors suffering the same disadvantages we’ve got. 
“Look, the Chinese understand us extremely well. They have made a study of us over the last decade or longer, particularly through attending our universities. We understand the Chinese very poorly. It’s an imbalanced relationship in that respect.” 
Australia has been taking the lead on pushing for an “impartial, independent and comprehensive evaluation” of the global response to COVID-19, an ambition which was agreed to by the World Health Organization in late May. China launched cyberattacks and trade restrictions against the Antipodean state in response. 
“I think it’s very courageous of the Australians to take China on,” Sir Richard said. “I mean, there’s an obvious, huge imbalance in terms of power, both economic and military and political, but they are showing the way. You have to have a critical relationship with China.” 
He urged the British authorities to do the same, calling for the government to scrap plans to place the construction of Britain’s new 5G network in the hands of Chinese telecoms firm Huawei, and to reduce reliance on Chinese-made personal protective equipment for health workers. 
“We need to go into reverse,” he said. “It’s important that we do not put any of our critical infrastructure in the hands of Chinese interests. So telecommunications, Huawei, nuclear power stations, and then things that, you know, we require and need in a crisis, like PPE.” 
“We have allowed China so much rope that we are now suffering the consequences, and it’s time to pull the rope in and to tighten the way we do business. It’s very, very important that we keep a keen eye on this and do not allow the Chinese to, as it were, benefit strategically from this situation that has been imposed on all of us.”

Wow.  

(2) Die Welt (in German) continues to pour withering criticism on the Swedish sonderweg. They call it “chaos disguised as strategy” (Chaos getarnt als Strategie). Private corporations are now stepping up with immunity testing for pay. Due to high demand, they had to limit their offerings to Sweden’s two largest cities, Stockholm (by far hardest hit) and Göteborg, but other companies are looking to fill the void. 

Sweden’s chief epidemiologist, Prof. Anders Tegnell, gave a remarkably self-critical interview on Swedish radio: “Too many have died too soon”. He regrets not having been more proactive to protect the most vulnerable. My translation (2nd hand via German): “I believe there is definite room for improvement in what we ‘ve been doing in Sweden, of course., And it would have been good if we’d known more precisely what to close to prevent infection spread.” Also, he said, if we’d encountered the same epidemic but with the knowledge we have today, then the correct course in his opinion lay intermediate between the road Sweden took and what the rest of the world did. “Unambiguously, we could have done better in Sweden, I believe.”

(3) Operation Warp Speed, an initiative of the White House, selected a shortlist of five vaccine candidates for mass manufacturing in the US

The five vaccines include Moderna’s mRNA1273, currently in phase 2 trials; AstraZeneca and Oxford University’s AZD1222, now in clinical trials at multiple UK sites; a candidate from Johnson & Johnson; a Merck vaccine based on that company’s successful Ebola vaccine; and Pfizer and BioNTech‘s BNT162.

The accelerated programs are funded through $10 billion from Congress and $3 billion directed for National Institutes of Health (NIH) research.

Earlier this week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said he was confident more than one COVID-19 vaccine would prove effective in a reasonable period of time.

Francis Collins, MD, NIH director, said some vaccine candidates will be ready for large-scale testing as soon as the beginning of July. The phase 3 trials would involve as many as 30,000 volunteers for each candidate vaccine, with half the volunteers receiving a placebo, Collins told National Public Radio.

If successful, this will be the most rapid vaccine development program in history.

 

ADDENDUM: GenomeWeb reports that another Surgiscape-sourced paper, in the New England Journal of Medicine, has now been retracted. 

The Lancet and the New England Journal of Medicine have retracted two COVID-19 papers because of questions regarding the data used in the studies. The papers were both previously the subject of expressions of concern.

The now-retracted Lancet paper had reported that the antimalarial drugs hydroxychloroquine and chloroquine may increase the risk of death among COVID-19 patients, while the now-retracted NEJM paper noted that though cardiovascular disease increases someone’s risk of dying from COVID-19, ACE inhibitors did not increase that risk.

Both studies relied on a database run by Surgisphere, which said it had detailed data on about 100,000 COVID-19 patients from 1,200 hospitals around the world, but as the New York Times noted earlier this week, clinicians and medical researchers have raised concerns about the data it houses.

The authors of the Lancet study who were not associated with Surgisphere noted in the expression of concern that they would be seeking an independent audit of the data. However, in the retraction notice, they wrote that Surgisphere would not transfer the full dataset to its independent reviewers, citing client agreements and confidentiality. Because of this, the Lancet notes in a statement that three of the four authors — the fourth author being Surgisphere chief executive Sapan Desai — said they “can no longer vouch for the veracity of the primary data sources.” 

The NEJM retraction notice similarly says that the authors, this time including Desai, could not “validate the primary data sources” and requested a retraction.

COVID19 update, June 4, 2020: is the virus a picky eater; co-authors of influential Lancet hydroxychloroquine study retract paper

(1) Somebody quipped to me the other week: “the virus is a picky eater”. Now, Prof. Karl Friston of UC London, a well-known neuroscientist and computational modeler who is a member of “the independent SAGE committee” is interviewed here on UnHerd.

Now, from the unlikely source of a prominent member of the “Independent SAGE committee”, the group set up by Sir David King to challenge government scientific advice and accused by some of being populated with Left-wing activists, comes a claim that the true portion of people who are not even susceptible to Covid-19 may be as high as 80%.

 

A written essay is here. His thesis: 

Theories abound as to which factors best explain the huge disparities between countries in the portion of the population that seems resistant or immune — everything from levels of vitamin D to ethnic-genetic and social and geographical differences may come into play — but Professor Friston makes clear that it does not primarily seem to be a function of government coronavirus policy. “Solving that — understanding that source of variation in terms of this non-susceptibility — is going to be the key to understanding the enormous variation between countries,” he said.

Controversial? We link, you decide.

(2) The Washington Examiner reports that the influential The Lancet paper, which claimed hydroxychloroquine was more harmful than helpful in the treatment of COVID19 based on dodgy Surgisphere data, has now been retracted by 3 of the 4 authors (the 4th is the CEO of Surgisphere). Here is the original retraction notice:

https://www.thelancet.com/lancet/article/s0140673620313246

After publication of our Lancet Article,1 several concerns
were raised with respect to the veracity of the data
and analyses conducted by Surgisphere Corporation
and its founder and our co-author, Sapan Desai, in
our publication. We launched an independent third-
party peer review of Surgisphere with the consent of
Sapan Desai to evaluate the origination of the database
elements, to confirm the completeness of the database,
and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that
Surgisphere would not transfer the full dataset, client
contracts, and the full ISO audit report to their servers
for analysis as such transfer would violate client
agreements and confidentiality requirements. As such,
our reviewers were not able to conduct an independent
and private peer review and therefore notified us of their
withdrawal from the peer-review process.

We always aspire to perform our research in accordance
with the highest ethical and professional guidelines. We
can never forget the responsibility we have as researchers
to scrupulously ensure that we rely on data sources that
adhere to our high standards. Based on this development,
we can no longer vouch for the veracity of the primary
data sources. Due to this unfortunate development, the
authors request that the paper be retracted.

We all entered this collaboration to contribute
in good faith and at a time of great need during
the COVID-19 pandemic. We deeply apologise to
you, the editors, and the journal readership for any
embarrassment or inconvenience that this may have
caused.

The accompanying statement by the Lancet editorial board:

Statement from The Lancet
Today, three of the authors of the paper, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis”, have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they “can no longer vouch for the veracity of the primary data sources.” The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics (COPE) and International Committee of Medical Journal Editors (ICMJE), institutional reviews of Surgisphere’s research collaborations are urgently needed.

(3) Elsewhere in the Lancet is an article with a “meta-analysis” of other studies (in plain English: a study in which the raw data of several original lstudies are combined into a larger dataset and the statistical analysis repeated in order to achieve greater productive power than the individual studies)  on the effectiveness of distancing, face masks, and eye protection, in both  healthcare and non-healthcare (community) settings.

https://doi.org/10.1016/S0140-6736(20)31142-9

From the summary (paragraphing and emphasis mine):

Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients).

Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] –10·2%, 95% CI –11·5 to –7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; p_interaction=0·041; moderate certainty).

Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD –14·3%, –15·9 to –10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; p =0·090; posterior probability >95%, low certainty).

Eye protection also was associated interaction with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD –10·6%, 95% CI –12·5 to –7·7; low certainty).

Unadjusted studies and subgroup and sensitivity analyses showed similar findings.

 

ADDENDUM: “WHO frustrated by China’s info delays as coronavirus started to spread, report finds”. Is this damage control/reputation management on the part of the WHO, or the genuine expression of frustration by the technical levels of the organization? More about this tomorrow, G-d willing.

COVID19 update June 3, 2020: serological study in Israel; Surgisphere data scandal [UPDATED]

(1)  Israel is planning to test a sample of 70,000 people for antibodies. Earlier, preliminary result from a smallish sample of 1,709 Israelis found that 2.5±0.5% had antibodies for the virus. With official infection numbers (positive tests in RT-PCR) reaching only 0.2% of the population, this implies a Dunkelziffer  (stealth infection rate) of 10-15 times the official one — not dissimilar from what Prof. Hendrik Streeck found in Germany or the team of Ioannides, Bendavid et al. found in Santa Clara County, CA. [For non-American readers: Santa Clara County is almost synonymous with Silicon Valley.] 

With just 291 dead out of 17,377 confirmed cases — a raw case fatality rate (CFR) of 1.67%, this implies that the infection fatality rate is just 0.11–0.17%. This is considerably lower than even the drastically downward-revised CDC figures,  (IFR of about 0.26%), but Israel has a much younger population pyramid than the USA, and is sunny enough that vitamin D deficiency should not be as prevalent as in  northern US states.

Meanwhile, Israel is seeing a flare-up of cases in schools that has some people speaking of a second wave, although it might actually be more like a ripple, or a round of the dance in Tomas Pueyo’s “Hammer and Dance” strategy. Rungholt blogs in German about her experience as a kindergarten teacher in a kibbutz in the far North of the country.

(2) h/t: Cathe Smith: several papers, including the one that led to suspension of the hydroxychloroquine trials, now under a cloud owing to suspect medical database

On its face, it was a major finding: Antimalarial drugs touted by the White House as possible COVID-19 treatments looked to be not just ineffective, but downright deadly. A study published on 22 May in The Lancet used hospital records procured by a little-known data analytics company called Surgisphere to conclude that coronavirus patients taking chloroquine or hydroxychloroquine were more likely to show an irregular heart rhythm—a known side effect thought to be rare—and were more likely to die in the hospital.

Within days, some large randomized trials of the drugs—the type that might prove or disprove the retrospective study’s analysis—screeched to a halt. Solidarity, the World Health Organization’s (WHO’s) megatrial of potential COVID-19 treatments, paused recruitment into its hydroxychloroquine arm, for example. (Update: At a briefing on 3 June WHO announced it would resume that arm of the study.)

But just as quickly, the Lancet results have begun to unravel—and Surgisphere, which provided patient data for two other high-profile COVID-19 papers, has come under withering online scrutiny from researchers and amateur sleuths. They have pointed out many red flags in the Lancet paper, including the astonishing number of patients involved and details about their demographics and prescribed dosing that seem implausible. “It began to stretch and stretch and stretch credulity,” says Nicholas White, a malaria researcher at Mahidol University in Bangkok.

Today, The Lancet issued an Expression of Concern (EOC) saying “important scientific questions have been raised about data” in the paper and noting that “an independent audit of the provenance and validity of the data has been commissioned by the authors not affiliated with Surgisphere and is ongoing, with results expected very shortly.”

Hours earlier, The New England Journal of Medicine (NEJM) issued its own EOC about a second study using Surgisphere data, published on 1 May. The paper reported that taking certain blood pressure drugs including angiotensin-converting enzyme (ACE) inhibitors didn’t appear to increase the risk of death among COVID-19 patients, as some researchers had suggested. (Several studies analyzing other groups of COVID-19 patients support the NEJM results.) “Recently, substantive concerns have been raised about the quality of the information in that database,” an NEJM statement noted. “We have asked the authors to provide evidence that the data are reliable.”

A third COVID-19 study using Surgisphere data has also drawn fire. In a preprint first posted in early April, Surgisphere founder and CEO Sapan Desai and co-authors conclude that ivermectin, an antiparasitic drug, dramatically reduced mortality in COVID-19 patients. In Latin America, where ivermectin is widely available, that study has led government officials to authorize the drug—although with precautions—creating a surge in demand in several countries.

Chicago-based Surgisphere has not publicly released the data underlying the studies, but today Desai told Science through a spokesperson that he was “arranging a nondisclosure agreement that will provide the authors of the NEJM paper with the data access requested by NEJM.”

UPDATE (h/t LIssa Hailey): much more at The Guardian (archive copy here) “Governments and WHO changed Covid-19 policy based on suspect data from tiny US company”

A search of publicly available material suggests several of Surgisphere’s employees have little or no data or scientific background. An employee listed as a science editor appears to be a science fiction author and fantasy artist. Another employee listed as a marketing executive is an adult model and events hostess.

[…] Until Monday, the “get in touch” link on Surgisphere’s homepage redirected to a WordPress template for a cryptocurrency website, raising questions about how hospitals could easily contact the company to join its database.

[…] At a press conference on Wednesday, the WHO announced it would now resume its global trial of hydroxychloroquine, after its data safety monitoring committee found there was no increased risk of death for Covid patients taking it.

The article refers to an earlier expose at MedicineUncensored.

COVID19 update, June 2, 2020: Remdesivir Phase 3 trial results

A short post today, as the day job is keeping me busy. 

 

(1) Today the results of the Phase 3 remdesivir trial were released. (I previously discussed its mechanism of action here: in brief, it’s a nucleoside analog that interferes with viral RNA copying by acting as an “imposter letter” in the RNA genetic code and causing further copying to break off.)

Again, as with prior trials, we see that it’s not a “magic bullet” drug, but clearly has a therapeutic advantage  in patients with moderate disease (signs of pneumonia, but don’t yet need oxygen). The trial used almost 600 patients, divided into three roughly equal groups: (a) standard of care (SOC) + 5-day remdesivir; (b) SOC + 10-day remdesivir; (c) SOC only (control group). In the table below, percentages are given in parentheses:UntitledImage

The “ordinal scale” is an ad hoc 7-point scale ranging from hospital discharge on one end to death on the other end. In the 5-day regimen (which I read between the lines uses twice the dose for half the time), about 10% more patients see an improvement, and 8% fewer patients see a worsening from baseline than with SOC. No patients on the 5-day regime died (compared to four with SOC), but we are in “statistics of small numbers” territory.

As for drug side effects (“AE”), there are about 6% more than with standard care, but actually fewer serious side effects.

Additional Phase 3 trials in severe and moderate disease are in progress in various countries. The drug is currently approved in Japan and under FDA emergency authorization in the US.

 

(2) A few videos:

A 60 Minutes Australia documentary on the Chinese cover-up (see also my earlier post about Fang Fang’s “Wuhan Diary”)

In this video, Dr. Seheult talks about masks and about a database for vaccine clinical trials.

 

 

ADDENDUM: Israeli-developed “disinfection tunnel” sprays harmless disinfectant aerosol generated electrolytically from water and salt

COVID19 update, June 1, 2020: Sweden’s “road alone” and elderly care; avoiding lockdowns in a new flare-up; not even Stanford immune from cuts and layoffs

 

(1) Sweden’s Sonderweg (“special road”, idiomatically, “going its own way”) is the subject of heated debate pro and con.

At first sight, per capita mortality is an order of magnitude higher than in adjacent countries with similar ethnic profile, climate, and sociology. (Sweden does, however, have a higher percentage of 1st-generation immigrants than Norway, Denmark, and Finland — see below.)

At second sight, however, it turned out that Swedish morbidity and especially mortality is disproportionately concentrated in two populations: elderly in care homes (over 70%) and 1st-generation immigrants. Mortality among native Swedes from young to independent elderly, is actually not that elevated compared to the neighbors. 

On the gripping hand, while the Swedes may have avoided the economic ruination of a full lockdown and may be closer to herd immunity now should a second wave arrive, there are costs to this epidemic for everyone (the travel and airline industries, for instance, are on life support everywhere, lockdown or no lockdown). Some aspects of the world economy will be changed forever — and some already existing ‘creative destruction’ trends will be accelerated worldwide. Sweden will see a recession, just not as deep, and possibly with a quicker recovery. 

But let’s come back to those care homes. Die Welt has an exposé on what is going on there: “The true problem of the Swedish sonderweg“. If it were in English, I’d say “read and weep”. But as it’s in German, let me summarize a few points (reader beware):

  • As explained earlier, the Swedish elderly care model is based on encouraging people to live independently for as long as possible, with paid ‘home helpers’ if needed. Assisted living facilities seem to be primarily a private-sector option, while true homes for the elderly are seen as the last resort. Median survival time in them is less than a year
  • Caregivers in these homes were alleged not issued PPEs, and testing was only carried out people who showed symptoms, despite adequate testing capacity being available.
  • The Swedish newspaper Aftonblådet quoted gerontologist Prof. Yngve Gustafsson of Umea University as saying that 70-80% of care home residents admitted to geriatric hospitals with COVID-19 are sent back to the care home. Residents checked into the hospital with COVID19 were often sent back to the home, where of course the infection then spread.
  • He adds that in many cases they don’t die from COVID19 but from secondary infection with bacterial pneumonia, and could be saved with intravenous antibiotics. However, the prescribed care protocol for such patients is purely palliative — Morphin, Midazolam and Haldol – which according to him is a nearly 100% certain death sentence
  • A man named Thomas Andersson, who discovered that his father Jan, aged 81 had been put on this protocol (following diagnosis over the phone!) managed to get the decision reversed after first contacting the care home management, then going to the media. His father was put on an antibiotic IV and, once the bacterial pneumonia receded, managed to fight off the relatively mild COVID19 infection on his own. Below is Jan celebrating his recovery with children and grandchildren. Thomas still cannot believe such a thing was possible in Sweden.

Infuriating and appalling as such stories may be, they have a flip side: that if Sweden hadn’t gone “full Cuomo” on its elderly, its mortality might well have been a fraction of what they have now, and Sweden’s sonderweg might look a good deal better.

(2) Israel is, sadly, seeing a spike in new infections, almost all of them at a few schools in the Jerusalem area. Prof. Eli Waxman of the Weizmann Institute, who led the team that laid out Israel’s COVID19 planning,  discusses here how to handle a possible 2nd wave without lockdowns.

It sounds a lot like what  Norway envisages as its strategy for a second wave: individual test, track and trace as the first line of defense, where speed is of the essence; localized isolation measures as a second line of defense; expanding the ring of those if necessary; but national lockdown only as a very last resort. (It sounds like nobody in Israel, Norway, nor for that matter Belgium has any stomach for a second lockdown. This is especially true as Norway is wondering, with hindsight in numbers, if voluntary social distancing might night have been adequate. Your mileage may vary, of course — Norwegians and Italians, for example, would react very differently to strong social distancing recommendations.)

[…] In Israel, the HaMagen [“The Shield”] app, which was developed and endorsed by the Health Ministry and can tell people if they have been in the presence of anyone who has been diagnosed with coronavirus, could play a key role, he said. “The more people who download it, the better.” 
[In addition, the] Shin Bet [Israel’s domestic security service] was reported to have traced a third of Israel’s coronavirus cases, some 4,089 people, [through their cell phones.  Israel’s Supreme Court has however ruled that this cannot continue past the emergency order, unless anchored in law.]

[…] Waxman said South Korea has two advantages over Israel: It learned the importance of moving fast from its experience with Middle East Respiratory Syndrome (MERS) in 2015, when the virus killed 36 people, infected 186 and put thousands of citizens into isolation. The outbreak was ultimately traced to a single visitor from overseas. 
In addition, South Korea has leveraged some technological tools that “Israel cannot and should not be able to use” because they might infringe on privacy rights, he said.

 

(3) One “industry” which will be hit hard is higher education. Especially in the US, much of it is built upon an unsustainable base, with people paying extortionate tuition for amenities and administrative overhead that has nothing to do with education — be it the country-club level gym and dormitories, the football stadium (which only in a few places is net profitable), or the ever-expanding army of administrators. Now that these places were forced to move to distance learning, they found themselves competing with much cheaper online colleges. Instapundit has endlessly blogged (and written a book) about the “Higher Education Bubble” and the coming wave of creative destruction in that industry: COVID19 only accelerated a process waiting to happen. I had always assumed, however, that blue-chip brandnames like Harvard would be largely insulated. 

Now it turns out that not even Stanford (!) is fully immune, as revealed in a statement by the president

Many of our income streams will continue to be diminished: Housing revenue will be reduced due to fewer students living on campus; income-producing events and programs will continue to be limited; and clinical, research and philanthropic income streams will be challenged. At the same time, expenses in some areas, such as student financial aid, will increase. The market volatility affecting our endowment also can be expected to continue, given the seismic disruptions occurring in the national and global economies.

[…]

We previously asked university units to prepare FY21 budget plans based on a scenario with a 15 percent reduction in funding from endowment payout and a 10 percent reduction in support from general funds. We sincerely hope that the reductions needed will be smaller than this, but for now we need to plan to these targets as a contingency. We expect to provide final allocations of general funds and endowment payout to units by the end of June, enabling them to finalize their budgets in July.

As units plan for budget reductions, we expect there will be reductions in some of the programs each of them is able to offer. We will work to ensure that any program reductions still allow us to sustain Stanford’s core academic strengths and our long-standing commitments to student access.

Given the magnitude of the budget challenge, we also expect that program reductions will make some workforce reductions unavoidable as we enter the new fiscal year. We don’t yet know the scale of job reductions. We hope they will be limited, but they will be driven by the program needs and budget capacity of individual units. Our expectation is that some of these reductions will be temporary layoffs (furloughs) until we are able to resume services and bring employees back, and that other reductions will be permanent layoffs. At this time, we expect to be able to communicate more detailed decisions about layoffs in late July.

It would be too much to hope that the “programs” affected would primarily be silliness such as courses on “the poetics of the lowrider” (as Victor Davis Hanson has described elsewhere), rather than the STEM programs that made Stanford such a powerhouse. But never underestimate the reverse Midas touch of professional college administrators…. 

 

(4) And just because: “June came upon us much too soon…”