The University of Barcelona today announced the results of a study that could change history We know so far about SARS-CoV-2, the coronavirus causing the greatest pandemic in over a hundred years.
Of according to the ‘preprint’ (article not subject to external review) posted in the medRxiv repository on June 13 – and of which surprisingly there had been no news in these last two weeks – viral RNA would have already been detected in the wastewater of the city of Barcelona in March 2019, that is, nine months before China declared its outbreak in Wuhan.
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The researchers – from the UB, Aigües de Barcelona and the CSIC – led by the virologists Albert Bosch and Rosa Pintó, give good results: “All samples were found to be negative for the presence of SARS-CoV-2 genomes with the exception of March 12, 2019, in which the objective tests for IP2 and IP4 were positive.”
IP2 and IP4 are two essential enzymes for virus replication. “This surprising finding indicates that there was circulation of the virus in Barcelona long before any case of covid-19 in the world was reported,” they added in the study. “Barcelona is a center for business and commerce, as well as a popular venue for mass events, bringing together visitors from many parts of the world. It is however similar situations likely to have occurred in other parts of the world, with the circulation of unnoticed cases of covid-19 in the community. “
There was circulation of the virus in Barcelona long before any case of covid-19 in the world was reported
First, it is true that sewage analysis is proving to be an excellent sentinel for predicting outbreaks. Partly because between 16% and 73% of those infected declares having diarrhea as one of the symptoms. Thanks to them, it was detected that the coronavirus was circulating in Spain before even registering the first known cases in late January.
However, the results are so surprising and unprecedented in any other part of the world that force you to be a little skeptical. What could have happened?
First we have the evidence for the genetics of the virus. The presence of SARS-CoV-2 was first detected in December 2019 in China, But how long had it been circulating?
An analysis carried out at University College London of the mutations that the coronavirus has suffered throughout these months, in which the pathogen was sequenced to 7,500 people around the world, limited the appearance of SARS-CoV-2 at the end of the last year: “Phylogenetic estimates support that the covid-19 pandemic started sometime Between October 6, 2019 and December 11, 2019, which corresponds to the moment of the jump from the host to the humans “, explained François Balloux, one of the researchers involved in the work, who published in the magazine ‘Infection, Genetics and Evolution’.
On the other hand, there is the particularity of the technique used. The epidemiology of wastewater consists of taking samples of this liquid, amplifying its components using a PCR technique and locating traces of drugs or viruses. Due to its low invasiveness, it is very promising but it is still a premature branch of knowledge to draw too many conclusions, particularly when the amounts are almost undetectable.
The technique used
Researchers from the University of Valencia and the CSIC who have participated in the Barcelona study previously carried out a similar study with wastewater from the city of Turia where they detected the first evidence that the virus was circulating in Valencia on February 24. In this work However, they admit that “compared to the systematic testing of individuals, wastewater analysis is obviously less invasive, simpler and cheaper, but the sensitivity and reliability of this method remains to be seen.”
The sensitivity and reliability of wastewater analysis remains to be seen.
The other important element is the amount detected. Many previous works have been done with other types of microorganisms such as norovirus, which are the ones that normally cause gastroenteritis, and although detection with SARS-CoV-2 seems even more sensitive, Dutch pioneers of this technique estimate that the first positives “were observed with three of the first four sets when the reported cases of Covid-19 they reached between five and ten cases for every one hundred thousand inhabitants“.
With this sensitivity, in Barcelona (3.3 million inhabitants in its metropolitan area) there should have been between 162 and 324 cases of covid-19 in March 2019 so that it would have been detectable by these forensic scientists.
No trace of genes N1 to N3
Another important detail is that Gertjan Medema and his colleagues at the Dutch KWR Water Research Institute were specifically looking for N1, N2, N3 and E gene nucleotide fragments to identify the SARS-CoV-2 virus. Virologists from the University of Barcelona also, although curiously in the samples of March 12 only the aforementioned IP2 and IP4 were detected. As for the N1, N2, N3 and E nothing detectable appeared In the analysis.
Other studies in Australia or Boston have done a similar analysis also adding other genes. The problem with such a new discipline is that it is unclear what specific part of the virus to look for or detect to proclaim that SARS-CoV-2 is circulating through the wastewater of a city. Almost all the studies published so far seem to agree that the detection of fragments from N1 to N3 is important, which is just what was not detected in Barcelona.
In short, everyone is trying to cross data to discover how to validate the results obtained in this promising field of research in wastewater epidemiology. Many researchers warn that many errors are appearing due to ‘subsampling’ (the sample is too small) or false positives. Yes, there seems to be a consensus that the ‘target genes’, those genes that should be the target of the search, are N1 and N2 as explains this other study conducted in Ecuador. Those genes do not appear in the Barcelona work until
If it were a PCR by blood tests it would be irreversible, but the wastewater still leaves many doubts, since even a downpour is capable of affecting the detectable levels of the virus.
Has this been the case in Barcelona? It has been the university hastened to sell the skin of the ‘preprint’ before screwing it on? The Confidential has contacted the authors of the Barcelona paper to assess these issues, with no response at the time of publication of this article. We will continue to report.