H5N1

The dynamics of SARS-CoV-2 infectivity with changes in aerosol microenvironment

Via medRxiv: The dynamics of SARS-CoV-2 infectivity with changes in aerosol microenvironment. This is a preprint, not yet peer-reviewed. It's also the subject of a widely read article in The Guardian. The abstract and then a comment:

Understanding the factors that influence the airborne survival of viruses such as SARS-CoV-2 in aerosols is important for identifying routes of transmission and the value of various mitigation strategies for preventing transmission. We present measurements of the stability of SARS-CoV-2 in aerosol droplets (~5-10µm equilibrated radius) over timescales spanning from 5 seconds to 20 minutes using a novel instrument to probe survival in a small population of droplets (typically 5-10) containing ~1 virus/droplet. Measurements of airborne infectivity change are coupled with a detailed physicochemical analysis of the airborne droplets containing the virus.

A decrease in infectivity to ~10 % of the starting value was observable for SARS-CoV-2 over 20 minutes, with a large proportion of the loss occurring within the first 5 minutes after aerosolisation. The initial rate of infectivity loss was found to correlate with physical transformation of the equilibrating droplet; salts within the droplets crystallise at RHs below 50% leading to a near instant loss of infectivity in 50–60% of the virus. However, at 90% RH the droplet remains homogenous and aqueous, and the viral stability is sustained for the first 2 minutes, beyond which it decays to only 10% remaining infectious after 10 minutes. The loss of infectivity at high RH is consistent with an elevation in the pH of the droplets, caused by volatilisation of CO2 from bicarbonate buffer within the droplet. Three different variants of SARS-CoV-2 were compared and found to have a similar degree of airborne stability at both high and low RH.

This is of course a fascinating and encouraging finding. It suggests we might ease our way back to 2019 by greatly improving ventilation in homes, schools, and workplaces. But the study should have very close peer review and reproducibility. The "good news surprise," is a very persuasive sales technique, but it can be overwhelmed by buyer's remorse over bad news reality (and infection).

'In an ocean of ashes, islands of order': WHO's SARS-CoV-2 origin report

An editorial in The Lancet Infectious Diseases: “In an ocean of ashes, islands of order”: WHO's SARS-CoV-2 origin report.

The highly anticipated WHO report on the origin of SARS-CoV-2 was released on March 30. 34 international and Chinese multidisciplinary experts reviewed hundreds of thousands of items of epidemiological, clinical, and genomic data, some dating back to 2015, and the corresponding plausibility of four origin hypotheses: direct zoonotic spillover, zoonotic transmission via an intermediate host, importation via food in the cold chain, and accidental laboratory release. 

Although the report is preliminary overall, it concludes that the most likely route of SARS-CoV-2 emergence was from a bat lineage via an unidentified intermediate host with more frequent human contact, in which the progenitor virus might have been circulating undetected for decades. Nevertheless, according to WHO Director-General Tedros Adhanom Ghebreyesus, “all hypotheses remain on the table”. 

The report, or more accurately the work and organisation that produced it, has already been criticised for not going far enough, the methodology not being transparent enough, and being too late. Speculations have been made that the Chinese Government's close supervision of the process, from visa arrangements through data access to the physical whereabouts of the international team at all times, have precluded meaningful conclusions. 

Indeed, one wonders how much can truly be achieved by 17 individuals who spend 2 weeks in quarantine and 2 weeks at exclusively pre-arranged, chaperoned meetings? 14 WHO member states have already issued a statement calling for an independent, transparent investigation with full access to raw data, which were often not available. Critics also point towards the report's supposed legitimising of the cold-chain hypothesis advocated by Chinese state media that leaves open the possibility that the virus originated elsewhere. Still, because of ongoing tensions between political spheres of influence, an investigation led by a USA–EU consortium is unlikely to be as independent as it might like to appear. 

Across the Lancet journals, we remember the urgency and gravity with which Chinese scientists prepared the first papers describing COVID-19 to alert the world of the impending threat. Zoonotic transmission of pathogens has accompanied humanity throughout its existence and can happen anywhere, whereas the report shows that the cold-chain hypothesis is rather unlikely, on the basis of available data so far. WHO have been criticised for not holding China accountable but, as others have pointed out, its member states have given it practically no mandate to do so.

WHO needs much more time to find enough concrete evidence in the vast remnants of clues of an event that happened (at least) 16 months ago to identify the origin of SARS-CoV-2. The team has made many recommendations for further study. Granular mortality and burden data from respiratory diseases beyond Hubei province need to be provided for time-series analyses to better clarify whether there was widespread SARS-CoV-2 circulation before the initial outbreak in Wuhan. This should be paralleled by thorough contact-tracing and review of full clinical reports linked to public gatherings to identify missing links in transmission. 

More detailed reports of past weekly purchases of antipyretics and cold medicines should also be reviewed. Curiously, traditional Chinese remedies, which are increasingly prevalent in China and could have been used as first-line treatments for cold-like symptoms, were not considered by the WHO team. 

Indeed, the raw and full data for the first 174 COVID-19 cases need to be examined, along with any early suspected but discounted cases. It would be necessary to re-assess any such stored patient samples using standardised tests with proven performance that only became available later in the pandemic. The same applies to samples from early studies suggesting circulation of the virus in other countries in mid-2019. Blood banks are also an important potential source of serological data that could be explored. 

Finally, a much more thorough sweep of domestic and wild animal genomes (curated in a purpose-built database) across China and east Asian countries, where horseshoe bat, pangolin, and other species susceptible to SARS-CoV-2 live, is needed to pinpoint the intermediate host, if any. 

Whatever the truth, all sides would be better off if they engaged in less finger-pointing and a lot more cooperation towards a One Health approach to future investigations. Only then can order out of chaos be made.

COVID-19 vaccines in high-risk ethnic groups

Via The Lancet: COVID-19 vaccines in high-risk ethnic groups.

Black, Asian, and minority ethnic communities worldwide have a disproportionate risk of severe COVID-19. In the UK, as of May 19, 2020, 36% of critically ill patients with COVID-19 requiring intensive care were from Black, Asian, or minority ethnic groups.1 According to Public Health England, the mortality risk from COVID-19, after accounting for sex, age, deprivation score, and geographical region, is double in Bangladeshi people and up to 50% higher in Black and south Asian people compared with White British people. This finding contrasts with age-adjusted all-cause mortality from previous years, which was lower in Asian and Black people than in White British people. These data imply that COVID-19 has more serious effects in Black and Asian people. 

The ethnic groups most affected by COVID-19 are under-represented in the COVID-19 vaccine trial data published so far. Despite efforts to encourage participation from Black, Asian, and minority ethnic groups, of the 552 participants in the phase 2/3 Oxford–AstraZeneca trial (based in Southampton and Oxford, UK), only one participant was Black and 19 were Asian. Large-scale trials also have a smaller proportion of minority groups compared with the populations sampled (appendix).

Black, Asian, and minority ethnic individuals are under-represented in research. However, the ongoing pandemic necessitates that access to trials and vaccinations shifts from being equal to being equitable. Study recruitment and participation designs should improve diversity in ethnic groups to maximise the validity of results to the populations concerned. Age and sex are routinely considered in recruitment design—the same should now apply to ethnicity. 

In the context of a pandemic that has higher infection and mortality risks in certain ethnic groups, it is important that these specific groups are adequately represented in vaccine trials to evaluate both immunogenicity and efficacy.

Understanding COVID-19 origins will take years, says WHO team member

Via Reuters: Understanding COVID-19 origins will take years, says WHO team member. Excerpt:

WUHAN, China (Reuters) - A member of the World Health Organization-led team visiting the central Chinese city of Wuhan said he has been surprised by the complexity of getting to the origins of the COVID-19 pandemic and that years of research lay ahead. 

Dominic Dwyer, a microbiologist and infectious diseases expert, said the team in Wuhan had received the access it requested from Chinese authorities as it tries to understand the early days of the novel coronavirus outbreak first identified in Wuhan. 

“Everybody knows how it really exploded out of Huanan market in Wuhan, but the key is what was happening around that time and before,” Dwyer said. 

The origin of the coronavirus has become highly politicised following accusations that China was not transparent in its early handling of the outbreak. Beijing has pushed the idea that the virus could have originated elsewhere. 

Dwyer, an Australian specialist in HIV/AIDS who previously worked with the WHO during the SARS and avian flu outbreaks, said the “conundrum” of COVID-19 was that early asymptomatic carriers may not have known they had it. 

“It would be naive to think that we’re going to get virus zero,” Dwyer said. The early cases were identified in November, “but it’s just the bit beforehand that’s the very interesting part and the tricky part and the difficult part”. 

Dwyer echoed his teammate Peter Daszak, a zoologist and animal disease expert, in his emphasis on the difficulty of understanding the disease. 

“Even SARS, even Ebola, we have some good ideas, but no one knows,” Daszak told Reuters on Thursday. “HIV: we don’t know the exact circumstances.”

Yong: COVID-19 changed science forever

Via The Atlantic, Ed Yong has another must-read: COVID-19 Changed Science Forever. Excerpt:

in fall of 2019, exactly zero scientists were studying COVID‑19, because no one knew the disease existed. The coronavirus that causes it, SARS‑CoV‑2, had only recently jumped into humans and had been neither identified nor named. But by the end of March 2020, it had spread to more than 170 countries, sickened more than 750,000 people, and triggered the biggest pivot in the history of modern science. Thousands of researchers dropped whatever intellectual puzzles had previously consumed their curiosity and began working on the pandemic instead. In mere months, science became thoroughly COVID-ized. 

As of this writing, the biomedical library PubMed lists more than 74,000 COVID-related scientific papers—more than twice as many as there are about polio, measles, cholera, dengue, or other diseases that have plagued humanity for centuries. Only 9,700 Ebola-related papers have been published since its discovery in 1976; last year, at least one journal received more COVID‑19 papers than that for consideration. By September, the prestigious New England Journal of Medicine had received 30,000 submissions—16,000 more than in all of 2019. 

“All that difference is COVID‑19,” Eric Rubin, NEJM’s editor in chief, says. Francis Collins, the director of the National Institutes of Health, told me, “The way this has resulted in a shift in scientific priorities has been unprecedented.” 

Much like famous initiatives such as the Manhattan Project and the Apollo program, epidemics focus the energies of large groups of scientists. In the U.S., the influenza pandemic of 1918, the threat of malaria in the tropical battlegrounds of World War II, and the rise of polio in the postwar years all triggered large pivots. Recent epidemics of Ebola and Zika each prompted a temporary burst of funding and publications. But “nothing in history was even close to the level of pivoting that’s happening right now,” Madhukar Pai of McGill University told me.

Why Nature needs to cover politics now more than ever

In Nature, an editorial published on October 6: Why Nature needs to cover politics now more than ever. Excerpt (and by all means read the whole thing):

Since Nature’s earliest issues, we have been publishing news, commentary and primary research on science and politics. But why does a journal of science need to cover politics? It’s an important question that readers often ask.  

This week, Nature reporters outline what the impact on science might be if Joe Biden wins the US presidential election on 3 November, and chronicle President Donald Trump’s troubled legacy for science. We plan to increase politics coverage from around the world, and to publish more primary research in political science and related fields. 

Science and politics have always depended on each other. The decisions and actions of politicians affect research funding and research-policy priorities. At the same time, science and research inform and shape a spectrum of public policies, from environmental protection to data ethics. The actions of politicians affect the higher-education environment, too. They can ensure that academic freedom is upheld, and commit institutions to work harder to protect equality, diversity and inclusion, and to give more space to voices from previously marginalized communities. However, politicians also have the power to pass laws that do the opposite. 

The coronavirus pandemic, which has taken more than one million lives so far, has propelled the science–politics relationship into the public arena as never before, and highlighted some serious problems. COVID-related research is being produced at a rate unprecedented for an infectious disease, and there is, rightly, intense worldwide interest in how political leaders are using science to guide their decisions — and how some are misunderstanding, misusing or suppressing it. And there is much interest in the fluctuating relationship between politicians and the scientists who governments consult or employ. 

Scholarly autonomy under threat 

Perhaps even more troubling are signs that politicians are pushing back against the principle of protecting scholarly autonomy, or academic freedom. This principle, which has existed for centuries — including in previous civilizations — sits at the heart of modern science. 

Today, this principle is taken to mean that researchers who access public funding for their work can expect no — or very limited — interference from politicians in the conduct of their science, or in the eventual conclusions at which they arrive. And that, when politicians and officials seek advice or information from researchers, it is on the understanding that they do not get to dictate the answers. This is the basis for today’s covenant between science and politics, and it applies across a range of research, education, public-policy and regulatory domains. 

It is not a perfect system by any means. Some research areas are more autonomous than others, and autonomy can never be a blank cheque: researchers must also be held accountable for their actions, and standards of quality and integrity must be upheld. But protection for autonomy is a long-standing benchmark, the standard to which experts and policymakers aspire. It requires a degree of trust between researcher and politician that each will keep to their word. And when this trust starts to ebb away, the system, too, begins to look vulnerable.  

That trust is now under considerable pressure around the world. Cracks have been evident for years in the field of climate change, with a number of politicians ignoring or seeking to undermine the irrefutable evidence showing that humans are the cause. But this lack of trust can now also be seen in other public domains in which verifiable knowledge and research are needed for effective policy-making.

Interference in scientific research on COVID-19 in Turkey

A letter in The Lancet: Interference in scientific research on COVID-19 in Turkey.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as it was later named, was first identified in Wuhan, China, on Jan 7, 2020. Over the following months, the virus rapidly spread throughout the world. The disease, COVID-19, was characterised as a pandemic by WHO on March 11, 2020. On the same day, the Turkish Ministry of Health reported the first case in Turkey. 

According to the Global Initiative on Sharing All Influenza Data platform, which analyses the genomic epidemiology of SARS-CoV-2, the disease reached Turkey mainly through Iran, with whom Turkey has strong commercial and touristic ties, and Saudi Arabia, where thousands of Turkish citizens travelled to visit the holy places until mid-March, 2020. 2 months after the first case, on May 11, 2020, the Turkish Ministry of Health declared that the number of COVID-19 cases had reached 139 771, with 3841 deaths. 

However, the excess mortality for Istanbul alone during this period was 4209 deaths. From 2016–19, the average number of deaths that occurred in Istanbul was 23 232 for the period of March 11 to July 5. In 2020, this figure went up to 27 955 deaths. The excess mortality found between March 11 and July 5, 2020, in Istanbul was 4723 deaths. There were at least 1952 unexplained deaths. However, the officially reported COVID-19 mortality in the same period was 2771 deaths.  

Because no other serious mass health events were recorded at that time, this discrepancy could be explained by non-compliance with WHO codes from the International Classification of Diseases (tenth edition). The official reporting system of Turkey only covered PCR-positive cases. As of July 27, 2020, Turkey ranks fourth in the European region for cases of COVID-19, with a total number of 225 173 patients and 5596 COVID-19 deaths, as reported by the Ministry of Health on the basis of PCR-positive cases alone. 

The establishment of a scientific board and full coverage of treatment, and the encouragement of research by the Ministry of Health and funding bodies such as the Scientific and Technological Research Council of Turkey and the Health Institutes of Turkey were admirable steps taken by the authorities in the beginning of the pandemic. However, tension soon started building among the public sector and medical and scientific organisations due to the Ministry of Health's lack of transparency, its reluctance to share basic data, and its refusal to collaborate. There were also concerns about the shortage of personal protective equipment for health-care workers. 

The final stroke came with the control of COVID-19 research by the Ministry of Health. Despite the great interest in research on COVID-19 in Turkey by researchers and physicians, the Turkish Ministry of Health announced a mandatory application for permission for research on COVID-19, before any application is made to ethics committees. This unprecedented decision was against the Constitution and laws regulating research activities in Turkey. It appears that most submitted projects have been approved by the Ministry of Health, but some projects, including a large, multicentre observational study by the Turkish Thoracic Society, have been rejected without any clear explanation. 

The regular procedure for research activities in Turkey is well defined. In keeping with the international regulations, researchers must get approval from the independent ethics committee. The Turkish Constitution clearly states that “everyone can learn science and art freely and has the right to teach, explain, disseminate and research in these areas”. The Science Academy, a member of the International Science Council, has highlighted this fact. The Turkish Medical Association and other professional medical organisations made a declaration through a press conference and urged the Ministry of Health to cancel their decision. 

In conclusion, we, as respiratory physicians and scientists, are worried about the restrictions imposed by the Turkish Ministry of Health on independent research about the COVID-19 pandemic in Turkey, and we sincerely hope that the Ministry of Health's decision will be taken back in compliance with the Turkish Constitution.

China’s COVID-19 vaccines are leaping ahead – but face challenges as virus wanes

Via Nature.com: China’s coronavirus vaccines are leaping ahead – but face challenges as virus wanes. Excerpt:

Chinese companies are at the forefront of global efforts to create a vaccine for the coronavirus, with more than half a dozen candidates in clinical development. Last week, Tianjin-based CanSino Biologics published results1 from an early-stage clinical trial showing that its vaccine is safe and can trigger an immune response.  

Yet the companies could face difficulty as they try to push vaccines through phase III trials, a crucial stage of testing that is needed to prove efficacy and secure approval from regulators. These trials usually require tens of thousands of participants, and with the outbreak in China largely under control, companies are having to test their vaccines elsewhere. But researchers say they might still struggle to enrol so many participants and employ enough health-care professionals to collect data.

“The Chinese companies will need to step outside of China,” says Jerome Kim, director-general of the International Vaccine Institute in Seoul. “The race is on,” he says, “and it’s really about who can set up in a high-risk area most quickly.” 

Chinese vaccine-makers will face other challenges, too. Vaccines will probably face extra scrutiny, given the country’s opaque regulatory system and previous vaccine scandals, say scientists. In 2018, hundreds of thousands of children reportedly received defective diptheria, tetanus and whooping cough vaccines.  

Quick to act 

As the country where the coronavirus outbreak began, China was fast out of the gate in developing vaccines. CanSino’s offering is made from a common-cold virus, tweaked to mimic the coronavirus. Sinopharm, a state-owned pharmaceutical company in Beijing, is developing two vaccines made using particles of the coronavirus that have been inactivated so that they can no longer cause disease. The company said in press releases in June that both vaccines had produced antibodies in all participants in preliminary phase I and II trials. And Beijing-based company Sinovac has announced similarly promising results for its own inactivated-virus vaccine.  

This month, Sinovac launched a phase III trial of its vaccine in Brazil. Sinopharm will be testing its inactivated vaccines in the United Arab Emirates (UAE). Only three other coronavirus vaccines have entered phase III trials: one produced by biotech company Moderna in Cambridge, Massachusetts; one by the University of Oxford and drug maker AstraZeneca, based in Cambridge, UK; and one by biotech company BioNTech of Mainz, Germany, in collaboration with New York City-based drug firm Pfizer.  

CanSino is also poised to launch a phase III trial. But the Chinese government has already said that its vaccine can be used by the military — making CanSino the first company to have a vaccine for COVID-19 approved for limited use in people. China has worked hard “to generate an efficient vaccine as soon as possible and to be transparent” when doing so, says Stéphane Paul, a vaccine researcher at the University of Lyon in France.  

The speed with which Chinese vaccine-makers are moving has raised hopes around the world. Sinopharm has even promised to have a vaccine ready to distribute by the end of the year.

The long game of COVID-19 research

Via The New Yorker, an important article by Jerome Groopman: The Long Game of Coronavirus Research. Excerpt:

Last month, Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, spoke at a biotech conference, where he emphasized how much is still unknown about the coronavirus. 

“I thought H.I.V. was a complicated disease,” he said. “It’s really simple compared to what’s going on with covid-19.” T

o anyone who knows the history of aids research—Fauci has spent much of his career studying the disease—this was a dismaying thing to hear. In 1984, President Reagan’s Health and Human Services Secretary, Margaret Heckler, said, “We hope to have a vaccine ready for testing in about two years.” Almost four decades later, there is still no vaccine. 

If Heckler’s words now seem like wishful thinking, the Trump Administration has worried scientists and physicians with what may prove to be a similar overpromise. In May, it unveiled a plan to deliver “hundreds of millions of doses” of a COVID-19 vaccine by the end of this year. The plan’s name—Operation Warp Speed—is meant to spark hope. But, in science, true hope is clear-eyed and brings a tight focus on the barriers and potential setbacks that exist along the path to desired results. 

In the face of a crisis as urgent as COVID-19, speed is desirable, and the worldwide mobilization to conquer the virus has been inspiring. But what Fauci said illustrates why it’s a grave mistake to favor speed at the cost of rigor. Quite simply, this is a disease that we are only beginning to understand: since the outbreak began, it has become evident that its effects are, like those of aids, astonishingly diverse and complex. 

Still largely thought of as a respiratory disease—it can indeed inflict devastating damage to the lungs—it is actually, as Fauci noted, capable of roving throughout the body. There are cases in which it causes kidney failure, stroke, or a so-called cytokine storm, an overreaction of the body’s immune system that can lead to multiple organ failure. In children, infection can lead to multisystem inflammatory syndrome, a condition that can damage the heart and other vital organs. COVID-19 has a startling spectrum of severity—from no symptoms to death—depending on a host of poorly understood factors. 

Fauci also pointed out another unknown: whether some survivors, especially those with the severest symptoms, would end up dealing with lifelong debilitating effects. Currently, we are not even sure how to assess protective immunity if we had a vaccine in hand—whether protection would be broad among all age groups and encompass the healthy as well as those whose clinical conditions, such as diabetes, heart disease, and obesity, predispose them to COVID-19. 

Even more worrying, for those who imagine a vaccine might end the pandemic like turning off a light switch, a number of recent studies suggest that people who’ve had the disease may not emerge with robust, lasting immunity. If so, it’s possible that the initial protection offered by a successful vaccine would similarly wane, and people could be infected again.

Russian state-sponsored hackers target Covid-19 vaccine researchers

Via The Guardian: Russian state-sponsored hackers target Covid-19 vaccine researchers. Excerpt:

Russian state-sponsored hackers are targeting UK, US and Canadian organisations involved in developing a coronavirus vaccine, according to British security officials. 

The UK’s National Cyber Security Centre (NCSC) said drug companies and research groups were being targeted by a group known as APT29, which was “almost certainly” part of the Kremlin’s intelligence services.  

British officials would not say if any of the attacks had been successful in their goal of stealing medical secrets. They stressed, however, that none of the vaccine research had been compromised as a result. 

Britain is at the forefront of research efforts to produce a coronavirus vaccine, with scientists at Oxford University and Imperial College London, among those leading global efforts to find the vital medicine.  

It is rare for the UK to explicitly state that it believes another country is behind a coordinated campaign of cyber-attacks, but British officials indicated it shared its assessment with the US and Canada, both of whom are expected to release their own updates shortly.  

The UK’s foreign secretary, Dominic Raab, said it was “completely unacceptable” for Russian intelligence services to target research on the Covid-19 pandemic.  

He said: “While others pursue their selfish interests with reckless behaviour, the UK and its allies are getting on with the hard work of finding a vaccine and protecting global health. The UK will continue to counter those conducting such cyber attacks, and work with our allies to hold perpetrators to account.” 

The APT29 group has been active for several years, and is also known in the hacker community as the Dukes or Cozy Bear. The same group has been linked to attacks on the US Democratic party in the run-up to 2016 elections. 

Cozy Bear came to prominence in 2015, when researchers at Kaspersky Lab pinned devastating hacks of the unclassified state department and White House networks on to the group. It has previously been alleged that this group is controlled by the Russian FSB spy agency.