Dominic Dwyer, University of SydneySARS-CoV-2 has caused the greatest pandemic of the past 100 years. Understanding its origins is crucial for knowing what happened in late 2019 and for preparing for the next pandemic virus.
These studies take time, planning and cooperation. They must be driven by science — not politics or posturing. The investigation into the origins of SARS-CoV-2 has already taken too long. It has been more than 20 months since the first cases were recognised in Wuhan, China, in December 2019.
This week US President Joe Biden was briefed by United States intelligence agencies on their investigation into the origins of the virus responsible for COVID-19, according to media. Parts of the investigation’s report are expected to be publicly released within the next few days.
An early report from the New York Times suggests the investigation does not conclude whether the spread of the virus resulted from a lab leak, or if it emerged naturally in a spillover from animals to humans.
While a possible lab leak is a line of inquiry (should scientific evidence emerge), it musn’t distract from where the current evidence tells us we should be directing most of our energy. The more time that passes, the less feasible it will become for experts to determine the biological origins of the virus.
I was one of the experts who visited Wuhan earlier this year as part of the World Health Organisation’s investigation into SARS-CoV-2 origins. We found the evidence pointed to the pandemic starting as a result of zoonotic transmission of the virus, meaning a spillover from an animal to humans.
Our inquiry culminated in a report published in March which made a series of recommendations for further work. There is an urgent need to get on with designing studies to support these recommendations.
Today, myself and other independent authors of the WHO report have written to plead for this work to be accelerated. Crucial time is disappearing to work through the six priority areas, which include:
- further trace-back studies based on early disease reports
- SARS-CoV-2-specific antibody surveys in regions with early COVID-19 cases. This is important given a number of countries including Italy, France, Spain and the United Kingdom have often reported inconclusive evidence of early COVID-19 detection
- trace-back and community surveys of the people involved with the wildlife farms that supplied animals to Wuhan markets
- risk-targeted surveys of possible animal hosts. This could be either the primary host (such as bats), or secondary hosts or amplifiers
- detailed risk-factor analyses of pockets of early cases, wherever these have occurred
- and follow up of any credible new leads.
Race against the clock
The biological feasibility of some of these studies is time dependent. SARS-CoV-2 antibodies emerge a week or so after someone has become infected and recovered from the virus, or after being vaccinated.
But we know antibodies decrease over time — so samples collected now from people infected before or around December 2019 may be harder to examine accurately.
Using antibody studies to differentiate between vaccination, natural infection, or even second infection (especially if the initial infection occurred in 2019) in the general population is also problematic.
For example, after natural infection a range of SARS-CoV-2-specific antibodies, such as to the spike protein or nucleoprotein, can be detected for varying lengths of time and in varying concentrations and ability to neutralise the virus.
But depending on the vaccine used, antibodies to the SARS-CoV-2 spike protein may be all that is detected. These, too, drop with time.
There is also a need to have international consensus in the laboratory methods used to detect SARS-CoV-2-specific antibodies. Inconsistency in testing methods has led to arguments about data quality from many locations.
It takes time to come to agreement on laboratory techniques for serological and viral genomic studies, sample access and sharing (including addressing consent and privacy concerns). Securing funding also takes time — so time is not a resource we can waste.
Distance from potential sources
Moreover, many wildlife farms in Wuhan have closed down following the initial outbreak, generally in an unverified manner. And finding human or animal evidence of early coronavirus spillover is increasingly difficult as animals and humans disperse.
Fortunately, some studies can be done now. This includes reviews of early case studies, and blood donor studies in Wuhan and other cities in China (and anywhere else where there was early detection of viral genomes).
It is important to examine the progress or results of such studies by local and international experts, yet the mechanisms for such scientific cross-examination have not yet been put in place.
New evidence has come forward since our March report. These papers and the WHO report data have been reviewed by scientists independent of the WHO group. They have came to similar conclusions to the WHO report, identifying:
- the host reservoir for SARS-CoV-2 has not been found
- the key species in China (or elsewhere) may not have been tested
- and there is substantial scientific evidence supporting a zoonotic origin.
Teetering back and forth
While the possibility of a laboratory accident can’t be entirely dismissed, it is highly unlikely, given the repeated human-animal contact that occurs routinely in the wildlife trade.
Still, the “lab-leak” hypotheses continue to generate media interest over and above the available evidence. These more political discussions further slow the cooperation and agreement needed to progress with the WHO report’s phase two studies.
The World Health Organisation has called for a new committee to oversee future origins studies. This is laudable, but there is the risk of further delaying the necessary planning for the already outlined SARS-CoV-2 origins studies.
Michael Toole, Burnet InstituteUrgent global action is needed to end the COVID-19 pandemic and prepare for future threats, according to a new report by the Independent Panel for Pandemic Preparedness and Response.
The panel, co-chaired by former New Zealand prime minister Helen Clark and former Liberian president Ellen Johnson Sirleaf, criticises the World Health Organization (WHO) for its tardy actions during the first months of 2020.
The WHO was slow to warn of person-to-person transmission after it first received this information in Wuhan, China, in early January.
And it was slow to declare a public health emergency of international concern (PHEIC), which it did on January 30.
The WHO also opposed international travel restrictions that, if implemented earlier, might have slowed the international spread of the virus. By the time the PHEIC was declared, COVID-19 had spread to 18 countries outside China.
But WHO’s hands were tied
While this may appear just a scathing criticism of the world’s peak health body, the WHO had its hands tied by the international framework that governs the response to emerging infectious diseases and pandemics, the International Health Regulations (IHR).
The regulations imposed new requirements that must be met before the WHO director general could act on emergencies, rather than enabling the WHO to act immediately and independently.
The regulations also prohibit international travel restrictions in public health emergencies.
Many member nations failed to act
The report describes February 2020 as a “lost month”, referring to the time between the declaration of a PHEIC and the WHO statement on March 11 that characterised COVID-19 as a pandemic.
The panel found this was due to a lack of understanding that the PHEIC declaration was the loudest possible alarm open to the director general. The pandemic declaration was not based on International Health Regulation guidelines.
The panel found a number of countries took a wait-and-see attitude during February 2020, allowing the virus to spread uncontrollably.
Effective and high-level coordinating bodies were critical to a country’s ability to adapt to changing information. Yet only a few countries set in motion comprehensive and coordinated COVID-19 protection and response measures.
Of the 28 country responses the panel analysed in depth, only a handful adopted aggressive containment strategies, including China, New Zealand, South Korea, Singapore, Thailand and Vietnam.
Some others had uncoordinated approaches that devalued science, denied the potential impact of the pandemic, delayed comprehensive action and allowed distrust to undermine efforts. While not named, the United States and Brazil were probably among them.
The report praises the role of the African Union and the Africa CDC in leading a continent-wide coordinated response.
It also singles out research and development as a major achievement, especially in vaccine development.
Preparation was inadequate
Despite the lessons learned from previous outbreaks of SARS, H1N1 (avian flu), Zika, MERS (Middle East respiratory syndrome) and Ebola, preparedness was vastly underfunded.
The US government, led by the Centres for Disease Control, established the Global Health Security Agenda, a group of 70 countries — including Australia – committed to building global capabilities to implement the International Health Regulations. But the Trump administration defunded most of the US CDC’s activities under the agenda.
After the H1N1 pandemic, Australia reviewed its health sector response and made many recommendations for future preparedness. However, inaction followed. Australia has not run a large-scale pandemic simulation exercise since 2008.
Australia also dropped the ball on regional pandemic preparedness. After the SARS outbreak in 2003, the government developed a five-year regional emerging diseases and pandemics strategy, which received A$100 million from the Howard government. Yet the second five-year strategy attracted very little funding.
Fixing the global system
The panel urges immediate action to end the pandemic through:
- accelerated vaccination
- proven measures such as masks and social distancing
- testing and contact tracing.
However, the focus of its recommendations is on future preparedness.
The panel is convinced a Global Health Threats Council at the most senior level is vital to future success. It would help secure high-level political leadership and ensure attention to pandemic prevention, preparedness and response is sustained over time. Such a body is long overdue.
To ensure the WHO is more agile, the panel recommends an increase in the proportion of funding that is unearmarked for specific programs and countries. This would allow for financial reserves to respond to sudden, unexpected events. It also needs an improved surveillance system, quicker alerts for emerging virus threats, and authority to publish information and dispatch expert missions immediately.
Transparency, speed, flexibility to act more independently and better resourcing are critical to the reforms proposed. Efforts to do this will need unqualified support from its member nations, starting at this month’s World Health Assembly.
After the disruptive years of the Trump presidency, the WHO needs restoration. Australia is influential and should be at the forefront of ensuring this happens.
As I write, I am in hotel quarantine in Sydney, after returning from Wuhan, China. There, I was the Australian representative on the international World Health Organization’s (WHO) investigation into the origins of the SARS-CoV-2 virus.
As part of the mission, we met the man who, on December 8, 2019, was the first confirmed COVID-19 case; he’s since recovered. We met the husband of a doctor who died of COVID-19 and left behind a young child. We met the doctors who worked in the Wuhan hospitals treating those early COVID-19 cases, and learned what happened to them and their colleagues. We witnessed the impact of COVID-19 on many individuals and communities, affected so early in the pandemic, when we didn’t know much about the virus, how it spreads, how to treat COVID-19, or its impacts.
We talked to our Chinese counterparts — scientists, epidemiologists, doctors — over the four weeks the WHO mission was in China. We were in meetings with them for up to 15 hours a day, so we became colleagues, even friends. This allowed us to build respect and trust in a way you couldn’t necessarily do via Zoom or email.
This is what we learned about the origins of SARS-CoV-2.
Animal origins, but not necessarily at the Wuhan markets
It was in Wuhan, in central China, that the virus, now called SARS-CoV-2, emerged in December 2019, unleashing the greatest infectious disease outbreak since the 1918-19 influenza pandemic.
Our investigations concluded the virus was most likely of animal origin. It probably crossed over to humans from bats, via an as-yet-unknown intermediary animal, at an unknown location. Such “zoonotic” diseases have triggered pandemics before. But we are still working to confirm the exact chain of events that led to the current pandemic. Sampling of bats in Hubei province and wildlife across China has revealed no SARS-CoV-2 to date.
We visited the now-closed Wuhan wet market which, in the early days of the pandemic, was blamed as the source of the virus. Some stalls at the market sold “domesticated” wildlife products. These are animals raised for food, such as bamboo rats, civets and ferret badgers. There is also evidence some domesticated wildlife may be susceptible to SARS-CoV-2. However, none of the animal products sampled after the market’s closure tested positive for SARS-CoV-2.
We also know not all of those first 174 early COVID-19 cases visited the market, including the man who was diagnosed in December 2019 with the earliest onset date.
However, when we visited the closed market, it’s easy to see how an infection might have spread there. When it was open, there would have been around 10,000 people visiting a day, in close proximity, with poor ventilation and drainage.
There’s also genetic evidence generated during the mission for a transmission cluster there. Viral sequences from several of the market cases were identical, suggesting a transmission cluster. However, there was some diversity in other viral sequences, implying other unknown or unsampled chains of transmission.
A summary of modelling studies of the time to the most recent common ancestor of SARS-CoV-2 sequences estimated the start of the pandemic between mid-November and early December. There are also publications suggesting SARS-CoV-2 circulation in various countries earlier than the first case in Wuhan, although these require confirmation.
The market in Wuhan, in the end, was more of an amplifying event rather than necessarily a true ground zero. So we need to look elsewhere for the viral origins.
Frozen or refrigerated food not ruled out in the spread
Then there was the “cold chain” hypothesis. This is the idea the virus might have originated from elsewhere via the farming, catching, processing, transporting, refrigeration or freezing of food. Was that food ice cream, fish, wildlife meat? We don’t know. It’s unproven that this triggered the origin of the virus itself. But to what extent did it contribute to its spread? Again, we don’t know.
Several “cold chain” products present in the Wuhan market were not tested for the virus. Environmental sampling in the market showed viral surface contamination. This may indicate the introduction of SARS-CoV-2 through infected people, or contaminated animal products and “cold chain” products. Investigation of “cold chain” products and virus survival at low temperatures is still underway.
Could frozen food transmit COVID-19?
Extremely unlikely the virus escaped from a lab
The most politically sensitive option we looked at was the virus escaping from a laboratory. We concluded this was extremely unlikely.
We visited the Wuhan Institute of Virology, which is an impressive research facility, and looks to be run well, with due regard to staff health.
We spoke to the scientists there. We heard that scientists’ blood samples, which are routinely taken and stored, were tested for signs they had been infected. No evidence of antibodies to the coronavirus was found. We looked at their biosecurity audits. No evidence.
We looked at the closest virus to SARS-CoV-2 they were working on — the virus RaTG13 — which had been detected in caves in southern China where some miners had died seven years previously.
But all the scientists had was a genetic sequence for this virus. They hadn’t managed to grow it in culture. While viruses certainly do escape from laboratories, this is rare. So, we concluded it was extremely unlikely this had happened in Wuhan.
A team of investigators
When I say “we”, the mission was a joint exercise between the WHO and the Chinese health commission. In all, there were 17 Chinese and ten international experts, plus seven other experts and support staff from various agencies. We looked at the clinical epidemiology (how COVID-19 spread among people), the molecular epidemiology (the genetic makeup of the virus and its spread), and the role of animals and the environment.
The clinical epidemiology group alone looked at China’s records of 76,000 episodes from more than 200 institutions of anything that could have resembled COVID-19 — such as influenza-like illnesses, pneumonia and other respiratory illnesses. They found no clear evidence of substantial circulation of COVID-19 in Wuhan during the latter part of 2019 before the first case.
Where to now?
Our mission to China was only phase one. We are due to publish our official report in the coming weeks. Investigators will also look further afield for data, to investigate evidence the virus was circulating in Europe, for instance, earlier in 2019. Investigators will continue to test wildlife and other animals in the region for signs of the virus. And we’ll continue to learn from our experiences to improve how we investigate the next pandemic.
Irrespective of the origins of the virus, individual people with the disease are at the beginning of the epidemiology data points, sequences and numbers. The long-term physical and psychological effects — the tragedy and anxiety — will be felt in Wuhan, and elsewhere, for decades to come.