Covid antiviral pills: What scientists still want to know

‘Drugs such as molnupiravir and Paxlovid could change the course of the pandemic if clinical trial results hold up in the real world...

‘Researchers will be looking at the ages and ethnicities of those who were enrolled in the trials, and at any other health conditions that they had, says John Mellors, an infectious-disease specialist at the University of Pittsburgh Medical Center in Pennsylvania.

‘Because antiviral drugs often need to be given early in the course of an infection for them to work effectively, Mellors will also be looking for more detail about when the drugs were given in the trials, and at how those timings correlated with efficacy. That information will provide a sense of when the window of opportunity for treatment closes. Neither trial had enough participants to enable firm conclusions to be drawn about the drugs’ ability to prevent deaths, but no deaths occurred in their treatment arms.

‘Researchers are also keen for any clue — including from further clinical trials — as to whether the drugs affect transmission of the coronavirus, or prevent illness in people who have been exposed to it.

‘If they do, the combination of vaccines and antiviral drugs could become a powerful tool in controlling outbreaks, says Jerome Kim, director-general of the International Vaccine Institute in Seoul. For example, if a worrying coronavirus variant emerges in a specific region, those who are most likely to be affected could be given an antiviral drug to supplement immunity from vaccines. This could clamp down on the virus and prevent its spread. “It opens up some new possibilities for the way we think about control,” Kim says. “This would have a really dramatic impact.”

Read here (Nature, Nov 10, 2021)

Leader of WHO’s new pandemic hub: Improve data flow to extinguish outbreaks

Former Nigeria CDC leader Chikwe Ihekweazu talks with Nature about the COVID crisis, and strengthening global response to future public-health emergencies...

What are the biggest problems you hope to fix — and why do you want to solve them at the WHO?

‘I want to make the mechanics of reporting disease-related information easier, and also demonstrate that the WHO can use that data to help countries that share it. One way to do that is to enable countries to derive value from their own data.

‘I wouldn’t want to do this at a venue other than the WHO. I know that different countries are creating hubs, as are some big donors. They may be able to analyse publicly available data, but they won’t have the same access to information from countries that the WHO does. Speaking as the current director of the Nigeria CDC, I can tell you that I wouldn’t share my data openly with a hub located in another country. We share our data with the WHO without worry because the WHO belongs to us and other countries as a member-state organization, and has a mandate from countries to monitor health risks and coordinate the response in health emergencies.’

Read here (Nature, Sept 21, 2021)

The fight to manufacture Covid vaccines in lower-income countries

‘Instead of holding out for today’s popular vaccines, some researchers hope that those in clinical trials will be easier to license and make in the global south. At the top of the list are protein-subunit vaccines, in which peptides matching those from SARS-CoV-2 teach the immune system to recognize the virus and fight it off. Researchers say the benefit of such vaccines is that vats of yeast or insect cells can churn out huge quantities of peptides, making the vaccines scalable. They add that many companies are familiar with the process because they produce vaccines for other diseases and recombinant drugs in a similar fashion.’

Read here (Nature, Sept 15, 2021)

India’s DNA Covid vaccine is a world first – more are coming

‘India has approved a new COVID-19 vaccine that uses circular strands of DNA to prime the immune system against the virus SARS-CoV-2. Researchers have welcomed news of the first DNA vaccine for people to receive approval anywhere in the world, and say many other DNA vaccines might soon be hot on its heels.

‘ZyCoV-D, which is administered into the skin without an injection, has been found to be 67% protective against symptomatic COVID-19 in clinical trials, and will probably start to be administered in India this month. Although the efficacy is not particularly high compared to that of many other COVID-19 vaccines, the fact that it is a DNA vaccine is significant, say researchers.

‘It is proof of the principle that DNA vaccines work and can help in controlling the pandemic, says Peter Richmond, a paediatric immunologist at the University of Western Australia in Perth. “This is a really important step forward in the fight to defeat COVID-19 globally, because it demonstrates that we have another class of vaccines that we can use.”

Read here (Nature, Sept 2, 2021)

How the Delta variant achieves its ultrafast spread

‘Viral load is roughly 1,000 times higher in people infected with the Delta variant than those infected with the original coronavirus strain, according to a study in China...

‘The combination of a high number of viruses and a short incubation period makes sense as an explanation for Delta’s heightened transmissibility, says epidemiologist Benjamin Cowling at the University of Hong Kong. The sheer amount of virus in the respiratory tract means that superspreading events are likely to infect even more people, and that people might begin spreading the virus earlier after they become infected.

‘And the short incubation makes contact tracing more difficult in countries such as China, which systematically tracks each infected person’s contacts and require them to quarantine. “Putting it all together, Delta’s really difficult to stop,” Cowling says.’

Read here (Nature, July 21, 2021)

Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

‘The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.’

Read here (Nature, Apr 16, 2021)

The race for antiviral drugs to beat Covid — and the next pandemic

‘Despite dire warnings, a stockpile of ready compounds to fight viral pandemics was sorely lacking. Can drugmakers finally do the right thing?...

“What we will hopefully find”, he [Alejandro Chavez, a bioengineer and antiviral drug researcher at Columbia University Irving Medical Center in New York City] says, “are inhibitors that work on, if you’re really lucky, an entire family.” That would make the best-case scenario a pan-coronavirus inhibitor. But a more reasonable goal might be developing a drug for a subset of coronaviruses, such as alphacoronaviruses, which currently cause non-lethal infections in humans, and having a different drug for betacoronaviruses, the group responsible for SARS, MERS, and COVID-19.

‘Once the viral lineage is identified, “the same principles of drug discovery apply”, says Marnix Van Loock, head of emerging pathogens at Johnson & Johnson’s global public-health unit in Beerse, Belgium. As he explains, researchers need to find ‘druggable pockets’ on the surface of essential enzymes that are conserved between related viruses and can be used to design active molecules.’

Read here (Nature, Apr 14, 2021)

What it will take to vaccinate the world against Covid-19

‘A special report outlines the challenges — from unleashing the power of mRNA vaccines, to the battle for temporary relief on intellectual-property rights...

‘In the long term, argues Friede, every region needs a facility that fully owns the production know-how and can produce vaccines. The gap is most egregious in Africa, a continent that imports 99% of its vaccines, says Nkengasong. It has only three big vaccine manufacturers. “Can a continent of 1.2 billion — projected to be 2.4 billion in 30 years, where one in four people in the world will be African — continue to import 99% of its vaccines?” Nkengasong asks.’

Read here (Nature, Mar 25, 2021)

Covid-19 recovery: Science isn’t enough to save us (Nature publication, Mar 23, 2020)

‘Policymakers sometimes talk about science as if it has superhero powers. When it comes to COVID-19, they often sound as though they hope vaccines will bring life back to how things were before. There will be no such luxury.

‘One key issue is who is being called on to aid recovery. Governments have sought expert advice from the beginning of the pandemic, but that expertise tended to come from people in science, technology, engineering and maths (STEM) — despite it being clear from the start that human behaviour, motivations and culture were key to an effective response. There are more than 80 people who have sat on the UK Scientific Advisory Group for Emergencies — yet only a narrow range of social scientists, and a single person representing the humanities, are included.

‘This approach needs to change. Science gave us vaccines, but SHAPE (social sciences, humanities and the arts for people and the economy) disciplines help us get to social realities, such as vaccine hesitancy. Humanity’s insight is more robust when STEM and SHAPE come together.’

Read here (Nature publication, Mar 23, 2020)

Rare Covid reactions might hold key to variant-proof vaccines

 ‘Some people mount an immune response able to fend off a menagerie of coronavirus variants...

‘Some of the vaccines that have been administered to millions of people might already be triggering variant-resilient immune responses. In another March preprint, a long-running COVID-19 study in Seattle, Washington, reported that after receiving a single dose of an mRNA vaccine, participants who had previously been infected with SARS-CoV-2 produced heaps of antibodies that can neutralize B.1.351, as well as an earlier circulating variant8. Those people also produced much higher levels of antibodies than typically seen even in those who have received two vaccine doses.

‘Leonidas Stamatatos, an immunologist at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle who co-led the study, suspects that a single vaccine dose boosted the levels of pre-existing antibodies that were capable of recognizing diverse variants. It’s not clear how to mimic this response in people who haven’t had COVID-19. One possibility is that a lag of several months between infection and vaccination was responsible, and that its effect could be replicated with another vaccine dose, given six months or a year after the first two, says Andy McGuire, an FHCRC immunologist who co-led the study.’

Read here (Nature, March 19, 2021)

Five reasons why Covid herd immunity is probably impossible

As Covid-19 vaccination rates pick up around the world, people have reasonably begun to ask: how much longer will this pandemic last? It’s an issue surrounded with uncertainties. But the once-popular idea that enough people will eventually gain immunity to SARS-CoV-2 to block most transmission — a ‘herd-immunity threshold’ — is starting to look unlikely.

• It’s unclear whether vaccines prevent transmission
• Vaccine roll-out is uneven
• New variants change the herd-immunity equation
• Immunity might not last forever
• Vaccines might change human behaviour

Read here (Nature, March 18, 2021) 

Multitude of coronavirus variants found in the US — but the threat is unclear

‘For the scientists who have spent the past year poring over hundreds of thousands of coronavirus genomes, the United States has been an enigma. Despite having world-leading genome sequencing infrastructure and experiencing more COVID infections than any other country, the United States has until recently lagged far behind in sequencing coronavirus genomes and spotting worrisome variants.

‘But in recent weeks, US researchers have identified a host of new variants, including in California, New York State, Louisiana and elsewhere. And they are continuing to ramp up SARS-CoV-2 sequencing efforts.

‘That has brought another challenge: making sense of the variants that are discovered. They carry potentially worrying mutations and might be becoming more common, but a dearth of data on how the variants are spreading means the threat they pose is unclear.’

Read here (Nature, Mar 6, 2021)

The search for animals harbouring coronavirus — and why it matters

‘Ever since the coronavirus started spreading around the world, scientists have worried that it could leap from people into wild animals. If so, it might lurk in various species, possibly mutate and then resurge in humans even after the pandemic has subsided.

‘That would bring the tale of SARS-CoV-2 full circle, because wild animals probably brought it to humans in the first place. Strong evidence suggests that the virus originated in horseshoe bats (Rhinolophus spp.), possibly hitching a ride on other animals before infecting people1. In the current stage of the pandemic, with hundreds of thousands of confirmed COVID-19 infections every day, people are still driving transmission of SARS-CoV-2. But years from now, when community spread has been suppressed, a reservoir of SARS-CoV-2 in free-roaming animals could become a recalcitrant source of new flare-ups.’

Read here (Nature, Mar 2, 2021)

Where did Covid come from? Five mysteries that remain

‘In the wake of the World Health Organization’s investigation, there are still key questions about when, where and how the pandemic began.

1. Was the virus circulating in Wuhan before the first known cases?
2. Was the virus spreading in people outside China before December 2019?
3. What was the role of the Huanan market?
4. Did frozen wild-animal meat have a role in the early spread of the virus?
5. Was the virus circulating in animals in China before the pandemic?

Read here (Nature, Feb 26, 2021)

Why Covid vaccines are so difficult to compare

‘Given the demand for speed amid limited supplies, any effort to rank the vaccines must take into account not only their reported effectiveness, but also supplies, costs, the logistics of deploying them, the durability of the protection they offer and their ability to fend off emerging viral variants. Even so, many people might find it hard to look away from clinical-trial results that suggest an efficacy gap. So far, more than 200 million doses of coronavirus vaccines have been delivered, and data have been rolling in from clinical trials in several countries. The top-line results from those studies suggest a range of protection: from 95% efficacy for a vaccine made by Pfizer of New York City and BioNTech of Mainz, Germany, to about 70% suggested by initial results on a vaccine made by AstraZeneca of Cambridge and the University of Oxford, both in the United Kingdom.’

Read here (Nature, Feb 23, 2021)

Can Covid vaccines stop transmission? Scientists race to find answers

‘Controlling the pandemic will require shots that prevent viral spread, but that feature is difficult to measure...

‘Preliminary analyses suggest that at least some vaccines are likely to have a transmission-blocking effect. But confirming that effect — and how strong it will be — is tricky because a drop in infections in a given region might be explained by other factors, such as lockdowns and behaviour changes. Not only that, the virus can spread from asymptomatic carriers, which makes it hard to detect those infections.

“These are among the hardest types of studies to do,” says Marc Lipsitch, an infectious-disease epidemiologist at the Harvard T. H. Chan School of Public Health in Boston, Massachusetts. “All of us are out there, hungrily trying to see what we can get out of little bits of data that do come out,” he says. Results from some studies are expected in the next few weeks.’

Read here (Nature, Feb 19, 2021)

The coronavirus is here to stay — here’s what that means

‘In January, Nature asked more than 100 immunologists, infectious-disease researchers and virologists working on the coronavirus whether it could be eradicated. Almost 90% of respondents think that the coronavirus will become endemic — meaning that it will continue to circulate in pockets of the global population for years to come (see 'Endemic future')...

‘More than one-third of the respondents to Nature’s survey thought that it would be possible to eliminate SARS-CoV-2 from some regions while it continued to circulate in others. In zero-COVID regions there would be a continual risk of disease outbreaks, but they could be quenched quickly by herd immunity if most people had been vaccinated.’ 

Read here (Nature, Feb 16, 2021)

Trust in Covid vaccines is growing

‘Attitudes towards COVID-19 vaccines seem to be improving in some parts of the world, a survey of thousands of people in 15 countries has found. Researchers have welcomed the results, which suggest that an increasing proportion of people are willing to be immunized. But they caution that some problems persist, such as concerns about vaccine safety. “For the first time since the pandemic began, I can sense that optimism is spreading faster than the virus,” says behavioural scientist Sarah Jones at Imperial College London, who co-led the global attitudes towards a COVID-19 vaccine survey.

‘The survey is part of the COVID-19 behaviour tracker, run by Imperial together with the UK market-research company YouGov.’

Read here (Nature, Feb 10, 2021)

Vaccines are curbing Covid: Data from Israel show drop in infections

‘Close to 90% of people aged 60 and older in the country have received their first dose of Pfizer’s 2-dose vaccine so far. Now, data collected by Israel’s Ministry of Health show that there was a 41% drop in confirmed COVID-19 infections in that age group, and a 31% drop in hospitalizations from mid-January to early February. In comparison, for people aged 59 and younger — of which just more than 30% have been vaccinated — cases dropped by only 12% and hospitalizations by 5% over the same time. The figures are based on analysis of roughly a quarter of a million COVID-19 infections.’

Read here (Nature, Feb 5, 2021)

Could mixing Covid vaccines boost immune response?

‘Vaccine developers often combine two vaccines to combat the same pathogen, and researchers are keen to deploy the strategy — known as a heterologous prime-boost — against the coronavirus. A heterologous prime-boost combination was approved last year by European regulators to protect against Ebola, and experimental HIV vaccines often rely on the strategy, says Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, Massachusetts. But it has yet to be tested for vaccines against COVID-19, which are typically given as a repeat injection of the same vaccine.

‘The ability to mix and match vaccines could make vaccination programmes more flexible: it would speed up the process and reduce the impact of any supply-chain disruptions. “It really makes the implementation much more simple,” said Mary Ramsay, head of immunization at Public Health England, at a press briefing on 3 February.’

Read here (Nature, Feb 4, 2021)