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expert reaction to perspective looking at the early cases of COVID-19 in Wuhan

A perspective piece published in Science investigates the origin of the COVID-19 pandemic.


Prof James Wood, Head of Department of Veterinary Medicine, University of Cambridge, said:

“The investigation of the origins of the pandemic remains important, not least as we aim to learn about future pandemic prevention. The thorough investigation by Dr Worobey represents a clear advance in documenting early, clinically evident cases of COVID-19. There is a new WHO group also tasked with investigating the origins. It is important to recognise however that retrospective investigation after such a time gap is inevitably challenging and also that, for a disease that has at least 40% inapparent, or asymptomatic infection, and a large proportion of mild infections that are additionally very mild and indistinguishable from other respiratory infections, it is at best optimistic to think that we will ever track the patient zero. For example, other research, by Emma Glennon, has demonstrated that we fail to diagnose over 50% of Ebola index cases that have caught the infection from animals, even in known high risk areas. It is highly likely that we will never find a smoking gun for COVI-19 and will only be able to make statements that reflect the balance of probabilities for the pandemic source.”


Prof David Robertson, MRC Investigator, Head of CVR Bioinformatics MRC-University of Glasgow Centre for Virus Research (CVR), said:

“The careful analysis by Michael Worobey based on personal accounts of the early COVID cases from hospital staff and patients confirms categorically that the Huanan Seafood Market was the significant epicentre for the spillover of SARS-CoV-2. There had been a question around this because not all of the cases had a clear link to the market but Worobey shows many of these lived close by. This suggests there wasn’t extensive community transmission outside of this immediate area. We also now know how frequently mild cases are so it’s not surprising not all of the early cases are clearly linked to the Huanan market as many of these will be have been human to human transmission that were not detected. 

“On the side of there being a lab-leak from the Wuhan Institute of Virology it’s some distance from the location of the Huanan market which supports, as we always suspected, WIV happening to be in Wuhan is a coincidence. Collectively the data (early case reports, epidemiological, genomics, serology & evolutionary information) all point firmly to a SARS-like spillover associated with the selling of live animals in markets (”


Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:

“I know of some of Worobey’s work – the author who write this Sciences article – particularly in discerning the origins of HIV:

“What he does – like other evolutionary biologists and phylogeneticists – is to apply complex evolutionary models to older, dated viral sequences to infer the dates of origins of these viruses into human populations from animal reservoirs.

“For this to work accurately, both the model and the dated sequence (obtained from old, stored infected blood or tissue samples) have to be robust and comprehensive,

“i.e. the model of evolution has to be truly representative of how a particular virus evolves in the human population, and there needs to be sufficient dated viral sequences going far back enough in time to infer the origins of that virus into that human population.

“This is like drawing your own family tree – you may know when and where you, your parents, and even your grandparents were born and died – but what about your great, great, great grand parents? How do you look for this information? Family documents, city/town/village archives on births, deaths, marriages (due to name changes), etc. Then you gradually piece together your family tree – when and where they were born, how many siblings – their names, dates of birth, where they lived and died, etc.

“Worobey does the same with viruses – he finds as many viral sequences with collection dates as he can from old samples, then he draws a virus family tree going back in time as far as he can to the very first human case of the virus in that population.

“Then further back in the past – when there are no more reported human cases, he has to then look for similar animal viruses – like those in bats or the pangolin for SARS-COV-2 – to see where the virus came from, e.g. like birds for influenza, monkeys for HIV, bats for coronavirus, Nipah virus, Ebola, etc.

“All he is saying in this Science article is that we need better, more comprehensive patient case and dated viral sequence data – at the time of first appearance of these viruses – to make this viral phylogenetic/evolutionary history approach more accurate – so that we can then determine where this pandemic originated so we can monitor and prevent a similar pandemic arising again.

“In the article, he reports on the earlier human cases of COVID-19 which would have been infected with earlier viruses in the evolutionary tree – but which were not  sampled/sequenced – we are missing out on data that would give us a more accurate picture of how this virus entered the human population – which might help us prevent the next pandemic.

“But he is not a doctor so he is unfamiliar with the clinical process which is generally quite messy.

“Patients present to hospital with pneumonia are very common and the admitting team may take a swab for diagnosis at that time – which gets tested in the lab – then often discarded with no sequencing – unless there is an active surveillance system is in place to keep all pneumonia case samples for further sequencing – but if we did this, hospital labs will need extra funding for more freezers to store all the positive samples, as well as funding to sequence them all – ideally, in real-time on a continuous basis – and most pneumonia cases will not be anything unusual.

“So whilst Worobey is asking for an ideal, real-time, contemporaneous data collection approach to such pneumonia cases – it will take some time before clinical/public health teams realise that they are dealing with something unusual – by which time the earlier samples may have been discarded (usually via autoclaving or incineration).

“I am both a clinical doctor/virologist and a PhD scientist – so I understand what he is saying/asking – but I also run hospital diagnostic Virology lab – so I know that the practical and funding constraints are significant, unless they are part of a long-term dedicated surveillance programme – which may well be needed after this COVID-19 pandemic – otherwise, we cannot keep all samples for all patients forever – we just don’t have the space and -80 C freezers are very expensive to buy and run.”



All our previous output on this subject can be seen at this weblink:



Dissecting the early COVID-19 cases in Wuhan’ by Michael Worobey was published in Science on November 18, 2021.



Declared interests

None received.

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