by Ashlea Morgan
Photos of CRAC serology testing volunteers (Tian, Chris, Barbara, and Rebecca) and lab technician, Magda, while working in Dr. Elhad Hod’s Clinical Laboratory at Columbia. Photo credit to Dr. Wen-Hsuan Wendy Lin and Dr. Chris Ricupero.
How do we know if we were infected with COVID-19 if our symptoms were very mild? Or had no symptoms at all? How do we know whether it is safe to venture out again? As I began to read more about it, serology assays, or antibody tests, jumped out at me as an answer.
Serology assays can indicate whether a person is producing SARS-CoV-2 antibodies and thus possibly able to re-enter public life with less risk of infecting themselves or spreading the infection to others. “We don’t [yet] know to what degree antibodies translate to immunity, but there’s likely a correlation,” Dr. Natalie Steinemann, Chief Project Manager of the CRAC Serological Testing Team told me. Additionally, serology testing could be used to identify patients that qualify as a convalescent plasma donor, that is, someone who donates their potentially protective antibodies to treat those who are still overcoming COVID-19.
With implications as vital as this, I was excited to learn that this antibody testing was already happening at Columbia. In the Clinical Laboratory of the Medical Director of the Advanced Laboratory Medicine, Dr. Eldad Hod, two Columbia M.D./Ph.Ds. in the Department of Pathology volunteered to lead the effort. Dr. Wen-Hsuan Wendy Lin, chief medical resident, and Dr. Sandeep Wontakal, medical resident, developed, carefully combed over, and optimized a highly-sensitive, ELISA-based antibody detection protocol. To ensure the protocol provided consistent results, Wendy and Sandeep carefully ran, then re-ran test samples in 12-hour shifts for five days.
Their dedication and meticulous work kick-started the effort to perform antibody tests on those who are at great risk for exposure to the virus: Columbia/New York Presbyterian (NYP) healthcare workers. As the need to scale up testing arose, CRAC became involved.
As one of the earliest CRAC members, Natalie has seen all the CRAC projects evolve since their start. However, she admitted, the serology testing project was the “coolest thing she’d ever heard of.” Natalie works as a neuroscience postdoc in the Shadlen lab in the Zuckerman Institute at Columbia studying how motor planning affects brain activity during decisions-making. Despite having “held a pipette [only] once in her life,” she saw the potential for serology testing to help society fight COVID-19 and she wanted to be a part of the project.
THE PROJECT BEGINS
Within days of its inception in late March, a solid plan of attack was developed: they would recruit, train, and deploy a crack (CRAC) team of volunteers to perform ELISA-based assays on patient samples, ensure quality control, and serve as a back-up (in case another volunteer couldn’t make it). The team would work together proceeding from one task to the next with perfect timing and pristine accuracy--like on an assembly line.
However, despite the quick start, the project was held up. Questions remained about the availability of resources and institutional approvals. Additionally, clinical assays like the serology test could only be performed by licensed, Clinical Laboratory Technologists who have years of rigorous academic training.
All the pieces began to line up when New York State responded to the pandemic by allowing trained, non-licensed scientists, to perform these tests within a CLIA-certified lab, like Dr. Hod’s lab.
By April 17, the lab had all the reagents, a validated process, and some of the robots to start automating the process. CRAC could now form their team of highly skilled researchers for serology testing.
“Have you ever thought to yourself, ‘I'm so good at pipetting... if only I could save lives and the American economy with my pipetting skills!’ Well... THIS IS YOUR MOMENT,” the recruitment email read. It continued, “This is an extremely serious endeavor… Thus, what we are looking for, more than anything else are applicants of serious character...”
Becoming a member of the CRAC Serological Testing team required potential volunteers to complete online lab safety training and a strict in-person pipetting assessment.
“We were told to show up at the High Throughput Screening core… they wanted to ensure we knew how to use a multichannel pipette accurately,” John Christin, a CRAC Serological Testing volunteer recalled.
“The results from the multichannel pipet test needed to have a [small] standard deviation [in order] to pass the test,” Tian Li, another Serological Testing volunteer,recalled of her experience. Although initially nervous, she drew up the solution to be quantified and placed it on the scale: “It was within the limitations. [Dr. Charles Karan, who directs the core and ran the pipetting “test”] said, ‘You can join [the team]. Good luck!’”
THE TEAM OF VOLUNTEERS COMES TOGETHER
“How many other times have you had people knocking on your door asking ‘Please let me work two 8-hour shifts [per week] for free?’” Natalie told me as she described the volunteers' earnest willingness to help.
Ultimately, 13 senior postdocs and researchers who had 5+ years of molecular training joined the CRAC serology testing team. They include Dr. John Christin, a postdoc studying bladder cancer; Dr. Barbara Corneo, who directs Columbia’s Stem Cell Core at CUIMC; Dr. Christopher Ricupero, an associate research scientist with a neuroscience background; Dr. Tian Li, a staff scientist in immunogenetics; and Dr. Rebecca Delventhal, a postdoc working on fruit fly genetics.
By April 20, the volunteer rotation schedule was set and the volunteers began working in the lab.
“At this moment, it seems like everyone is working together,” Barbara expressed. “It’s how science is supposed to work... It’s absolutely beautiful” and “a reminder of why I wanted to be a scientist... If only it were like [this] all the time,” she joked. Tian echoed this sentiment, “We complement each other... We are really happy to work with each other!”
During the downtime between steps, Chris shared that he also appreciated chatting about science and post-COVID life with fellow antibody testing volunteers as well as the Biobank volunteers who share the space. Tian similarly told me that she enjoys sharing new funding opportunities and research avenues for combating the virus with the volunteers she has met.
Now in early May, the CRAC serology testing volunteers reflected back on the previous few weeks: “One month ago this test didn’t even exist, and now… the science is progressing so fast.”, Barbara told me. Rebecca remarked, “Every day I go, they are changing the protocol a little bit and are beginning to automate the process so they are not relying on a rag-tag bunch of volunteers.”
THE ROBOTS TAKE OVER
To keep the operation running in April, it required 12-13 volunteers to staff the lab in 8-hour shifts, 6 days a week. Now that the robots are up and running, only 2-3 rotating volunteers are needed. Yet, overall the team members were happy to be replaced by automation.
“[If] it means they can run more tests and increase volume... I’m happy to be a cog in the wheel”, Chris insisted.
“A new machine was just delivered and this machine could substitute [for our] volunteer work. Altogether, four machines should be able to do everything from the beginning to the end of the process… When we do it manually we can do just a limited number of samples (maybe 150 per day), but [with] the machine we can do a lot more....,” Barbara said regarding the transition to near full-automation.
“If we can fully automate it… it will eventually provide really valuable information for Columbia as an institution and community,” said Rebecca.
All in all, the CRAC serology testing team has succeeded in processing over 1000 tests per week, and overall ~3000! Although the volunteers will no longer be needed soon, testing of blood samples from healthcare workers has now been established and is expanding to cover the needs of the entire Columbia community (as of May 14th). In thinking about the impact of the project moving forward, the team was hopeful.
“As soon as we are not here”, Chris remarked, “we are freed up to look into other scientific opportunities, like looking into the plethora of patient data building up from the serology testing”.
And as her academic career continues, Rebecca plans to teach her undergraduate students molecular biology from her hands-on COVID experience: “Hopefully they will remember what antibodies are and how to do an ELISA. As scary as the whole situation is, I am trying to focus on that as a silver lining.”
Combined with vaccine development, putative therapeutics, and increased viral testing (saliva tests may help), ramped-up serology testing and research on the role of antibodies is crucial to the global effort to combat COVID-19. Rebecca hopes (as do I) that research such as in situ viral assays with patient SARS-CoV-2 antibodies will be able to give us an answer to how much immunity antibodies provide. But, “a lot more research needs to be done.”
Many thanks to all of those working on the CRAC Serological Testing project (P7): Dr. Natalie Steinemann, Dr. Christopher Ricupero, Dr. Hui Wang, Dr. Irina Sagalovskiy, Dr. John Christin, Dr. Neda Masoudi, Dr. Rebecca Delventhal, Dr. Steve Sastra, Dr. Steven Cook, Dr. Barbara Corneo, Dr. Danielle Tufts, Dr. Ilenia Pellicciotta, Dr. Jaya Sarin Pradhan, Dr. Tian Li, and Dr. Eldad Hod.
I especially want to thank the serology team members that I interviewed: Natalie (@NatSteinemann), Rebecca (@BeckyDPhD), Christopher (@chrisricupero), John, Tian, and Barbara (@cscicolumbia). Also, thanks to all those who edited previous drafts of this post especially Dr. Natalie Steinemann, Dr. Barbara Noro, Dr. Chiara Bertipaglia, and Kelly Butler who read it in its roughest form.
Finally, I was struck by the wholehearted appreciation that each of the highly skilled volunteers had for their fellow volunteers and all those that helped in the ramp-up of antibody testing.
The CRAC Serological Testing team thanks the Director of the High-Throughput Screening Center at CUIMC, Dr. Charles Karan, who prepared and observed all three days of the practical skill demonstrations; and Dr. Wen-Hsuan Wendy Lin and Dr. Sandeep Wontakal, who led the serology effort from the clinical side. As echoed in each of the other interviews, Chris Ricupero said “I feel very fortunate to work hand-in-hand with physician-scientists, [Wendy and Sandeep] each day in this effort. It’s really been a privilege.”
-Post 5: If not now, when? If not us, who? Perspectives on Stepping Up During Dual Pandemics
-Post 4: Answering the call: CRAC Serology Testing Volunteers Join the Fight Against COVID-19
-Volunteer Profiles: An opportunity to “meet” some of the serology testing volunteers
-Post 3: The human scrub machine
- Post 2: Biobank volunteers process 15,500 samples
- Post 1: The CRAC organizational structure
Covid-19 has changed what matters.
The CRAC team was born as a grassroots response to a pandemic none of us has experienced in their lifetime. CRAC has now grown into a community of like-minded postdocs, students, faculty, and administrators, from across Columbia University - a diverse and inclusive ecosystem of talented individuals with a simple goal: support projects to address what matters now, the fight against covid-19.
These are the stories of how the CRAC ecosystem has evolved and continues to adapt to bring life to efforts that became bigger than the sum of their parts. These are also the stories of single individuals who continue to inspire others with their unheralded efforts.