Covid-19: why the lab leak theory must be formally investigated

A year and a half into the pandemic, we still do not know exactly where the SARS-CoV-2 virus, which causes Covid-19, came from. The prevailing view so far has been that the virus “spilled over” from bats into humans. But there are increasing calls to investigate the possibility that it emerged from a lab in Wuhan, China, where Covid first appeared at the end of 2019.

So what do we know for sure, and what do we need still to find out?

We know the sequence of the SARS-CoV-2 virus is close to that of bat coronaviruses. Several decades ago its “ancestor” was circulating in bat populations in southern Asia.

But there are still many unanswered questions: we don’t know how the virus arrived in Wuhan, how its sequence evolved to allow human infection, and under what conditions it infected the first people who crossed its path. And for each of these stages, we don’t know whether there was a human contribution (direct or indirect).

Lire cet article en français: “Origine de la Covid-19 : l’hypothèse de l’accident de laboratoire doit-elle être étudiée d’un point de vue scientifique ?”

Zoonotic transmission pathways, in other words the passage of viruses from animals to humans, are now widely documented around the world. Scientists even consider that this is a principal mechanism for the spreading of new viruses.

But the fact that the pandemic began in the vicinity of a main virus research centre that specialises in the study of coronaviruses with epidemic potential in humans – the Wuhan Institute of Virology – has given rise to another hypothesis, the lab leak theory. Lab accidents have already led to human infections, including the H1N1 flu pandemic of 1977, which killed more than 700,000 people.

Which theory is correct? In the absence of definitive proof, and without promoting conspiracy theories, there needs to be a serious international conversation about the origin of SARS-CoV-2.

The zoonosis theory

In the scientific community, the debate on the origin of SARS-CoV-2 started with the publication of two articles at the very beginning of the outbreak.

The first, dated February 19, 2020, was published in the medical science journal The Lancet. This article, signed by 27 scientists, highlighted the efforts of Chinese experts to identify the source of the pandemic and share the results. The authors deplored “rumours and misinformation” about the origins of the virus, and stated that they “strongly condemn conspiracy theories suggesting that Covid-19 does not have a natural origin”. The authors based their opinion on the first published sequence data, but did not detail the scientific arguments supporting a natural origin.

In March 2020, another article published in Nature Medicine provided a series of scientific arguments in favour of a natural origin. The authors argued:

• The natural hypothesis is plausible, as it is the usual mechanism of emergence of coronaviruses

• The sequence of SARS-CoV-2 is too distantly related from other known coronaviruses to envisage the manufacture of a new virus from available sequences

• Its sequence does not show evidence of genetic manipulation in the laboratory.

This last argument can be questioned, as methods do exist which allow scientists to modify viral sequences without leaving a trace. These include cutting the genome into fragments that can later be joined together or, more recently, using the ISA protocol, whereby overlapping fragments naturally come together in cells through homologous recombination: a phenomenon in which two DNA molecules exchange fragments. Besides, genetic manipulation is not the only scenario compatible with a laboratory accident or leak.

Meanwhile, intense research that has been carried out for more than a year to try to prove the zoonotic scenario has not been successful so far: all 80,000 animal samples, from some 30 species, have tested negative. The samples came from farm animals and wild animals from different provinces in China. But it is important to note that this large number of negative samples does not refute the zoonotic scenario.

The lab theory

The first articles arguing for the laboratory accident theory received little attention, perhaps because they came from groups like the Bulletin of the Atomic Scientists, which tends to be critical of technology, or outsiders such as the DRASTIC team (an acronym for “decentralized radical autonomous search team investigating Covid-19”).

Composed of 24 self-styled “Twitter detectives” who are mostly anonymous with the exception of a few scientists participating under their real names, the DRASTIC group formed on Twitter in 2020 and has set itself the mission of exploring the origins of SARS-CoV-2. Information and arguments from the group have been examined in their own right, taken up and developed by some virologists, microbiologists and science communicators.

In July 2020, one of the authors of this article, Etienne Decroly, co-wrote a scientific paper discussing the possibility of a laboratory accident. The lab leak theory gained wider traction after a May 13 article in the journal Science, signed by 18 scientists, called again for the origins of SARS-CoV-2 to be examined.

So is it possible? Several elements regarding the emergence of the virus do raise questions. In particular, it has been established that the Wuhan Institute of Virology was handling viruses close to SARS-CoV-2 collected in southern China.

In addition to direct genetic manipulation, a laboratory accident could also have occurred as a result of infection during collection in the wild or during an experiment with a virus that evolved in cells or mice in the laboratory, without necessarily directly manipulating its genome.

How can we find out for sure?

In an investigation at the start of this year, a joint commission between China and the World Health Organization (WHO) failed to identify the cause of the pandemic, concluding that a zoonotic origin is most likely and the hypothesis of a laboratory accident is very unlikely. But the director-general of the WHO, Tedros Adhanom Ghebreyesus, announced there were still questions that “will need to be addressed by further studies”.

Determining whether SARS-CoV-2 has escaped from a laboratory will require a more thorough investigation in which investigators have access to sequence databases as well as to the various resources used by Chinese researchers, including laboratory notebooks, submitted projects, scientific manuscripts, viral sequences, order lists and biological analyses. Unfortunately, sequence databases for SARS-CoV-2 have been inaccessible to scientists since September 2019.

In the absence of direct evidence, alternative approaches may provide additional information. By analysing the available sequences of SARS-CoV-2-like coronaviruses in detail, it is possible that the scientific community will reach a consensus based on strong clues, as they did for other outbreaks, including the 1977 H1N1 virus.

Biological black boxes

Whether the origin is zoonotic or not, it is necessary to question the consequences of our interactions with ecosystems, the industrialisation of intensive breeding, safety protocols on collecting and experimenting on potentially pandemic viruses, and the proliferation of high-security laboratories, particularly those near megacities.

We need to equip facilities that study viruses with safety systems as demanding as those used for studying nuclear energy. This could include the introduction of “biological black boxes”, similar to flight recorders which allow investigators to recreate the final moments of a plane accident. Access to certain high-risk labs could be made dependent on detailed digital descriptions of experiments; sequencing data could be systematically archived; laboratory air filters could be collected, and if there is a suspicion of pathogen dissemination, the genetic material on their surface could be sequenced.

Such new safety measures should be put in place internationally to limit the risk of future pandemics. As for SARS-CoV-2, it is important to trace its exact origins in order to understand precisely what flaws may have led to its spread.

Virginie Courtier, Directrice de recherche CNRS, génétique et évolution, Université de Paris and Etienne Decroly, Directeur de recherche en virologie, Aix-Marseille Université (AMU)

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Will the end of the COVID-19 pandemic usher in a second Roaring ’20s?

While some places remain mired in the third wave of the pandemic, others are taking their first tentative steps towards normality. Since April 21, Denmark has allowed indoor service at restaurants and cafes, and football fans are returning to the stands. In countries that have forged ahead with the rollout of vaccines, there is a palpable sense of optimism.

And yet, with all this looking forward, there is plenty of uncertainty over what the future holds. Articles on what the world will look like post-pandemic have proliferated and nations worldwide are considering how to recover financially from this year-long economic disaster.

Almost exactly a hundred years ago, similar conversations and preparations were taking place. In 1918, an influenza pandemic swept the globe. It infected an estimated 500 million people — around a third of the world’s population at the time — in four successive waves. While the end of that pandemic was protracted and uneven, it was eventually followed by a period of dramatic social and economic change.

The Roaring ‘20s — or “années folles” (“crazy years”) in France — was a period of economic prosperity, cultural flourishing and social change in North America and Europe. The decade witnessed a rapid acceleration in the development and use of cars, planes, telephones and films. In many democratic nations, some women won the right to vote and their ability to participate in the public sphere and labour market expanded.

Parallels and differences

As a historian of health care, I see some striking similarities between then and now, and as we enter our very own '20s it is tempting to use this history as a way of predicting the future.

Vaccine rollouts have raised hope for an end to the COVID-19 pandemic. But they’ve also raised questions about how the world might bounce back, and whether this tragic period could be the start of something new and exciting. Much like in the 1920s, this disease could prompt us to reconsider how we work, run governments and have fun.

However, there are some crucial differences between the two pandemics that could alter the trajectory of the upcoming decade. For one, the age-profile of the victims of the influenza pandemic was unlike that of COVID-19.

The 1918 flu — also called the Spanish flu — predominantly affected the young, whereas COVID-19 has mostly killed older people. As a result, fear probably refracted through the two societies in different ways.

Young people have certainly been affected by the COVID-19 pandemic: the virus has posed a threat to those with underlying health conditions or disabilities of all ages, and some of the variants have been more likely to affect younger people. A year of lockdowns and shelter-in-place orders has had a damaging effect on mental and emotional health, and young people have experienced increased anxiety.

Read more: COVID-19’s parallel pandemic: Why we need a mental health 'vaccine'

However, the relief of surviving the COVID-19 pandemic might not feel quite the same as that experienced by those who made it through the 1918 influenza pandemic, which posed an immediate risk of death to those in their 20s and 30s.

1918 vs. 2020

Crucially, the 1918 flu came immediately after the First World War, which produced its own radical reconstitution of the social order. Despite the drama and tragedy of 2020, the changes we are living through now might be insufficient to produce the kind of social transformation witnessed in the 1920s. One of the key features of the Roaring '20s was an upending of traditional values, a shift in gender dynamics and the flourishing of gay culture.

While the prospect of similar things happening in the 2020s might seem promising, the pandemic has reinforced, rather than challenged, traditional gender roles. There is evidence for this all over the world, but in the United States research suggests that the risk of mothers leaving the labour force to take up caring responsibilities at home amounts to around US$64.5 billion per year in lost wages and economic activity.

When most people think of the Roaring '20s they probably call to mind images of nightclubs, jazz performers and flappers — people having fun. But fun costs money. No doubt, there will be plenty of celebration and relief when things return to a version of normality, but hedonism will probably be out of reach for most.

Young people in particular have been hard hit by the financial pressures of COVID-19. Workers aged 16-24 face high unemployment and an uncertain future. While some have managed to weather the economic storm of this past year, the gap between rich and poor has widened.

Inequality and isolationism

Of course, the 1920s was not a period of unadulterated joy for everyone. Economic inequality was a problem then just as it is now. And while society became more liberal in some ways, governments also enacted harsher and more punitive policies, particularly when it came to immigration — specifically from Asian countries.

The Immigration Act of 1924 limited immigration to the U.S. and targeted Asians. Australia and New Zealand also restricted or ended Asian immigration and in Canada, the Chinese Immigration Act of 1923 imposed similar limitations.

There are troubling signs that this might be the main point of similarity between then and now. Anti-Asian sentiment has increased and many countries are using COVID-19 as a way of justifying harsh border restrictions and isolationist policies.

In our optimism for the future, we must remain alert to all the different kinds of damage the pandemic could cause. Just as disease can be a mechanism for positive social change, it can also entrench inequalities and further divide nations and communities.

Agnes Arnold-Forster, Researcher, History of Medicine and Healthcare, McGill University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Will the COVID vaccine make me test positive for the coronavirus? 5 questions about vaccines and COVID testing answered

COVID-19 vaccination is rolling out across Australia. So health authorities are keen to dispel myths about the vaccines, including any impact on COVID testing.

Do the vaccines give you COVID, or make you test positive for COVID? Does the vaccine affect other tests? Do we still need to get COVID tested if we have symptoms, even after getting the shot? And will we still need COVID testing once more of the population gets vaccinated?

We look at the evidence to answer five common questions about the impact of COVID vaccines on testing.

Read more: Do I need to register for a COVID vaccine? How will I know when it's my turn? Vaccine rollout questions answered

1. Will the vaccine give me COVID?

The short answer is “no”. That’s because the vaccines approved for use so far in Australia and elsewhere don’t contain live COVID virus.

The Pfizer/BioNTech vaccine contains an artificially generated portion of viral mRNA (messenger ribonucleic acid). This carries the specific genetic instructions for your body to make the coronavirus’s “spike protein”, against which your body mounts a protective immune response.

The AstraZeneca vaccine uses a different technology. It packages viral DNA into a viral vector “carrier” based on a chimpanzee adenovirus. When this is delivered into your arm, the DNA prompts your body to produce the spike protein, again stimulating an immune response.

Any vaccine side-effects, such as fever or feeling fatigued, are usually mild and temporary. These are signs the vaccines are working to boost your immune system, rather than signs of COVID itself. These symptoms are also common after routine vaccines.

2. Will the COVID vaccine make me test positive?

No, a COVID vaccine will not affect the results of a diagnostic COVID test.

The current gold-standard diagnostic test is known as nucleic acid PCR testing. This looks for the mRNA (genetic material) of SARS-CoV-2, the virus that causes COVID-19. This is a marker of current infection.

This is the test the vast majority of people have when they line up at a drive-through testing clinic, or attend a COVID clinic at their local hospital.

Yes, the Pfizer vaccine contains mRNA. But the mRNA it uses is only a small part of the entire viral RNA. It also cannot make copies of itself, which would be needed for it to be in sufficient quantity to be detected. So it cannot be detected by a PCR test.

The AstraZeneca vaccine also only contains part of the DNA but is inserted in an adenovirus carrier that cannot replicate so cannot give you infection or a positive PCR test.

Read more: How mRNA vaccines from Pfizer and Moderna work, why they're a breakthrough and why they need to be kept so cold

3. How about antibody testing?

While PCR testing is used to look for current infection, antibody testing — also known as serology testing — picks up past infections.

Laboratories look to see if your immune system has raised antibodies against the coronavirus, a sign your body has been exposed to it. As it takes time for antibodies to develop, testing positive with an antibody test may indicate you were infected weeks or months ago.

But your body also produces antibodies as a response to vaccination. That’s the way it can recognise SARS-CoV-2, the next time it meets it, to protect you from severe COVID.

So as COVID vaccines are rolled out, and people develop a vaccine-induced antibody response, it may become difficult to differentiate between someone who has had COVID in the past and someone who was vaccinated a month ago. But this will depend on the serology test used.

Read more: Antibody tests: to get a grip on coronavirus, we need to know who's already had it

The good news is that antibody testing is not nearly as common as PCR testing. And it’s only ordered under limited and rare circumstances.

For instance, when someone tests positive with PCR, but they are a false positive due to the characteristics of the test, or have fragments of virus lingering in the respiratory tract from an old infection, public health experts might request an antibody test to see whether that person was infected in the past. They might also order an antibody test during contact tracing of cases with an unknown source of infection.

Read more: Why can't we use antibody tests for diagnosing COVID-19 yet?

4. If I get vaccinated, do I still need a COVID test if I have symptoms?

Yes, we will continue to test for COVID as long as the virus is circulating anywhere in the world.

Even though the COVID vaccines are looking promising in preventing people from getting seriously sick or dying, they won’t provide 100% protection.

Real-world data suggests some vaccinated people can still catch the virus, but they usually only get mild disease. We are unsure whether vaccinated people will be able to potentially pass it to others, even if they don’t have any symptoms. So it’s important people continue to get tested.

Furthermore, not everyone will be eligible to receive a COVID-19 vaccine. For instance, in Australia, current guidelines exclude people under 16 years of age, and those who are allergic to ingredients in the vaccine. And although pregnant women are not ruled out from receiving the vaccine, it is not routinely recommended. This means a proportion of the population will remain susceptible to catching the virus.

We also are unsure about how effective vaccines will be against emerging SARS-CoV-2 variants. So we will continue to test to ensure people are not infected with these strains.

Read more: UK, South African, Brazilian: a virologist explains each COVID variant and what they mean for the pandemic

We know testing, detecting new cases early and contact tracing are the core components of the public health response to COVID, and will continue to be a priority from a public health perspective.

Minimum numbers of daily COVID tests are also needed so we can be confident the virus is not circulating in the community. As an example, New South Wales aims for 8,000 or more tests a day to maintain this peace of mind.

Continued vigilance and high rates of testing for COVID will also be important as we enter the flu season. That’s because the only way to differentiate between COVID and influenza (or any other respiratory infection) is via testing.

5. Will testing for COVID stop as time goes on?

It is unlikely our approach to COVID testing will change in the immediate future. However, as COVID vaccines are rolled out and since COVID is likely to become endemic and stay with us for a long time, the acute response phase to the pandemic will end.

So COVID testing may become part of managing other infectious diseases and part of how we respond to other ongoing health priorities.

Read more: Coronavirus might become endemic – here's how

Meru Sheel, Epidemiologist | Senior Research Fellow, Australian National University; Charlee J Law, Epidemiologist | Research Associate, Australian National University, and Cyra Patel, PhD candidate, Australian National University

This article is republished from The Conversation under a Creative Commons license. Read the original article.