One meeting in Boston seeded tens of thousands of infections, study finds

On Feb. 26, 175 executives at the biotech company Biogen gathered at a Boston hotel for the first night of a conference. At the time, the coronavirus seemed a faraway problem, limited mostly to China.

But the virus was right there at the conference, spreading from person to person. A new study suggests that the meeting turned into a superspreading event, seeding infections that would affect tens of thousands of people across the United States and in countries as far as Singapore and Australia.

The study, which the authors posted online Tuesday and has not yet been published in a scientific journal, gives an unprecedented look at how far the coronavirus can spread given the right opportunities.

“It’s a really valuable study,” said Dr. Joshua Schiffer, a physician and mathematical modeling expert who studies infectious diseases at the Fred Hutchinson Cancer Research Center in Seattle and was not involved in the research.

Schiffer said that the new genetic evidence fit well with what epidemiologists and disease modelers have been learning about the coronavirus. The Biogen conference, he said, was just one of many similar events that amplified and spread the virus in its early months. “I don’t think it’s a fluke at all,” he said.

The results came out of a project that began in early March at the Broad Institute of Harvard and Massachusetts Institute of Technology, a research center specializing in large-scale genome sequencing. As a wave of Covid-19 patients crashed into Massachusetts General Hospital, the Broad researchers analyzed the genetic material of the viruses infecting the patients’ cells. The scientists also looked at samples from the Massachusetts Department of Public Health, which ran tests around Boston at homeless shelters and nursing homes. All told, the scientists analyzed the viral genomes of 772 people with Covid-19 between January and May.

The researchers then compared all of these genomes to trace where each virus came from. When a virus replicates, its descendants inherit its genetic material. If a random mutation pops up in one of its genes, it will also get passed down to later descendants. The vast majority of such mutations don’t change how the virus behaves. But researchers can use them to track the spread of an epidemic.

“It’s kind of like a fingerprint we can use to follow viruses around,” said Bronwyn MacInnis, a genomic epidemiologist at the Broad Institute.

The first confirmed case of the coronavirus in Boston turned up Jan. 29. The patient had traveled from Wuhan, China, and his virus carried distinctive mutations found in Wuhan. But MacInnis and her colleagues didn’t find any other viruses in Boston from later months with the same genetic fingerprint. It’s likely that the patient’s isolation prevented the virus from spreading.

But as February rolled on, the researchers determined, at least 80 other people arrived in Boston with the virus. Undiagnosed, they spread it to others.

Most of the viral lineages in Boston have a genetic fingerprint linking them to earlier cases in Europe, the study found. Some travelers brought the virus directly from Europe in February and March, whereas others may have picked up the European lineage elsewhere in the northeastern United States.

MacInnis and her colleagues took a detailed look at a few key places to see how the virus swept through the city. At Massachusetts General Hospital, for example, they found that coronaviruses in patients did not share many of the same mutations. That was a relief, because it meant that the hospital was not a breeding ground where a single virus could spread quickly from patient to patient.

But that’s exactly what happened in a skilled nursing home where 85% of patients and 37% of the staff were infected. The researchers identified three different virus lineages in the home, but one of them accounted for 90% of the infections.

Such superspreading events are a hallmark of the coronavirus. When an infected person shows up in the right place — generally inside, with poor ventilation and close contact with other people — the virus can infect a lot of people in very little time. These unfortunate events don’t happen often, and so most people who get infected with the coronavirus don’t pass it on to anyone else.

The virus that raged through the nursing home didn’t spread beyond its walls, as far as MacInnis and her colleagues could tell. But when the virus showed up at the Biogen conference, the story turned out very differently.

The researchers were able to sequence 28 viral genomes from people at the meeting. All of them shared the same mutation, called C2416T. The only known samples with that mutation from before the Biogen event came from two people in France on Feb. 29.

It’s possible that a single person came to the meeting from Europe carrying the C2416T mutation. It’s also possible that the virus carrying this mutation had already been in Boston for a week or two, and someone brought it into the meeting.

As the attendees spent hours together in close quarters, in poorly ventilated rooms, without wearing masks, the virus thrived. While replicating inside the cells of one meeting attendee, the virus gained a second mutation, called G26233T. Everyone who was subsequently infected by that person carried the double-mutant virus.

From the meeting, the researchers concluded, this lineage spread into the surrounding community. In a Boston homeless shelter, for example, researchers found 51 viral samples with the C2416T mutation and 54 with both mutations.

“We had no idea it would be associated with the conference,” MacInnis said. “It came as a complete surprise.”

The researchers estimated that roughly 20,000 people in the Boston area could have acquired the conference virus.

New York saw a similar pattern, according to Matthew Maurano, a computational biologist at NYU Langone Health. After many viral strains arrived from Europe in February, a few came to dominate the city. “A lot of lineages die off, and some spread enormously,” Maurano said.

The Boston double-mutant spread particularly far. Researchers identified this lineage in samples collected later in Virginia, North Carolina and Michigan. Overseas, it turned up in Europe, Asia and Australia.

Dr. Jacob Lemieux, a co-author of the new study and an infectious disease physician at Massachusetts General Hospital, said it was impossible at the moment to determine how many people acquired the virus in the months after the Biogen conference. But it would be in the tens of thousands.

Six months after the conference, MacInnis said that it should serve as a warning to anyone who thinks life can return to an unmasked version of normal before the virus is brought under control.

“One bad decision can affect a lot of people,” she said. “And the ones who suffer the most from that reality are the most vulnerable among us.”