NEW YORK – In a keynote address to begin a virtual American Society for Microbiology Microbe conference on Monday, Deborah Birx, the response coordinator for the White House coronavirus task force, urged labs to expand SARS-CoV-2 diagnostic testing in the US through sample pooling and community engagement.
The COVID-19 pandemic is defying expectations in three surprising ways, Birx said. It is differentially impacting high-income countries, showing unexpectedly high levels of asymptomatic spread, and it is dramatically underscoring pre-existing socio-economic and health disparities.
The fact that the highest number of cases and mortality rates for COVID-19 have been in high- and upper middle-income countries has been surprising because a global respiratory epidemic had been projected to be particularly damaging to low-resource settings, Birx said.
But, so far at least, the impact of COVID-19 to low- and middle-income countries has been less than was predicted on paper for a respiratory epidemic, she said. One reason for this, Birx suggested, might be that LMICs on average have younger populations that may experience less severe illness.
The amount of asymptomatic spread has also been surprising, she said. Monitoring the outbreak as it began to take off in Europe, she said the "explosive, logarithmic spread" suggested to her that there must be many lurking cases, so that an outbreak could go undetected until the disease reached vulnerable populations.
The degree to which health and social disparities in higher-income countries have been highlighted by the pandemic was also unexpected, Birx said. The highest hospitalization rates are among people with annual incomes of less that $25,000, she said, and the highest proportion of illness by ethnicity and race is among Hispanic populations.
"I am often struck by people who say 'Americans were following the stay-at-home orders,'" she said. Although that is partially true, "Fifty percent of Americans were still working. All of our essential workers were still working. All of the people who needed the income, and who were providing our healthcare, our food — our truckers, our mailmen — they were all still working, and all exposed by being out in the workforce every day."
In her address, Birx challenged the laboratorian members of ASM to now adapt their testing response to detect asymptomatic spread and mitigate disparities.
The US has been able to increase testing over the past three months from approximately 1,000 tests per day to more than 500,000 tests per day, she said.
Labs were initially asked to quickly bring on new assays, and they provided early alerts to shortages in swabs, transport media, and extraction kits, Birx said. "Those difficulties that you alerted us to resulted in the federal government engaging the Defense Production Act," she said, citing a mechanism that authorizes the US president to require companies to accept and prioritize government contracts in emergencies.
Birx, an HIV and global health researcher, was herself called up on March 2nd to head the US COVID-19 response from a deployment in sub-Saharan Africa overseeing implementation of the Presidents Emergency Plan for AIDS Relief, or PEPFAR. Globally, PEPFAR has been responsible for setting up nearly all laboratories in resource-limited settings, Birx said. "All of that was done in partnership with ASM," she noted.
Decades of dedication to developing lab testing for HIV, another RNA virus, has now enabled the COVID response. "It is that strong work that is leaving us now with these platforms available for testing."
That said, "We need innovation in testing, and I think it is more than just more platforms and more tests," Birx added. "Those of you who know me from PEPFAR know I never give a talk without asking for things. I'm asking you to really look at this issue of pooling."
The technique of pooling samples is frequently used in low-resource settings as a way to conserve diagnostic resources. Essentially, a few patient samples are mixed together and tested. If the result is negative, then all the patients are presumed to be uninfected. If the result is positive, then the patient samples are tested again individually.
"Pooling would give us the capacity to go from a half a million tests per day to potentially 5 million individuals tested per day," Birx said in her keynote address.
Although there are currently US states with higher rates of COVID-19 test positivity, overall the US has a 6 percent test positivity rate, "really opening up the opportunity to doing five-people pools, or even greater," she said.
Expanding testing through pooling could enable more frequent testing, and a surveillance strategy could, in turn, allow people to more safely return to schools and work, Birx suggested.
Improved pool testing methods have recently been described, and the US Food and Drug Administration offered new guidance on the technique last week, but Birx suggested that the method needs to be vetted for each different COVID-19 test and platform.
"I'm asking you all to look at that, platform by platform, to know how large the pools can be on Roche, versus the Hologic platform, versus the Abbott m2000 platform, versus the Cepheid platform, and all of the Thermo Fisher [Scientific] and BD platforms," she said addressing ASM members.
Birx highlighted that contact tracing in asymptomatic carriers can be difficult. "You have to do more proactive surveillance testing, where you go into communities that have their first hospitalization and really expand testing all through that community to find asymptomatic and mild cases."
She added that people don't know they are infected and can be unintentionally transmitting the disease. "We saw this with HIV and we see this with other diseases like chlamydia. Silent transmission occurs and has to be informed by different methodology than waiting for people to develop symptoms and come forward," Birx said.
Testing also needs to move out into communities to stop the spread of the virus.
"This is going to take all of us out of our comfort zone, out past LIM systems that are hospital-specific to LIM systems that can be shared across the US, [and] from being able to just work within your hospital to a broader community catchment that allows an interface on a daily basis between the community and the hospital," Birx said.
Adjusting testing to the health disparities will also require translating knowledge about science and how tests work to the communities most affected, so that individuals can see the value of testing proactively before they have symptoms, Birx said. She specifically suggested that labs tap Spanish-speaking staff to help clearly translate science for at-risk communities.
"I have always found that if the community is informed about the science, and understands why it is important, the community will respond to that knowledge and stop pandemics. We've seen it with TB, HIV, malaria, and Ebola — an informed community is a protected community."
For example, so-called essential workers who may live in multi-generational households with their elderly or at-risk family members need to be encouraged to get tested regularly.
"This is how we move forward — taking science to the community so that everyone understands how we can best protect one another by utilizing the information and capacity that we have today," Birx said. "If we use our innovation, our ability to pool samples, and our current capacity, we have no excuses to not dramatically expand testing," she said.
"There is a team working around the clock to make sure that you have swabs and transport media, because we know if we dramatically increase the number of tests per day you will need those," Birx said. "Work with us, and work with your research institutions and the platforms we have … and then help us to make sure that those tests are available."
She further asked labs to "help with getting the message out into the community by doing local news and going to virtual town halls and getting the community to understand why regular testing — what we would call surveillance testing rather than strictly diagnostic testing — is important to really be able to protect those most at risk for COVID-19."
Birx noted that even at current testing levels, an uptick in test positivity rates at the county level provides a reliable early signal that there will be a local increase in cases requiring hospitalization. Of the approximately 3,100 US counties, there are currently about 110 with test positivity rates and number of cases on the rise.
But the accuracy of that early signal is dependent on labs increasing testing locally. "It's not going to work as a signal if we're not keeping on expanding testing into the communities so we can see those inflection points early," Birx said. "That signal is so critical for us. It is why we ask for daily reporting, which I know is difficult for everyone," she added.
Going forward, "Everybody should be tested — we should not wait for symptoms to be tested," Birx said.
And, she noted that the lab input continues to be critical to managing the US COVID-19 response.
"Just know that I am only a phone call or email away, and it is only through on-the-ground experiences that we get to see what is absolutely needed, county by county, community by community, state by state, so that together we can control this pandemic."
Birx drew parallels between the COVID-19 and HIV, where diagnostic test development was just a part of a picture that also required scientists to engage with communities and activists in order to ultimately slow the spread of the disease. While thanking ASM members for all they have done to date, she also rallied them: "Get all of your laboratorians out there talking to the community about what these tests mean, what this means for transmission – you can be at the forefront of that communication!"