Italian blood samples revive debate over first signs of Covid in Europe

Renewed tests of blood samples collected in Italy as early as October 2019 have revived a debate over whether coronavirus was circulating in Europe before Chinese authorities confirmed the first case in Wuhan.

Scientists from Milan’s Istituto Nazionale Tumori, a cancer research centre, wrote in a new paper, published on Monday, that retesting of a small number of pre-pandemic blood samples by two laboratories had indicated the presence of antibodies normally observed after coronavirus infections.

“The results of this retesting suggest that what we previously reported in asymptomatic patients is a plausible signal of early circulation of the virus in Italy,” Giovanni Apolone, one of the researchers, told the Financial Times.

“If this is confirmed, this would explain the explosion of symptomatic cases observed in Italy [in 2020]. Sars-Cov-2, or an earlier version, circulated silently, under the surface,” he said.

The Italian researchers originally screened 959 individuals for lung cancer before the pandemic. Last year they tested the samples again, looking for coronavirus-linked antibodies, and said they had found traces of infection.

At the request of the World Health Organization those samples were retested by the VisMederi laboratory in Siena, Italy and a WHO-affiliated facility at Erasmus University in the Netherlands.

Marion Koopmans, head of virology at Erasmus, said the new results were “interesting”. However, she cautioned that while there was some evidence of antibodies, none of the samples provided conclusive proof of prior infection with Covid-19, based on the university’s strict criteria.

“We use a rather stringent threshold and cannot rule out that some of the observed reactivity is real,” she said. “However, for confirmation of earlier circulation we would recommend studies of patients with unexplained illness for virological confirmation.”

The laboratories retested 29 of the original Italian samples, some positive and some negative, along with 29 control cases from 2018.

From these tests, three samples were found by both Erasmus and VisMederi to be positive for a type of coronavirus-linked antibody, IgM, that typically indicates recent infection. The earliest was collected on October 10 2019. One of the samples, from February 5 2020, was also positive for so-called neutralising antibodies.

However, none of the samples contained high enough levels of each of the three types of antibodies that Erasmus requires to be considered proof of infection — IgM, neutralising antibodies and a third antibody known as IgG.

In another nine samples that VisMederi said were positive for infection, levels of IgM antibodies were below the cut off point set by Erasmus, Gabriella Sozzi, one of the Italian researchers said.

Sozzi argued that in the pre-pandemic period, the virus may have been less aggressive or contagious, which made it “necessary to use highly sensitive tests despite the risk of finding ‘false positive’ cases”.

Koopmans said that Erasmus university’s stringent criteria were necessary to conclusively state whether the pandemic started earlier than currently thought. “That does not mean it is impossible,” she said. “Just that you would like to see other pieces of evidence.”

The Italian paper, which has not been peer-reviewed, did not address the question of where the novel coronavirus originated, but the findings are likely to stoke the debate over whether Covid-19 was circulating in Italy or elsewhere before the first confirmed case in Wuhan in December 2019. Other studies have placed the first cases in Europe as early as November 2019, including one in Milan.

The WHO said it was not part of the laboratory analysis and that the results highlighted the challenge of conducting antibody tests on samples from 2019. It said it was “grateful” to scientists trying to advance the understanding of the origins of Covid-19.

Additional reporting by Yuan Yang in Beijing and Clive Cookson in London

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