“Lock down the village, test everybody, and isolate the positives. It really works,” Andrea Crisanti says.
Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
Andrea Crisanti was on a 30-hour flight from Italy to Australia for a conference on 22 February when some disturbing news appeared on his phone. Italy had just had its first COVID-19 death, and more cases were accumulating fast. He asked conference organizers to move his talk to the first day, and made the grueling trip back home after that. “It’s something I do not recommend,” he says.
Crisanti, head of the microbiology department at the University of Padua, already knew trouble was coming and had geared up his lab to do large-scale testing for the new coronavirus. As it began to devastate his nation, Crisanti put his university and region at the forefront of the fight with an all-out campaign of testing and quarantine, even when that meant defying conventional wisdom.
Voices of the pandemic
A soft-spoken 65-year-old with graying hair and soft brown eyes, Crisanti has a matter-of-fact way of stating his opinions—even when he opines that something is “bullshit.” “He’s an innovative person who knows his own worth and has confidence in his judgments,” says Jules Hoffmann, a Nobel Prize winner and professor of integrative biology at the University of Strasbourg. His decisiveness helped rein in his region’s outbreak and show the rest of Italy how to tame the virus, which hit the country early and hard.
Crisanti, who trained in immunology and biotechnology in Rome before spending 25 years at Imperial College London, was used to fighting another scourge: malaria. Last fall, the University of Padua recruited him to continue his research on genetic strategies to block mosquito reproduction. But when news about the coronavirus began to emerge from China, Crisanti immediately shifted his focus.
In late January, when Chinese scientists published the genetic sequence of the new coronavirus, Crisanti began to test university students returning from China, symptomatic or not. He had conducted a few hundred tests when the regional health department told him to stop. Guidelines from the World Health Organization and Italy’s National Institute of Health said to test only patients with symptoms, he was told. Crisanti says the restriction made no sense: “I know very few infectious diseases where asymptomatic people do not play a major role.”
That’s where things stood when he got word of the first Italian COVID-19 fatality. The patient was from Vo, a prosperous village in the region of Veneto, about 50 kilometers west of Venice. The region’s governor ordered a 2-week quarantine of the town and testing of almost all 3300 residents. Anyone who tested positive was put on lockdown.
At the time, anecdotal reports were emerging from China about asymptomatic transmission, but no one had produced definitive evidence. Crisanti saw Vo as an ideal place to conduct an epidemiological experiment: a small population, universally tested, whose progress could be monitored closely. He got approval to retest everyone in the village 9 days after the first round of testing.
The numbers confirmed his thinking about asymptomatic transmission. In the first round of testing, 73 residents were positive for the virus. More than 40% of them had no symptoms yet had levels of the virus similar to those who were visibly ill. The Vo study also confirmed that isolating people helps stem transmission. Everyone who had tested positive was confined to their home, regardless of whether they had symptoms. By the second round of testing, a week and a half later, the number of positives had dropped to 29; they, too, were isolated. A third round of tests 2 months after the second found no positive cases.
“If you want to eliminate a cluster you have to lock down the village [or neighborhood], test everybody, and isolate the positives,” Crisanti says. “It really works.”
Crisanti persuaded the regional government of Veneto to test anyone with even the mildest of symptoms, and to trace and test their contacts as well. The effort targeted medical personnel and essential workers, such as supermarket cashiers. It helped that Veneto has a long tradition of taking strong public health measures, dating back to the invention of the quarantine during the 14th century plagues. (The word “quarantine” is derived from the word for “40 days” in an old Venetian dialect—the period for which incoming ships had to anchor in the harbor to avoid bringing in plague.) The region’s infrastructure was ready for a pandemic, with a health care policy that emphasizes decentralized primary care. In this case,that meant sending well-equipped nurses to test people at home or admitting them to small local hospitals with dedicated COVID-19 units.
In contrast, neighboring Lombardy, the prosperous region in which Milan is located, has emphasized large, urban hospitals offering first-rate surgical and specialty care. That system backfired in the pandemic, funneling sick people into the hospitals, which in turn became sources of infection. Lombardy became the worst affected region of Italy, with 2.5 times the number of cases and four times the number of deaths per capita as Veneto.
From the beginning, Crisanti was prescient. In late January he ordered enough reagent to process half a million swabs; then had his lab analyze the reagents and begin to produce its own. Thus, when other regions were running short, Veneto had a surplus of reagents. Later he ordered a piece of equipment that could process tests at high speed, tracking down a demo machine in London when he couldn’t procure one through the usual means because of heightened demand from the pandemic. “We got the only one in Italy,” he says. The machine quadrupled his laboratory’s throughput to more than 6000 swabs per day. Along the way, Veneto became an example of the value of extensive testing, tracing, and isolation—and ensuring the means to do it.
Newspapers hailed Crisanti as the “father of the swabs,” and the “rebel scientist,” for his defiance of official policy in the early days of the pandemic. He received the Lion of Veneto award for his service to the region, the seal of the city of Padua, and was honored by a special concert in Vo. Yet it hasn’t all been smooth. As the outbreak began to abate, the region’s governor, Luca Zaia, downplayed Crisanti’s contribution in comments to the press and claimed that he and his government deserved credit for taming the virus. Eager to reopen Veneto for tourism, Zaia became irritated by Crisanti’s insistence to go slow and turned to other scientists for advice. The freeze-out became so severe that in July, Crisanti said he would resign from the region’s advisory board, only to be talked out of it by colleagues and admirers.
Now, there’s a truce between the scientist and the politician. “It may have been a joint effort,” says Antonio Cassone, professor emeritus of medical microbiology at the University of Perugia. “But Andrea proved essential.”
Moving forward, Crisanti is analyzing the genetic and blood samples his team collected during the Veneto outbreak to learn more about individual susceptibility and antibody response. He remains undaunted by his encounter with politics. “The most important thing is to convey simple, clear, and honest messages,” he says. “And if you don’t know something just say it openly. People need to know the truth.”
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