‘The World Should Have Listened To WHO’ Says Director General Tedros; Arthritis Drug Shows Promising Results Against COVID-19 In Early Trials
Dr Tedros speaks at the 27 April WHO COVID-19 press briefing

When the World Health Organization sounded the alarm by declaring a ‘public health emergency of international concern‘ on 30 January, “the world should have listened,” said WHO Director General Dr Tedros Adhanom Ghebreyesus, in his strongest response to date, to repeated allegations by the United States that WHO failed to act quickly enough in the early days of the coronavirus pandemic.

The world should have listened to WHO carefully then, because the highest level of global emergency was triggered. This was on January 30 when we only had 82 cases and no deaths in the rest of the world,” said Dr Tedros, repeating even more adamantly messages he delivered on several occasions last week, “We advised the whole world to implement a comprehensive public health approach; find, test, and do contact tracing.

“You can take for yourselves countries who followed [our advice] are in a better position than others. This is fact,” he added.

Although the Director-General refrained from pointing fingers at specific nations, his response was clearly aimed at  US President Donald Trump, who bitterly attacked the agency for allegedly being China-centric and failing to provide sufficiently early warnings, and then suspended nearly US$ 500 million in funding – which represents some 15-20 percent of the WHO’s 2020-2021 budget. The US has now become the new epicentre of the COVID-19 pandemic – after Trump initially downplayed the risks posed by the virus and even praised China’s management.

“We don’t have any mandate to force countries to implement what we advise them,” Dr Tedros said. “WHO gives the best advice we can based on science and evidence, and it’s up to the countries to reject or accept.

“But what we have seen so far is that some countries accept [our advice] and some may not. At the end of the day, each country takes its own responsibility.”

Some 75% Of All COVID-19 Deaths Reported in Just Six Countries – Led by United States
United States tops the list of six countries with the most COVID-19 fatalities. (University of Oxford, CEBM). Orange bar indicates initial dates of state lockdowns.

In fact, some 75% of all COVID-19 deaths were reported in only 6 countries – with the United States at the top of the charts – a new analysis from researchers at the University of Oxford found. 

As of 24 April, there had been some 54,941 deaths in The United States, which suffered the biggest toll,  followed by Italy, Spain, France, the United Kingdom, and Belgium. 

These six countries together accounted for 155,457 of the 206,008 global deaths reported in the period – although they comprise only 7.5% of the global population. The sobering numbers come even as countries are slowly easing lockdown measures as new infections decrease, hoping that they have weathered the peak of the epidemic. 

New Drug Trial Results Sparks Hopes for Tocilizumab Therapy; Outcomes for Hydroxycholorquine and Remdesivir Less Positive 
How Tocilizumab may calm the “cytokine storm” provoked by immune overreaction to COVID-19

An antibody therapy used to treat inflammatory conditions associated with rheumatoid arthritis – tocilizumab – showed promising results in small, preliminary trials on COVID-19 patients in France, researchers at the Assistance publique – Hôpitaux de Paris, reported on Monday.

Given the pandemic context, “the investigators and sponsor felt ethically obligated to disclose this information,” said the investigators in a press release from the Assistance publiqueHôpitaux de Paris.

“These results should be confirmed independently by additional trials,” said a statement from the hospital press release, which was initial posted and then blocked, after having been widely reported in French media. 

The drug, produced by Roche Pharmaceuticals, is rapidly gaining attention as a potential COVID-19 therapeutic, with another Phase III clinical trial, approved by the US Food and Drug Administration, underway in the United States.

In the French trial, a 14 day course of tocilizumab was found to significantly reduce the proportion of moderate or severe COVID-19 patients who required more intensive ventilator support, or died.  

The drug works by preventing IL-6 cytokines from binding to immune cell receptors. In many severe COVID-19 cases, an overreaction of the immune system to the SARS-CoV-2 virus unleashes a wave of cytokines and immune cells, causing massive damage to the lungs that can lead to acute respiratory failure. Some scientists have posited that blocking the so-called “cytokine storm” could prevent massive lung damage. 

The trial observed 129 patients with moderate or severe COVID-19 in a multicenter randomized control trial conducted across several French hospitals. The specifics of the study will be submitted to a peer review journal pending longer follow-up in the patients.

The new US FDA-approved study on tocilizumab will enroll 330 patients in a randomized controlled trial run by Roche, the company that produces the drug, and the US government entity, Biomedical Advanced Research and Development Authority (BARDA), a branch of the US Health and Human Services Department.

Meanwhile, new results on hydroxychloroquine and remdesivir, two of the therapeutics tapped for the World Health Organization’s Global Solidarity Trial, have not so far made strong showings, in the preliminary results of human trials which have recently been reported – although these studies also have have significant limitations. 

Preliminary results of a small remdesivir study in China, accidentally posted by the World Health Organization last week, showed no significant differences in mortality after 28 days of treatment, among patients who received the drug and those who did not. In a screenshot captured by STAT News, the trial results also reported that 11.6% of the patients who had received remdesivir also stopped the drug early due to adverse effects. The trial results were quickly removed from the Clinical Trials Registry site, with WHO saying that the results were not yet conclusive. 

Screenshot of WHO Clinical Trial Registry capturing remdesivir trial results, captured by STAT News

In a statement released on Thursday, Merdad Parsey, chief medical officer of Gilead said the trial had been terminated, but expressed hopes that other studies might yield a more positive picture: “The study was terminated early due to low enrollment and, as a result, it was underpowered to enable statistically meaningful conclusion,”  Parsey said.  He claimed that “trends in the data” could indicate that remdesivir may have clinical benefit when given to patients in earlier phases of the disease.

In early February, remdesivir showed promising results against the COVID-19 virus, SARS-CoV-2, in a Chinese cell culture study. However, these results have not been replicated in human studies.

As for hydroxychloroquine, a number of recent studies and warnings have emerged to the effect that the high doses required to combat the virus may also prove fatal to some patients.  Those include a study in Brazil, which was terminated early due to adverse effects.

Last Thursday, a retrospective analysis of outcomes among some 368 US patients treated with the drug, or with the drug in combination with azithromycin,  found “no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19.”  The study of patients treated in US Veterans Health Administration medical centres, also found an association of increased overall mortality in patients treated with hydroxychloroquine alone.

At the same time, researchers have not given up on the drug. A 400-person Phase III Clinical trial was announced last week by Swiss authorities for the hydroxychloroquine as well as the HIV drug lopinavir/ritonavir. The trial is to be run by the Geneva University Hospitals, Basel University Hospital and the Swiss Tropical and Public Health Institute. There are currently over 60 clinical trials of various drug combinations underway in Switzerland.

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Switzerland began today its first phase of a three-stage re-opening. Hospitals resumed all medical procedures, including elective surgeries. Caps on funerals, which were restricted only to close family members, were lifted. Businesses offering low levels of direct contact, such as hairdressing salons, massage practices, tattoo and cosmetic studios, florists, garden centres, and DIY stores, were reopened. 

Similarly New Zealand’s Prime Minister Jacinda Arden, who has been praised for her handling of the pandemic, announced Monday that the country was deescalating from a level four to level three emergency as new infections dropped into the single digits.

Yesterday, the Italian Prime Minister Giuseppe Conte announced that the country will deescalate into phase two. From May 4th, businesses such as catering services, manufacturing, construction, real estate, wholesale trade, and sports activities can resume operations. An additional $55 billion is pledged to support families, workers, and businesses struggling due to the pandemic. 

Meanwhile a new Swiss biosensor could be used to detect the COVID-19 virus, SARS-CoV-2, in public spaces like hospitals or train stations, Swiss authorities reported last Thursday. The biosensor, which was developed by the Swiss Federal Laboratories for Materials Science and Technology (EMPA) in collaboration with Zurich’s Federal Institute of Technology (ETHZ), can help contain outbreaks in public spaces by detecting ‘hotspots’ of viral genetic material floating in the air.

In the United States, the nursing home industry sought immunity from lawsuits after lawmakers  appealed to the CDC and CMS to disclose information on infections in nursing home facilities. Nursing homes have emerged as outbreak hotspots in most hard-hit countries. Hans Kluge, Regional Director for WHO Europe, told reporters last Thursday that almost half of the COVID-19 deaths across the WHO European region were in nursing homes.

In an interview with Financial Times, Bill Gates announced that the Bill and Melinda Gates Foundation (BGMF) would “almost entirely shift” to work on COVID-19 related problems, even in the non-health sectors such as education, where the Foundation has become involved in online learning.

Meanwhile, the CDC added six more symptoms to COVID-19, including chills, repeated shaking with chills, new loss of taste or smell, sore throat, headache, and muscle pain. 

In a video conference today with the Chief Ministers of the Indian states, Prime Minister Narendra Modi claimed that ‘the lockdown has yielded positive results’ and that ‘the country has managed to save thousands of lives in the past 1.5 months.’ 

Modi’s remarks coincide with the Indian Ministry of Health and Family Welfare’s new guidelines for home isolation of very mild/pre-symptomatic COVID-19 cases released today. The recommendations include mandating that caregivers and patients wear a triple-layered medical mask and disinfecting the used marks with 1% sodium hypo-chlorite solution before discarding.

Total cases of COVID-19 as of 6:31PM CET 27 April 2020, with active case distribution globally. COVID-19 cases exceed 3 million mark.

Tsering Lhamo and Svet Lustig Vijay contributed to this story.

Image Credits: University of Oxford/CEBM , Journal of Translational Medicine, WHO Clinical Trials Registry, captured by STAT News.

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