Hunt for Italy’s coronavirus patient zero finds a case in November 2019
- Peer-reviewed research shows the virus was present in a stored skin sample taken from a Milan woman with a mysterious illness
- Doctors remembered her when they started to see similar rashes in some Covid-19 patients
Raffaele Gianotti, a dermatopathologist with the University of Milan, said Sars-CoV-2 – the virus which causes Covid-19 – had been found in the 25-year-old woman’s preserved skin tissue. She was misdiagnosed with a rare autoimmune disorder, but could now be Italy’s “patient zero”.
“Our patient could represent the oldest case in literature of detection of the virus on tissue samples,” Gianotti and his collaborators from Spain and Britain said in a peer-reviewed paper published in the British Journal of Dermatology last Thursday.
“Could this case be Italy’s patient zero?”
According to the researchers, the woman had a sore throat but no other symptoms and a thorough examination gave no clue as to the cause of the skin irritation. Her doctors drilled into the rash and obtained a core sample of skin tissue. Finding nothing, they refrigerated the sample.
It was not until July last year, as the first wave of the pandemic swept across Europe, that they recalled the mysterious rash, which looked similar to what they were seeing in some of their Covid-19 patients. Numerous studies by researchers in Italy and elsewhere have shown the virus can cause a rash.
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Initially, the woman was thought to have lupus erythematosus tumidus, a serious disease which causes the immune system to attack healthy tissue. Usually, recovery from the condition takes two or three years, but by April 2020, her rash had disappeared, adding to the mystery of her condition.
The woman tested positive for Covid-19 antibodies in June and, a month later, the doctors retrieved the stored skin sample. Testing was a challenge, as the concentration of any coronavirus present would be too low for a conventional polymerase chain reaction (PCR) kit to detect.
The Italian team used another method, known as RNA FISH, which releases fluorescent molecules that hook specifically to the coronavirus gene and is sensitive enough to detect the presence of a single copy of the virus.
Under the microscope, the researchers saw a “clear, strong” sign of the virus. To double-check their results, they treated the skin tissue with a chemical stain that changes colour on contact with a unique protein that forms the core of the novel coronavirus. The result was again positive.
The matched results from two different techniques left little room for doubt, but Gianotti wanted to be sure, so the team repeated the experiments on control samples – using tissues stored from 2018 for the negative group and samples from Covid-19 patients in intensive care units for the positive.
The second round of tests confirmed the results.
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Previous research in Italy has shown that a boy who was sick in November 2019 had a viral strain which was a 100 per cent genetic match with the virus later isolated in Wuhan, as well as other strains in circulation.
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Blood samples of more than 100 participants in an Italian lung cancer screening programme dating back to September 2019 were also found to contain antibodies which bind specifically to the Sars-CoV-2 virus. These patients were either without symptoms, or misdiagnosed with other diseases such as measles.
A researcher at the Centre for Life Sciences, Peking University said commercial PCR tests might not be able to detect the virus in skin samples, but some laboratories had developed improved versions which required fewer viral copies.
“If they can have a result both PCR and FISH positive, it will be rock solid,” he said.
