H5N1

WHO director predicts 100 million additional cases worldwide

Via The Washington Post: Coronavirus latest updates: WHO director predicts 100 million additional cases worldwide.

World Health Organization Director General Tedros Adhanom Ghebreyesus suggested Wednesday that unless things change, the world could see 100 million more cases of covid-19 by the early months of next year. 

“At the current trajectory, we could pass 300 million cases early next year,” he said during a media briefing. “But we can change that. We are all in this together, but the world is not acting like it.” 

The number of recorded covid-19 cases reached 200 million last week, just six months after the world passed 100 million cases, Tedros noted, “and we know that the real number of cases is much higher.” 

At the briefing, WHO officials emphasized that more research was being done on treatment for covid-19 in an unprecedented multicountry trial called Solidarity Plus, which will look at the effectiveness of three new drugs in 52 countries. 

Officials also said the spread of virulent variants such as delta would change assumptions about herd immunity and vaccination targets. 

“There’s no specific number or magic number that needs to be achieved. It's really related to how transmissible the virus is,” said Katherine O'Brien, director of the WHO's immunization department. 

“What’s been happening with coronavirus … is that as variants are emerging and are more transmissible, it does mean that a higher fraction of people need to be vaccinated to likely achieve some level of herd immunity,” O’Brien said.

Colchicine reduces the risk of COVID-19-related complications

A news release from the Montreal Heart Institute: Colchicine reduces the risk of COVID-19-related complications. Excerpt:

MONTREAL, January 22, 2021 – The Montreal Heart Institute (MHI) announced today that the COLCORONA clinical trial has provided clinically persuasive results of colchicine’s efficacy to treat COVID-19. The study results have shown that colchicine has reduced by 21% the risk of death or hospitalizations in patients with COVID-19 compared to placebo. 

This result obtained for the global study population of 4488 patients approached statistical significance. The analysis of the 4159 patients in whom the diagnosis of COVID-19 was proven by a naso-pharyngeal PCR test has shown that the use of colchicine was associated with statistically significant reductions in the risk of death or hospitalization compared to placebo. 

In these patients with a proven diagnosis of COVID-19, colchicine reduced hospitalizations by 25%, the need for mechanical ventilation by 50%, and deaths by 44%. This major scientific discovery makes colchicine the world’s first oral drug that could be used to treat non-hospitalized patients with COVID-19. 

“Our research shows the efficacy of colchicine treatment in preventing the ‘cytokine storm’ phenomenon and reducing the complications associated with COVID-19,” said Dr. Jean-Claude Tardif, Director of the MHI Research Center, Professor of Medicine at the Université de Montréal and Principal Investigator of the COLCORONA trial. “We are pleased to offer the first oral medication in the world whose use could have a significant impact on public health and potentially prevent COVID-19 complications for millions of patients.” 

Treating patients at risk of complications with colchicine as soon as the diagnosis of COVID-19 is confirmed by PCR reduces their risk of developing a severe form of the disease and, consequently, reduces the number of hospitalizations. Prescribing colchicine to patients could help alleviate the problems of hospital congestion and reduce healthcare costs here and around the world. 

“Our innovative research program also proves that the Montreal Heart Institute can make rapid scientific breakthroughs in a way that is economically viable for patients by repurposing existing drugs,” continued Dr. Jean-Claude Tardif.

Aspirin to be tested in UK as potential COVID-19 treatment

Via The Guardian: Aspirin to be tested in UK as potential coronavirus treatment | World news | The Guardian.

Thousands of coronavirus patients in Britain will be given aspirin as part of a trial to determine whether the painkiller can reduce the risk of dangerous blood clots.  

The cheap and widely available drug has been added to a list of potential treatments to be tested as part of the Randomised Evaluation of Covid-19 therapy (Recovery) trial, one of the biggest in Britain. 

People infected with coronavirus seem to have hyper-reactive platelets, the cell fragments that help stop bleeding, which means that they are at higher risk of potentially deadly blood clots, scientists say. 

Experts hope that aspirin, an anti-platelet agent which is commonly used as a blood thinner, can reduce the possibility of clotting complications.  

“Aspirin is widely used to prevent blood clots in many other conditions, including heart attack, stroke, and pre-eclampsia in pregnant women,” said Prof Martin Landray, co-chief investigator of the trial.  

“But enrolling patients in a randomised trial such as Recovery is the only way to assess whether there are clear benefits for patients with Covid-19 and whether those benefits outweigh any potential side-effects such as the risk of bleeding.”  

At least 2,000 patients are expected to get 150mg of aspirin daily along with the usual regimen. Data from those patients will be compared with at least 2,000 other patients who receive the standard Covid-19 treatment on its own.

WHO: Solidarity Therapeutics Trial produces conclusive evidence on the effectiveness of repurposed drugs for COVID-19 in record time

A WHO news release: Solidarity Therapeutics Trial produces conclusive evidence on the effectiveness of repurposed drugs for COVID-19 in record time. The full release, with my bolding:

In just six months, the world’s largest randomized control trial on COVID-19 therapeutics has generated conclusive evidence on the effectiveness of repurposed drugs for the treatment of COVID-19. 

Interim results from the Solidarity Therapeutics Trial, coordinated by the World Health Organization, indicate that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients. 

The study, which spans more than 30 countries, looked at the effects of these treatments on overall mortality, initiation of ventilation, and duration of hospital stay in hospitalized patients. Other uses of the drugs, for example in treatment of patients in the community or for prevention, would have to be examined using different trials.  

The progress achieved by the Solidarity Therapeutics Trial shows that large international trials are possible, even during a pandemic, and offer the promise of quickly and reliably answering critical public health questions concerning therapeutics. The results of the trial are under review for publication in a medical journal and have been uploaded as preprint at medRxiv available at this link: https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1 

The global platform of the Solidarity Trial is ready to rapidly evaluate promising new treatment options, with nearly 500 hospitals open as trial sites.  

Newer antiviral drugs, immunomodulators and anti-SARS COV-2 monoclonal antibodies are now being considered for evaluation. 

Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters

Via Nature Microbiology, good news for Syrian hamsters and maybe for humans as well: Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters. The absrract:

SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality. Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. 

Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. 

In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC50 = 0.69 µM) and DNA-unwinding (IC50 = 0.70 µM) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc(II) ions from the enzyme by bismuth(III) ions. 

Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth(III) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection.

This article in the South China Morning Post discusses the study.

Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19

Via JAMA Network: Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. The key points and abstract:

Key Points 

Question  In patients with coronavirus disease 2019 (COVID-19) and moderate or severe acute respiratory distress syndrome (ARDS), does intravenous dexamethasone plus standard care compared with standard care alone increase the number of days alive and free from mechanical ventilation? 

Findings  In this randomized clinical trial that included 299 patients, the number of days alive and free from mechanical ventilation during the first 28 days was significantly higher among patients treated with dexamethasone plus standard care when compared with standard care alone (6.6 days vs 4.0 days).  

Meaning  Intravenous dexamethasone plus standard care, compared with standard of care alone, resulted in a statistically significant increase in the number of days alive and free of mechanical ventilation over 28 days. 

Abstract 

Importance  Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients.  

Objective  To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19–associated ARDS. 

Design, Setting, and Participants  Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients.  

Interventions  Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). 

Main Outcomes and Measures  The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. 

Results  A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, −1.16; 95% CI, −1.94 to −0.38; P = .004). 

There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. 

Conclusions and Relevance  Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days.

Curing COVID-19

An editorial in The Lancet Infectious Diseases: Curing COVID-19.

As the COVID-19 pandemic moves into its 10th month, greater patient survival suggests that treatment of severe disease has improved. How much of this improvement is due to better supportive care and how much to pharmaceuticals is a matter of debate. Given the huge effort that the biomedical community has put into finding drugs to treat COVID-19, with thousands of trials completed and ongoing, it's worth taking stock of the evidence for what has worked and what has not. 

The hunt for COVID-19 treatments has become extraordinarily politicised, and no more so than with the aminoquinoline drugs chloroquine and hydroxychloroquine. Early observational studies suggested a beneficial effect of treatment with these cheap drugs, leading to acclamation by US President Trump. However, randomised controlled trials (RCTs) in hospitalised patients have shown no effect of hydroxychloroquine in reducing mortality. One RCT hinted at an effect when used as post-exposure prophylaxis, but this was not statistically significant. 

Unless new, high-quality evidence emerges, the aminoquinolines appear to have no future in the management of COVID-19. Remdesivir, an antiviral, was also the subject of White House fanfare. The US Government has attempted to corner the market for this costly drug but results of clinical trials are ambiguous. One review concluded that remdesivir may reduce time to clinical improvement and decrease mortality but had no effect on need for invasive ventilation or length of hospital stay. A subsequent RCT found no effect on mortality. Although approved to treat COVID-19 in the USA and Europe, conclusive evidence to support remdesivir is lacking. 

For other antivirals, there is no good evidence for efficacy of favipiravir, although it has been approved in Russia, and the lopinavir/ritonavir combination showed no clinical benefit in the UK RECOVERY RCT.  

Immunomodulators to treat COVID-19 are being widely tested in clinical trials. Among the front-runners, evidence to support use of tocilizumab, a monoclonal antibody against interleukin-6 receptors, comes largely from observational studies. Roche, the manufacturer, has announced that the drug did not improve clinical status in a phase 3 RCT among patients with severe COVID-19-associated pneumonia. Similarly, good quality evidence on the use of convalescent plasma is still awaited. 

Large RCTs such as RECOVERY, which includes tocilizumab and convalescent plasma groups, should provide answers. Immunomodulators that do work are the corticosteroids. In the dexamethasone group of RECOVERY, deaths were reduced by 35% in ventilated patients and by 20% among those receiving oxygen only compared with those in the standard care group. 

An RCT of dexamethasone done in Brazil further supports the beneficial effect of the drug. The REMAP-CAP RCT of hydrocortisone—another corticosteroid—versus placebo in patients with severe COVID-19 showed a 93% improvement in the intervention group in days when organ support was not needed. Based on these findings, WHO guidelines recommend corticosteroids in patients with severe and critical COVID-19. 

Is targeted treatment reducing deaths as the disease continues to sweep around the world? Where there has been a resurgence of COVID-19 cases to levels at least as high as when the pandemic first struck in the spring, such as in the USA, France, and Spain, it has not been followed by a comparable increase in deaths, nor of people requiring admission to hospital. Thus, treatment alone cannot be responsible for saving lives.

Possible explanations for the recent disparity in cases and deaths include more widespread testing, meaning that the number of cases being detected is closer to the true burden of infection, whereas the accuracy of counting deaths remains unchanged; lower viral load at the point of transmission, and hence less severe disease, because of non-pharmaceutical measures such as mask wearing; and changes in the distribution of cases towards younger age groups. 

Data from England show that until recently cases have been fairly evenly distributed across all ages from 20 years upwards, but by the last 2 weeks of August cases in people aged 20–39 were about ten times the number in those aged 70 or more. Risk of COVID-19 death in young people is tiny compared with the elderly. However, cases in the young might yet spill over into older people, and the long-term consequences of non-fatal disease are unknown. 

Whatever the reasons for apparent declining mortality, the impact of drug treatments on the COVID-19 pandemic is still limited. The massive research effort needs to bear fruit with a broader range of effective therapies.

COVID-19 live updates: Cases are surging along the US Gulf Coast

Via The New York Times, a grim afternoon roundup: Coronavirus Live Updates: Cases Are Surging Along the U.S. Gulf Coast. Click or tap through to read the stories listed in the bullet points:

Known cases surpassed four million in the United States. The White House and Senate Republicans neared agreement on a proposal for the next round of virus relief.  

RIGHT NOW Another study showing that a malaria drug that was heavily promoted — and even taken — by President Trump did not improve the conditions of patients with Covid-19 was published in the New England Journal of Medicine. 

Here’s what you need to know: 

• Texas and Florida have drawn attention, but the virus is surging in Alabama, Louisiana and Mississippi too. 

• The U.S. passes four million known cases, as hospitalizations and deaths rise. 

• Draft Republican virus aid proposal reflects significant retreat by White House on tax cuts, testing and schools. 

• U.S. testing continues to falter with more shortages in lab equipment. 

• Another study shows that the drug hydroxychloroquine didn’t help Covid-19 patients. 

• As Trump calls for schools to reopen fully for in-person instruction, his son’s school says it will not. 

• ‘Untrue and unacceptable’: Officials at the W.H.O. reject reported criticism from Pompeo.

Dr. Tedros on COVID-19: 'We have clearly not reached the peak of the pandemic'

WHO has published WHO Director-General's opening remarks at the media briefing on COVID-19 - 7 July 2020. Excerpt:

It took 12 weeks for the world to reach 400 thousand cases of COVID-19. 

Over the weekend, there were more than 400 thousand cases across the globe.  

There have now been 11.4 million cases of COVID-19 and more than 535,000 lives have been lost. 

The outbreak is accelerating and we have clearly not reached the peak of the pandemic.  

While the number of deaths appears to have levelled off globally, in reality some countries have made significant progress in reducing the number of deaths, while in other countries deaths are still on the rise. 

Where there has been progress in reducing deaths, countries have implemented targeted actions toward the most vulnerable groups, for example those people living in long-term care facilities. 

=== 

Over the past few months, there has been a lot of discussion about the origins of COVID-19. 

All preparations have been finalised and WHO experts will be traveling to China this weekend to prepare scientific plans with their Chinese counterparts for identifying the zoonotic source of the disease.   

The experts will develop the scope and terms of reference for a WHO-led international mission.  

The mission objective is to advance the understanding of animal hosts for COVID-19 and ascertain how the disease jumped between animals and humans.

===

WHO is deeply concerned about the impact of COVID-19 on the global response to HIV.

A new WHO survey showed access to HIV medicines has been significantly curtailed as a result of the pandemic.

73 countries have reported that they are at risk of stock-outs of antiretroviral medicines (ARVs).

To mitigate the impact of the pandemic on treatment access, WHO recommends all countries prescribe ARVs for longer periods of time.

Up to six months while supply chains for all medicines are fully functioning.

Similarly, shortages of condoms and pre-exposure prophylaxis can prove costly and WHO calls for countries to ensure uninterrupted prevention, testing and treatment services for HIV.

The disruptions in access to life-saving commodities and services come at a critical moment as progress in the global response to HIV stalls.

Over the last two years, numbers of new HIV infections stabilised at 1.7 million annually and there was only a modest reduction in AIDS-related deaths.

More than 25 million people now have access to ARVs but global targets for prevention, testing and treatment are off target.

Progress is stalling because HIV prevention and testing services are not reaching the groups that need them most.

Steroid found to help prevent deaths of sickest COVID-19 patients

Via The Guardian: Steroid found to help prevent deaths of sickest coronavirus patients.

A cheap steroid has become the first life-saving treatment in the Covid-19 pandemic, described by scientists as a major breakthrough and raising hopes for the survival of thousands of the most seriously ill.  

Dexamethasone is cheap, available from any pharmacy, and easily obtainable anywhere in the world. Investigators said the drug was responsible for the survival of one in eight of the sickest patients – those who were on ventilators – in the Recovery trial, the biggest randomised, controlled trial of coronavirus treatments in the world.  

“It is the only drug so far shown to reduce mortality and it reduces it significantly,” said Peter Horby, a professor of emerging infectious diseases in the Nuffield department of medicine, at the University of Oxford, and one of the chief investigators of the trial. “It is a major breakthrough, I think.” 

Prof Martin Landray, his co-chief investigator said the sickest patients could begin to be treated with the drug immediately. “The search has been on for a treatment that actually reduces the risk of dying. There hasn’t been one until today.  

“This is a drug that is globally available. This is not an expensive drug. That is immensely important.” 

A total of 2,104 patients were chosen at random to receive 6mg of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days, and were compared with 4,321 patients chosen at random to continue with normal care alone. Among the latter group of patients, 28-day mortality was highest in those who required ventilation (41%), intermediate in those who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).  

Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75; p=0.14). 

Based on these results, the use of dexamethasone would prevent one death of around eight ventilated patients, or one of about 25 patients requiring oxygen alone.  

Last week, the Recovery team, who have been trialling seven drugs and will add more, concluded that hydroxychloroquine did not benefit patients in hospital with Covid-19. 

Sir Patrick Vallance, the government’s chief scientific adviser, said: “This is tremendous news today from the Recovery trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine. 

“This is a ground-breaking development in our fight against the disease, and the speed at which researchers have progressed finding an effective treatment is truly remarkable. It shows the importance of doing high quality clinical trials and basing decisions on the results of those trials.”