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hydroxychloroquine was more harmful than helpful in the treatment of COVID19 based on dodgy Surgisphere data, has now been retracted by 3 of the 4 authors (the 4th is the CEO of Surgisphere).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:

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

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.

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.