About that May 22, 2020 Lancet Article on the Efficacy and Safety of Hydroxychloroquine

On May 22, 2020 one of the top medical journals in the world, The Lancet, published the article, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis.” Hydroxychloroquine (Plaquenil) is prescribed tens of millions of times annually as a prophylaxis and treatment for malaria, as well as a treatment for rheumatoid arthritis, lupus, and other conditions. Several decades old and determined to be safe, including for children and pregnant women, it is considered one of the world’s essential medicines. Chloroquine (Aralen) is also an antimalarial agent. Macrolides are a class of antibiotics that includes azithromycin (Zithromax), clarithromycin (Biaxin), erythromycin, and fidoximycin (Dificid). Zithromax, or Z-Pak, is a commonly known broad spectrum antibiotic, also well known for its increased risk of fatal heart problems.

Despite a large body of anecdotal evidence that hydroxychloroquine alone or in combination with azithromycin is safe and efficacious in the treatment of COVID-19, as well as a prophylaxis (that is, a preventative), the Lancet study did not demonstrate the efficacy of either drug in any combination in treating hospitalized COVID-19 patients (they did not evaluate the efficacy of hydroxychloroquine or chloroquine as a prophylaxis). The research included a large number of patients (96,032 total) from 671 hospitals around the world (65.9% from North America).

Much has been made of these findings in the media, which has been critical of hydroxychloroquine ever since the President of the United States, who has advocated for the drug, announced that he has been taking it (as have many others, including physicians and nurses working with COVID-19 patients) prophylactically. A retrospective observational review of 368 men with COVID-19 treated at the US Veterans Affairs hospitals drew considerable press attention when it purported to show that the use of hydroxychloroquine was associated with a greater hazard of death. However, subsequent examinations of the study have found several problems with it (especially surrounding the baseline characteristics among the groups) and cannot rule out the possibility of bias. The Lancet study was careful to minimize bias in its sampling, included a much larger number of patients who were hospitalized between Dec 20, 2019 and April 14, 2020 with a positive laboratory finding for SARS-CoV-2. This was the study the media had hoping for.

Wait, what? Patients hospitalised for COVID-19 on December 20 2019? With a positive laboratory finding for SARS-CoV-2?

According to the World Health Organization, the Wuhan Municipal Health Commission in China reported a cluster of cases of pneumonia in Wuhan, Hubei Province on December 31, 2019, but the cause was mysterious and they did not believe there was human-to-human transmission (they claimed instead that the pneumonia was associated with exposure to pathogens in a wet market in Wuhan, a line WHO pushed as late as January 14, 2020). On January 7, 2020, Chinese health authorities reported that this cluster was associated with a novel coronavirus. Airway epithelial cells from infected patients were used to isolate the virus, which was named the SARS-CoV-2, and the virus sequence was publicly released. This gave authorities around the world the information they needed to develop tests for the virus.

The Lancet study identifies at least one patient hospitalized on December 20, 2019. Positive cases were not diagnosed on the basis of observation of the (ever-growing) cluster of symptoms associated with COVID-19 but were selected based on positive laboratory finding for SARS-CoV-2. From the study: “A positive laboratory finding for SARS-CoV-2 was defined as a positive result on high-throughput sequencing or reverse transcription-quantitative PCR assay of nasal or pharyngeal swab specimens, and this finding was used for classifying a patient as positive for COVID-19.” Moreover, “COVID-19 was diagnosed, at each site, on the basis of WHO guidance.”

How do doctors have tests for a virus in mid-December that is specifically unknown to scientists until the first week of January?

The first first confirmed case of SARS-CoV-2 infection in the United States was reported on January 20, 2020. A man who had returned to Washington State on January 15 after traveling to visit family in Wuhan, China, sought medical attention after feeling ill. His case is reported in great detail in an article in The New England Journal of Medicine. The test described in NEJM article is the test described in the Lancet article. The NEJM article states: “Clinical specimens were tested with an rRT-PCR assay that was developed from the publicly released virus sequence.”

It is possible that preserved samples were used to retrospectively determine cases dating back to December 20, several days before the initial cluster of cases were reported by Chinese authorities. One can understand why Z-Pak would be used to treat an unidentified pathogenic in pneumonia cases (as their eitlogy may be bacteriological), but chloroquine and hydroxychloroquine? Perhaps some physicians used chloroquine and hydroxychloroquine upon suspicion that malaria was the cause of the symptoms they were seeing, but this is doubtful given the constellation of symptoms described. After all, their attention was drawn to the unusual aspects of the disease, which had caused them to strongly suspect a SARS virus.

There are questions to be asked of the time line. The question that first comes to mind: How long were the Chinese Communist Party and Director-General of the World Health Organization Tedros Adhanom withholding knowledge about this virus from the world?

Published by

Andrew Austin

Andrew Austin is on the faculty of Democracy and Justice Studies and Sociology at the University of Wisconsin—Green Bay. He has published numerous articles, essays, and reviews in books, encyclopedia, journals, and newspapers.

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