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Phylogenetic Analysis Shows How Superspreader Events Fueled SARS-CoV-2 Pandemic

NEW YORK – A phylogenetic analysis of early SARS-CoV-2 cases in Boston underscores the effect of superspreading events in the transmission of the virus.

Spread of the virus has been linked to workplace and social gatherings as well as to close living environments like nursing homes, and superspreader events in which one individual infects many others are also suspected to contribute to COVID-19 transmission.

One of the first outbreaks of COVID-19 in the US occurred in Boston. By sequencing and constructing phylogenetic trees for more than 700 cases from this outbreak, researchers led by the Broad Institute's Bronwyn MacInnis reported there were multiple introductions of SARS-CoV-2 into Boston, but that two chance superspreading events enabled the virus to gain a toehold. 

"[T]his study provides clear evidence that superspreading events may profoundly alter the course of an epidemic and implies that prevention, detection, and mitigation of such events should be a priority for public health efforts," MacInnis and her colleagues wrote in their paper, which appeared Thursday in Science.

The researchers generated 778 complete SARS-CoV-2 genome assemblies from 772 individuals and 72 additional partial genomes from samples collected between March 4 and May 9, 2020 by the Massachusetts Department of Public Health and Massachusetts General Hospital. The viral genomes were assembled using the Wuhan-Hu-1 sequence as a reference and used to construct a phylogenetic tree. The researchers developed additional trees that incorporated data from the Global Initiative on Sharing All Influenza Data (GISAID), which also includes SARS-CoV-2 data.

With this data, the researchers began to tease out when SARS-CoV-2 arrived in Boston and how it spread. In particular, they noted more than 120 putative viral introductions into the region. MacInnis and her colleagues noted, though, that most of the cases in their dataset are linked to just a few viral introductions. 

One early superspreading event took place at an international business conference in Boston in late February. The researchers sequenced viral samples from 28 people who attended the meeting, and all belonged to C2416T viral lineage. The parent lineage of C2416T, they noted, was widespread in Europe in January and February 2020, and before early March the C2416T lineage was only noted in GISAID in two French patients, suggesting there was low-level C2416T transmission in Europe before it was introduced in Boston and was transmitted through the superspreader event.

Another variant, known as G26233T was also linked to the conference and was found in about a quarter of the viral samples from attendees, suggesting it emerged at the meeting.

The C2416T lineage then spread throughout Boston and accounted for between 30 percent and 46 percent of viral genomes from the study period. The lineage also traveled further afield, the researchers noted, as by November 2020, viruses with C2416T could be found in 29 US states. The C2416T/G26233T sublineage, meanwhile, has spread to 18 US states and to Australia, Sweden, and Slovakia.

While the conference, which took place before many public health precautions were adopted, was linked to about 100 direct cases, the researchers estimated that about 50,000 diagnosed cases of SARS-CoV-2 resulted from meeting-linked viruses.

Another cluster of cases in the Boston area at the time was uncovered in a skilled nursing facility. The 83 SARS-CoV-2 genomes analyzed from there all formed a single cluster that was part of the G26233T lineage. Limited genetic variation among the samples also indicated a superspreader event there. Virus spread outside the facility, the researchers noted, was limited as it occurred later into the pandemic and among an isolated population.

Smaller clusters also later arose at the nursing home despite infection control policies, but led to little spread. 

Other case clusters arose in homeless shelters in Boston — with two of those clusters descending from the conference-linked C2416T lineage — and at MGH. 

According to the researchers, their findings indicate that superspreading events can have an outsize role on an epidemic. "[The analysis] illustrates the role of chance in the trajectory of an epidemic," they added. "A single introduction had an outsize effect on subsequent transmission because it was amplified by superspreading in a highly mobile population very early in the outbreak, before many public health precautions were put in place."