H5N1

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.

COVID-19: Candidate vaccines in Cuba.

Via The BMJ, a letter dated November 30: Candidate Vaccines in Cuba.

Cuba has four vaccine candidates against Covid-19 in clinical trials, after the authorization of the study phase for Mambisa and Abdala, developed by the Center for Genetic Engineering and Biotechnology (CIGB).  

According to the information released on social networks, this Thursday the Medicines, Equipment and Medical Devices regulatory authority authorized the start of clinical trials of these last two vaccine candidates. 

The first of them, named Mambisa (CIGB 669), will be applied nasally; while the last, called Abdala (CIGB 66), will be administered intramuscularly.  

The drug CIGB 669 is a subunit vaccine that uses the AgnHB protein as an antigen, with the ability to stimulate the immune response at the mucosal level, the first barrier against a pathogen and in systemic behaviors.  

It was named Mambisa in tribute to the women who fought in the independence wars in the second half of the 19th century.  

The second of these candidates and the fourth from Cuba uses yeast as a receptor binding domain protein and alumina as an adjuvant. 

Named Abdala in homage to the first dramatic poem by the Cuban intellectual José Martí (1869), the study will aim to assess safety in a first stage.  

In the second stage, in addition to safety, the immune response capacity in a larger group of volunteers will be evaluated.  

Cuba was the first country in Latin America and the Caribbean, and the 30th worldwide, to receive authorization to begin clinical trials of a vaccine candidate against Covid-19 called Soberana 01, in August. 

At the beginning of November, the WHO included a second Cuban vaccine candidate (Soberana 02) on the official site of projects in phases of clinical trials against the disease.  

Both, developed by the Finlay Vaccine Institute, are on the list of 47 registered candidates worldwide and are moving positively in human clinical trials. 

In parallel, the CIGB was working on these other two projects against the pandemic. The investigation should conclude all its stages in January 2021 and be available to the population in February.

COVID-19 in Russia: The latest news, Dec. 13

Via The Moscow Times: Coronavirus in Russia: The Latest News | Dec, 13. Excerpt:

• Russia confirmed 28,080 coronavirus cases and 488 deaths. 

• Moscow municipal workers as well as residents working in the culture and service sectors will be able to receive Russia’s Sputnik V vaccine starting Monday, Mayor Sergei Sobyanin announced. The new “risk groups” were added to the eligibility list after Moscow was set to receive a new batch of the vaccine. 

• Moscow-based "R-Pharm" will become a leading manufacturer of Russia's Sputnik V coronavirus vaccine, the state-run Interfax news agency reported Friday citing Mayor Sergei Sobyanin. Working at full capacity, the factory will produce up to 10 million doses a month.  

• Russia’s state-run Gamaleya research center will partner with AstraZeneca to test in a clinical trial whether combining their jabs would boost immunity to Covid-19, the British drugmaker announced Friday. 

• Russia recorded more deaths in October than in any single month for more than a decade, official statistics published Thursday showed. Russia’s federal statistics agency (Rosstat) said 22,761 people with coronavirus died during the month, while the number of deaths was more than 47,000 — or 30% — higher than in 2019.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

Via NEJM: Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. The abstract and then another link:

BACKGROUND 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.  

METHODS 

In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.  

RESULTS 

A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. 

The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.  

CONCLUSIONS 

A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines.

See also this NEJM editorial on the implications of this study.

Why emergency COVID-19 vaccine approvals pose a dilemma for scientists

Via Nature.com: Why emergency COVID-vaccine approvals pose a dilemma for scientists. Excerpt:

After a flurry of positive results from clinical trials of COVID-19 vaccines, developers are now seeking ‘emergency use’ approvals, which could see these immunizations deployed in potentially tens of millions of people. But scientists are concerned that this kind of early deployment could compromise the ongoing clinical trials that seek to show conclusively how well the vaccines work.  

Following the release of early data from phase III trials on 9 November, vaccine makers Pfizer and BioNTech have sought regulatory permission to deploy their vaccine under emergency-use rules. The developer of another leading vaccine, Moderna, is expected to do the same within weeks.  

Once a vaccine is granted emergency approval, there is pressure on developers to offer the immunization to trial participants who received a placebo. But if too many people cross over to the vaccine group, the companies might not have enough data to establish long-term outcomes, such as safety, how long vaccine protection lasts and whether the jab prevents infection or just the disease.  

“It’s a real vaccine development dilemma,” says Klaus Stöhr, who formerly headed vaccine design at the pharmaceutical company Novartis in Cambridge, Massachusetts, and is now retired. Still, Stöhr thinks that the vaccine should be granted emergency use authorization because its effectiveness has been established and there is a dire need.

Pfizer’s early data shows COVID-19 vaccine is more than 90% effective

This is the morning's big story; at the moment, the Dow Jones is up over 1,200 points on the news. I hope we won't be disappointed. Via The New York Times: Pfizer’s Early Data Shows Coronavirus Vaccine Is More Than 90% Effective. Excerpt:

The drug maker Pfizer announced on Monday that an early analysis of its coronavirus vaccine trial suggested the vaccine was robustly effective in preventing Covid-19, a promising development as the world has waited anxiously for any positive news about a pandemic that has killed more than 1.2 million people.  

Pfizer, which developed the vaccine with the German drugmaker BioNTech, released only sparse details from its clinical trial, based on the first formal review of the data by an outside panel of experts.  

The company said that the analysis found that the vaccine was more than 90 percent effective in preventing the disease among trial volunteers who had no evidence of prior coronavirus infection. If the results hold up, that level of protection would put it on par with highly effective childhood vaccines for diseases such as measles. No serious safety concerns have been observed, the company said. 

Pfizer plans to ask the Food and Drug Administration for emergency authorization of the two-dose vaccine later this month, after it has collected the recommended two months of safety data. By the end of the year it will have manufactured enough doses to immunize 15 to 20 million people, company executives have said.  

“This is a historical moment,” Kathrin Jansen, a senior vice president and the head of vaccine research and development at Pfizer, said in an interview. “This was a devastating situation, a pandemic, and we have embarked on a path and a goal that nobody ever has achieved — to come up with a vaccine within a year.”  

Independent scientists have cautioned against hyping early results before long-term safety and efficacy data has been collected. And no one knows how long the vaccine’s protection might last. Still, the development makes Pfizer the first company to announce positive results from a late-stage vaccine trial, vaulting it to the front of a frenzied global race that began in January and has unfolded at record-breaking speed. 

Eleven vaccines are in late-stage trials, including four in the United States. Pfizer’s progress could bode well for Moderna’s vaccine, which uses similar technology. Moderna has said it could have early results later this month.

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.

What defines an efficacious COVID-19 vaccine?

Via The Lancet Infectious Diseases: What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. The summary:

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 1 million deaths in the first 6 months of the pandemic and huge economic and social upheaval internationally. An efficacious vaccine is essential to prevent further morbidity and mortality. 

Although some countries might deploy COVID-19 vaccines on the strength of safety and immunogenicity data alone, the goal of vaccine development is to gain direct evidence of vaccine efficacy in protecting humans against SARS-CoV-2 infection and COVID-19 so that manufacture of efficacious vaccines can be selectively upscaled. 

A candidate vaccine against SARS-CoV-2 might act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. However, the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials. 

In this Review, we explore the challenges in assessing the efficacy of candidate SARS-CoV-2 vaccines, discuss the caveats needed to interpret reported efficacy endpoints, and provide insight into answering the seemingly simple question, “Does this COVID-19 vaccine work?”

In depth: Who’s getting vaccinated? High-risk groups, students going abroad join China's growing trials

Via Caixin Global: In Depth: Who’s Getting Vaccinated? High-Risk Groups, Students Going Abroad Join China's Growing Trials. Excerpt:

China is expanding the number of people receiving its experimental Covid-19 vaccines. Two eastern cities are offering one to the general public, and a biotech company is providing another one free to students heading abroad, even though there are still uncertainties about their safety and effectiveness.  

The city of Jiaxing in Zhejiang province, south of Shanghai, is offering a vaccine under development by Beijing-based Sinovac Biotech, local health authorities said Thursday. The city, with a population of more than 4 million, said high-risk groups have already started to receive the vaccines. The shots will later be made available to the general public. 

Any residents with an urgent need for vaccination can consult community health centers, Jiaxing’s center for disease control and prevention (CDC) said in a statement on its official WeChat account. A person close to Sinovac told Caixin that Zhejiang bought 2 million doses of vaccines. Another city in Zhejiang province, Yiwu, is also offering walk-in Covid-19 vaccines to residents. The first batch of vaccinations was concluded at a community health center, Caixin learned. 

The programs represent a further expansion of Covid-19 vaccinations in China using experimental inoculations even as clinical trials are still underway to determine their safety and effectiveness. China has gained much greater control over the coronavirus pandemic than much of the rest of the world, where the disease continues raging. 

China officially launched its emergency-use program in July, but certain state-owned companies internally started having employees take the vaccine as early as June, workers told Caixin. Since then, hundreds of thousands of people have taken the experimental coronavirus vaccine, including employees of the vaccine developers, essential workers and people working abroad. 

Vaccines developed by Sinovac, China National Biotec Group (CNBG) and CanSino Biologics have been approved for emergency use. All three vaccines are still undergoing phase III trials to prove they are safe and effective. It isn’t yet known how long the inoculations may provide immunity to the coronavirus.  

Zheng Zhongwei, the National Health Commission official in charge of coronavirus vaccines, said in August that emergency use of the experimental vaccines should be limited to people within the prescribed scope, such as medical workers, pandemic response officials and border inspection agents. To prevent another outbreak in the fall and winter, it may be appropriate to expand the scope of emergency use to include essential workers such as grocery store staff, transportation workers and workers in the service sector, Zheng said.

Students heading overseas given priority

The expansion of emergency experimental vaccines to students has raised safety and ethical concerns. In addition, the process of gaining access to the inoculations seems haphazard and chaotic, according to interviews with students.

CNBG started accepting vaccination appointments in Beijing and Wuhan, according to media reports citing people familiar with the matter. People could make appointments by scanning a QR code or through a mini app link. They were to receive a vaccination notice at designated sites in about two weeks, and students seeking to study abroad would be given priority, the reports said.

As of Oct. 12, the mini app showed that more than 90,000 people requested vaccinations. An insider from CNBG said Oct. 13 that the media reports were not true, and that same day the mini app link couldn’t be opened, citing “system maintenance.”

Some students who plan to study abroad said they still received the vaccine through the mini app link, Caixin learned, even the day after the link stopped working. Student Li Yi (a pseudonym), said he received the CNBG vaccine Oct. 11 in Beijing.

“So many people have received the vaccine before the students, and they are fine,” Li said.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV

Via The Lancet Infectious Diseases: Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. The summary:

Background 

The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans. 

Methods 

We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18–80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18–59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 μg, 4 μg, or 8 μg on days 0 and 28. In phase 2, healthy adults (aged 18–59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 μg on day 0 or on a two-dose schedule of 4 μg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. 

The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459. 

Findings 

In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 μg [n=24], 4 μg [n=24], or 8 μg [n=24] for both age groups [18–59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18–59 years, one [4%] in the 2 μg group, one [4%] in the 4 μg group, and two [8%] in the 8 μg group; ≥60 years, one [4%] in the 8 μg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. 

Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18–59 years (87·7 [95% CI 64·9–118·6], 2 μg group; 211·2 [158·9–280·6], 4 μg group; and 228·7 [186·1–281·1], 8 μg group) and the group aged 60 years and older (80·7 [65·4–99·6], 2 μg group; 131·5 [108·2–159·7], 4 μg group; and 170·87 [133·0–219·5], 8 μg group) compared with the placebo group (2·0 [2·0–2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 μg on day 0 [n=84] or 4 μg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). 

At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 μg day 0; 18 [21%], 4 μg days 0 and 14; 15 [18%], 4 μg days 0 and 21; and ten [12%], 4 μg days 0 and 28). One placebo recipient in the 4 μg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 μg day 0; one [1%], 4 μg days 0 and 14; three [4%], 4 μg days 0 and 21; two [2%], 4 μg days 0 and 28). 

The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 μg days 0 and 14 (169·5, 95% CI 132·2–217·1), days 0 and 21 (282·7, 221·2–361·4), and days 0 and 28 (218·0, 181·8–261·3) schedules than the 8 μg day 0 schedule (14·7, 11·6–18·8; all p<0·001). 

Interpretation 

The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 μg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 μg dose or 4 μg dose on days 0 and 14.