>> Recording.
>> Welcome to Module 2.4, "Superspreading Event
in a Pre-symptomatic Population."
Here we use genetic epidemiology
to investigate a COVID-19 superspreading event
in a congregate care setting.
This presentation is part
of the COVID-19 Genomic Epidemiology Toolkit
from CDC's Office of Advanced Molecular Detection.
My name is Dr. Glenn Gallagher and I'm the division director
for molecular diagnostics and virology
at the Massachusetts State Public Health Lab.
This is the fourth of four case studies that we will review
to provide insights into how whole genome sequencing can be
used as an investigative tool in outbreak settings.
Be sure to check out the toolkit's other modules,
which include a combination of case studies
and training materials, to help get you started supplementing
epidemiology with genome sequence data.
In this module, we focus on a COVID-19 cluster
in a skilled nursing facility, or SNF,
in Boston, Massachusetts.
This 142-bed SNF serves short-term care,
long-term care, and memory units.
Mean resident age was 83 years and the minority, 28%,
of residents were male.
In the spring of 2020, the state selected this SNF to serve
as a dedicated COVID-19 rehabilitation center requiring
the relocation of all residents.
Although the SNF had not reported any confirmed
or suspected COVID-19 cases, the Commonwealth
of Massachusetts Department of Public Health recommended
that the facility conduct universal screening/testing
of all residents and staff before the residents
were relocated.
This recommendation was based on emerging reports
of asymptomatic SARS-CoV-2 spread
in congregate care settings.
In response, universal SARS-CoV-2 screening was
conducted in April of 2020.
The facility employed intensive infection-prevention measures
in response to COVID-19.
This included a strict visitation policy, daily symptom
and temperature checks for residents and staff,
strict masking policy with universal masking of staff
and mandatory masking of residents who left their rooms,
increased attention to hand hygiene,
and heavily restricted facility admissions policy.
Only three residents had been transferred into the facility
in the two weeks preceding the universal screening/testing.
Unexpectedly, the universal screening/testing revealed a
superspreading event.
The screening was conducted among reportedly asymptomatic
residents and staff.
In total, 194 persons were screened for SARS-CoV-2
by real-time PCR: 97 were residents and 97 were staff.
Overall, 61% of all persons tested positive.
Specifically, 85% of residents and 37%
of staff tested positive.
Nearly one-third or 31% of residents died two weeks
after the testing; 80% of these residents had tested positive.
Here we show a detailed timeline
of specimen collection among residents and staff
for real-time PCR testing.
Specimens were collected on three days: April 1st,
April 5th, and April 6th.
On April 1st, the nasopharyngeal, or NP,
swabs were collected for 97 residents of whom 52
or 52% tested positive.
Four days later, on April 5th, the 45 residents
who had tested negative on April 1st were retested and 31,
or 69%, tested positive.
On April 6th, NP swabs were collected from 97 staff
of whom 36, or 37%, tested positive.
To capture the genomic characteristics
of the superspreading event, whole genome sequencing,
or WGS, was performed.
Sequencing was conducted on specimens from 83, or 70%,
of the 118 total cases.
Upon examination
of the sequencing results revealed the rapid spread
suggesting a superspreading event that agreed
with the epidemiological data.
The majority, 75 of the 83,
or 90% of sequenced cases comprised a single cluster shown
here at the right, right here.
You can see that these genomes show very little genetic
diversity with short branches.
Fifty-nine genomes are identical.
For a single introduction with a high number of cases,
this is uncharacteristically low genetic diversity.
If we now look at these cases with the x-axis as the day
of specimen collection, we can see that the estimated date
of the common ancestor for this cluster is March 20th.
This data supports spread
of SARS-CoV-2 among reportedly asymptomatic persons.
Another observation we can make from this data is
that not all introductions led to rapid transmission.
Here on the right, you can see cases represented
as circles using a software called MicrobeTrace,
clustering by genetic similarity.
This cluster of cases here represents the tree
that we showed on the previous slides, but now we can see
that two other clusters exist with three cases each,
right here and right here.
Seeing these additional small clusters provides evidence
that multiple introductions occurred in the SNF
and that superspreading can dramatically influence
transmission dynamics, with most cases resulting
from one introduction.
Additionally, all three putative introductions occurred despite
the facility's implementation
of intensive infection prevention measures.
In summary, the observed genetic diversity
in the main cluster was strikingly low,
even for recent transmission with a single introduction.
This event might reflect a low genetic diversity
within the index patient, a superspreading event
where transmission to secondary cases occurred through events
such as unusually close or prolonged contact
of the index case to secondary cases,
or the index case having a very high viral load at the time.
It could also be a combination of these things.
Notably, very little onward transmission was observed.
This might be a result of the event occurring
in a relatively isolated population.
Key takeaways from this case study are one,
that intensive infection prevention measures are
essential, but they may be insufficient
for preventing all transmission.
Two, screening/testing of reportedly asymptomatic persons
for SARS-CoV-2 can identify early transmission
and this can help public health officials prevent
further spread.
And three, genomic sequencing
of this superspreading event revealed extremely low genetic
diversity, with one of three putative introductions resulting
in rapid spread.
A limitation to consider is that all residents
and staff were reportedly asymptomatic
and that some persons might have had unidentified symptoms.
We acknowledge Jacob Lemieux and colleagues
at the Broad Institute for their assistance with this case study.
Thank you.