Necessity is the mother of invention, and in the case COVID-19, grit and innovation. One great necessity in this fight has been the push to make more testing available. Like clinical laboratories across the nation, UR Medicine’s Clinical Microbiology Laboratory has overcome a series of setbacks to establish testing for SARS-CoV-2, the virus that causes COVID-19.
Thanks to a dedicated team of scientists and collaborators, the lab successfully went from having zero testing in place to providing results for 1,000 people a day in just two months.
Answering the Call
Flu season is one of the busiest for the lab, and it was just beginning to wind down in early March. But then, “COVID-19 didn’t give us much warning or time to prepare,” said Dwight Hardy, Ph.D., director of Clinical Microbiology (right).
At the onset of the pandemic, the Micro team was asked to develop a molecular test for detecting the virus. The effort was led by Nicole Pecora, M.D., Ph.D., the lab’s associate director, along with postdoctoral fellows, Andrew Cameron, Ph.D. and Jessica Bohrhunter, Ph.D., Hardy, and a group of medical technologists.
The team faced some immediate obstacles, like shortages in chemical reagents needed for testing, and lack of equipment. But after many days of long hours, they created a manual laboratory developed test (LDT) modeled after the CDC’s emergency use authorization (EUA). On March 16, the lab started testing and reporting its first patient results.
Due to instrument and reagent shortages and the manual nature of the LDT, the lab was only able to provide results for about 200 patient specimens per day. This limited testing capacity presented a stark dilemma: Who would get a test?
To address that challenge, URMC leadership brought together the Micro team and a host of other groups including Infection Prevention, Intensive Care, Emergency Medicine and others to develop testing criteria. They decided that testing would be prioritized for symptomatic inpatients and health care workers (whether or not they showed symptoms).
The goal? To help stop the spread of the disease a by identifying the COVID status of patients at the hospital for care, as well as any workers who were potentially exposed.
In about two weeks, the lab gradually increased the number of specimens it could test. Then good news came in the first week of April as the FDA gave approval to have SARS-CoV-2 testing run on an automated instrument, Roche Cobas 8800. “The Roche” is a state-of-the-art machine that was already being used to test for other infectious diseases. Because of its ability to run batches of tests at a time, this proved to be a game changer.
Instead of being forced to send specimens to commercial reference labs, all testing for SMH and its affiliates could now be performed in-house within 24 hours. This meant more patients could be tested to determine whether they were positive for COVID-19.
Compassion Behind the Scenes
The lab now performs over 1,000 tests per day and hopes to more than double that number. Shortages of test kits, reagents and specimen collection kits continue to limit the lab’s ability to increase testing volumes.
While each day is a new day when it comes to availability of resources, Hardy said supply chains appear to be slowly stabilizing. He added that in spite of the ongoing hurdles his team has faced so far, and potentially more on the horizon, he’s extremely proud of the Micro team for coming together to meet the challenges head on.
“All of us in the laboratory feel compassion for patients, their families and their loved ones and want to do the best we can as quickly as we can, to do our part in either the diagnosis or management of this particular disease,” he said. “I think that’s why people were so willing to step up to the plate, to be flexible and work long hours without being asked. They were dedicated to patient care and wanted to do their part in this unusual circumstance.”
Strong Memorial Hospital now requires all asymptomatic inpatients to be tested for COVID-19. It’s one thing to keep up with heavy clinical volumes as specimens for testing continue to increase. Lab teams are accustomed to this, even in non-pandemic times. But it’s another thing to do this work while under pressure to develop new and effective testing for the general public.
Since April, the Micro team has undertaken a second wave of test development – this time for a serological blood test to detect SARS-CoV-2 antibody, which would determine whether someone has had COVID-19 in the past.
Much like earlier discussions about who should be tested for the virus, Medical Center leaders are now finalizing the logistics of a what widespread serological testing would look like. Meanwhile, the Microbiology team is working hard to validate the test so it is more than 99 percent accurate.
While health leaders and scientists are eager to provide antibody testing as quickly as possible, they want to get it right. And since the virus is so new, it’s not yet possible to know from an antibody test whether a patient is immune to COVID-19 or how long immunity might last.
Antibody tests will be very useful in determining past infections in our community. The next chapter of the pandemic remains unknown, but Hardy says the lab is equipped and ready for what’s ahead.
“Our team has risen to unprecedented challenges that were un-predicted just a few months ago,” he said. “We realize that the challenges are not over, but we continue to do our part day-by-day to provide the best diagnostic testing possible for our patients and community.”
March 12: First positive COVID-19 case confirmed in Rochester
March 16: UR Medicine’s Clinical Microbiology Lab issues first patient test results. Due to manual nature of the test and limited testing resources, strict criteria is put in place for who can be tested.
April 3: Following FDA approval, UR Medicine Labs starts running automated testing on Roche 8800, which greatly increases test volume.
Mid-April: Testing becomes available for some asymptomatic patients, including nursing home residents, those with respiratory symptoms, and those coming for elective procedures.
May 13: Strong Memorial Hospital requires universal testing for patients that are admitted.
June 1: UR Medicine to begin antibody testing.
A watershed moment in life: A springboard to academic success. That is what pathologist, Dr. Mukesh Agarwal, calls the University of Rochester Medical Center, where he was a resident in the 1980s.
Today, Mukesh is a professor of pathology and medical education at California University of Science and Medicine’s (CUSM) School of Medicine in San Bernardino. We caught up with him recently to find learn more about what he’s been up to since his time in Rochester.
He did residency at URMC (AP/CP) from 1982-85. Subsequently, a chemical pathology fellowship at Cleveland Clinic Foundation.
After training, he spent over two decades at a newly opened Johns Hopkins Hospital affiliated to a new University medical school in the United Arab Emirates, where he held clinical and academic positions. He rose up the ranks to become Professor and Chair of Pathology. In 2017, he returned to the U.S. to take on his current role at CUSM.
His research focuses on diabetes, with more than 90 peer-reviewed publications. He has been on international panels to formulate the latest guidelines for gestational diabetes mellitus for the World Health Organization, WHO and the International Federation of Gynecology and Obstetrics, FIGO.
What are some things you remember when you look back at your time living Rochester?
Rochester helped me in more ways than I can count. I met some of the finest teachers, mentors, and colleagues there. I learned a panoply of life lessons. I have too many moments at Rochester that I treasure. It is – and will always be – a part of me. Rochester also taught me to bicycle along the canal and cook (being alone, I had to).
Were there any specific people who made an impact on you?
My mentor is Dr. Neil Blumberg, who I am still in touch with regularly. He unlocked my academic gene. Our work on transfusion immunomodulation changed medical practice. His great advice was, “Do not second guess what you have done.” I learned how to temper great academic success with humility from Drs. Dan Ryan and Anthony DiSantagnese. I learned from Dr. Thomas Bonfiglio how to relax despite being super busy and always looked up to Dr. Stanley Patton, my former chair.
Amongst the residents, Mark Mitchell’s brilliance bowled me over. His wisdom and aphorisms are beyond compare and I am honored to be regularly in touch with him. Bill Rodgers treated me like family when I was alone in Rochester. I cannot quantify my gratitude for his goodness. Each sumptuous dinner at his home was memorable. Steve Spitalnik and Glenn Ramsey were residents worth emulating. A quick story: When I was looking for external referees to evaluate my credentials for promotion, I emailed Mark Stoler after over a decade. He responded five minutes later. John Laczin visited me two times during my stint overseas. All in all, besides academia, I learned many lessons in goodness, tolerance, and ethics.
What’s it like being back in the U.S. after living and working overseas for so long?
Against all our plans, we moved back to California three years ago. It was ordained by The Fates, I suppose. Johns Hopkins overseas turned out an eclectic mix of cultures, from over 100 countries. It made us understand them better, become less judgmental, and more forgiving.
After two decades, much has changed in the U.S. Americans have become less trusting and more money oriented. Also, it is hard to decipher this new crop of millennials, students and otherwise. Growing up, we believed our professors, we did not question them. There seems to be little leap of faith in this generation.
When did you realize you wanted to become a pathologist? Was there any one experience or person who pointed you in that direction?
Like most things in my life, it was sheer serendipity. A strange trick of fate. For learning research, I tried pathology for a year. I discovered all the advantages: the happy personalities, the good mix of life balance, the teaching, the research. I was smitten – and there was no going back. The rest, as they say, is history.
What advice would you give young people looking to pursue a career like yours?
Do not overthink your life. Make lemonade when life gives you lemons. At the new Johns Hopkins overseas, there was a paucity of expertise, e.g., statistics. The ethos was different from my background. But diabetes prevalence was the second highest in the world. And pregnancy was rampant. So, I started working on gestational diabetes, which turned out to be a great hunting ground for research.
Do you have any hobbies you spend time doing outside of work?
Today, I believe I am quite a chef. I own more than 300 cookbooks. Overseas, we learned from different cultures, from Japanese to Italian to Serbian. I was always and am still passionate about English language and literature. I remain an avid cyclist. Ironically, we live in Redlands, CA. When I cycle to the nearby University of Redlands, I see huge posters with the initialism: U of R – a metaphor that the University of Rochester will always be a part of me. It is a de ja vu.
Tell us about your family.
My wife has a master’s in economics but was a home maker by choice. We have two adult daughters. Priya has a master’s in clinical therapy treating childhood trauma through play therapy. A niche field coming into its own. She went to Colgate University-a stones’ throw from U of R. Neha is starting college waiting for life to unfold. We live together, an un-American concept, but normal by Asian standards. It is a blessing to be so close together.
I am close to Upstate N.Y. My brother has been living in Binghamton for four decades. My daughter misses her alma mater, Colgate University at Hamilton, N.Y. So, I shall visit soon.
The American Board of Pathology (ABPath) has announced the appointment of Philip Katzman, M.D. to its Test Development and Advisory Committee (TDAC) for Pediatric Pathology for 2020.
The TDACs are responsible for developing and reviewing the ABPath certification exam questions that assess and certify a physician’s education, knowledge, experience, and skills in order to provide high quality care in the pathology profession.
To be appointed to a TDAC means a physician is an established subject matter expert in their subspecialty field and is current on the latest advances in the continually evolving field of pathology and patient care.
TDAC committee members develop and review examination questions for statistical performance and relevance to current practice. They contribute to the validity of examinations by determining the content and distribution of items on examinations (exam blueprints). The TDACs also advise the ABPath on issues in their subspecialty area of expertise.
“As TDAC members, these physicians play a critical role in the development of the exams and are entrusted with maintaining the integrity of the board-certified designation,” stated Rebecca L. Johnson, M.D., CEO of the American Board of Pathology. “The appointment to a TDAC indicates the physician is highly regarded in the field of pathology and exemplifies the utmost standards of care.”
Dr. Katzman earned his medical degree at the University of Vermont and completed AP/CP pathology residency and pediatric pathology fellowship training at the University of Rochester Medical Center and Boston Children’s Hospital, respectively. He is currently Professor of Pathology and Director of Pediatric Pathology in the Department of Pathology and Laboratory Medicine at URMC.
Since 1971, the ABPath has appointed test committees for each specialty area of pathology. The committee consists of ABPath trustees and other pathologists or specialty physicians who are recognized experts in their respective disciplines.
The University of Rochester Educational IT Governance Committee has awarded a grant to introduce the web platform Padlet Backpack into the curriculum for students at the School of Medicine & Dentistry and School of Nursing.
The nearly $13,600 grant funded by the committee and the Institute for Innovative Education will give students and instructors the chance to use Padlet Backpack as part of their class curriculum. If the program proves successful, the program could later be adopted University-wide.
The proposal was led by principal investigator Jennifer Findeis-Hosey, M.D., associate professor and instructor for the School of Medicine who was recently named Vice Chair for Education for Pathology & Laboratory Medicine.
Padlet Backpack is the institutional version of Padlet, a secure, web-based application that facilitates students and instructors extending curricular discussions outside of the classroom through the use discussion boards.
How will it work?
Medical students who participate in anatomy labs during their first year will have the opportunity to take tissue samples of areas of interest with macroscopic pathologic changes.
The same tissue will then undergo histologic preparation (a process carried out by professional staff in Surgical Pathology at Strong Memorial Hospital) so they can see the correlation between the macroscopic and microscopic pathology.
The “macroscopic” and microscopic photos can then be used in Padlet Backpack so the students and instructors can discuss a diagnosis based on what they see in the images. Key to these discussions is learning how to recognize what’s normal and what could be visually indicative of disease – which is exactly what a pathologist does.
“I think from the pathology side, it’s nice because it helps emphasize what pathology does,” said Findeis-Hosey. “It gives us a space to interact with medical students early in their medical education training.”
The School of Nursing will use Padlet Backpack in its Management of Care Course, which is one of the final courses in its accelerated program for non-nurses. Rather than using photos, the platform will serve as a place for discussion and brainstorming for class projects.
The grant began Jan. 1, 2020 and instructors plan to have the application in their curriculum for the fall.
Co-P.I.’s on the grant include Martha Gdowski, Sarah Peyre, Tara Serwetnyk, Marjorie Shaw, and Andrew Wolf.
As the number of vaping-related illnesses continues to climb in the U.S., pathologists who diagnose lung injuries as part of a larger healthcare team, say it’s not easy to see the signs of vaping under a microscope.
But that may be changing as scientists identify the visual cues common in patient specimens, whether or not they are forthcoming about their vaping habits. A new study published in the New England Journal of Medicine (NEJM) and reported in The New York Times compared vaping related lung damage to the same type of damage caused by chemical burns.
Moises Velez, M.D. is the director of the Thoracic Pathology subspecialty service at the University of Rochester Medical Center. He and fellow cytopathologists, Tanupriya Agrawal, M.D., Ph.D. and Ellen Giampoli, M.D. shared more about the ways in which vaping is showing up in everyday diagnoses, and how recognizing the signs can get patients help quicker.
What exactly does a thoracic pathologist do, and what do they look for?
Normal lung cells as seen under a microscope after staining, at 20x magnification.
Visible inflammation in lung cells of a patient known to have vaped (magnified at 40x).
Normal lung fluid magnified 40x.
Lung fluid (magnified 60x) of a patient with a history of vaping. The lipid or oil in the cells stain red with Oil Red O. This is presumably caused by vaping or inhaling an aerosolized oily substance.
Velez: A thoracic pathologist is a specialized doctor that diagnoses diseases of the thorax, or chest cavity, by looking at tissue or fluid specimens under a microscope. Hundreds of disease which fall into this category.
Have you ever encountered a case in which a patient had lung damage due to vaping?
Agrawal: To date, I have received four bronchoalveolar fluid specimens (BAL) that came from patients with a history of vaping. Each patient presented with signs of respiratory failure.
In recent months, I had a teenage patient who was admitted to the ED with respiratory failure. They had a history of marijuana use and couldn’t remember what they inhaled the day before, but had vaped a few months before.
What is known from the literature is that vaping can present acutely and up to 90 days. So if someone has vaped in the last 90 days, it can present later. Because of the history for vaping, the patient was treated with steroids and antibiotics and later discharged.
Why is it difficult to know what damage is caused by vaping?
Velez: Recent literature in the NEJM reported patterns of lung injury such as diffuse alveolar damage, organizing pneumonia, granulomatous pneumonitis and foamy macrophages in patients with a history of vaping. We know these patterns of lung injuries described are not specific to any disease process.
For example, they can also be seen in an infection, sepsis, drug toxicity, toxic inhalation, and collagen vascular disease to name a few. If the history of vaping is known, Oil Red O may be performed to identify lipid in macrophages. Knowing the clinical history is the key make the association of vaping and lung injury.
Aren’t there other methods, like CT images, to detect a lung injury that could be vaping-related?
Velez: Clinicians suspect lung injury if someone has been inhaling something recently (such as e-cigarette vapor) and they develop shortness of breath and come to the ED. Then they may undergo a chest CT. The radiologic findings are not specific and show patterns that can correlate with eosinophilic pneumonia, diffuse alveolar damage organizing pneumonia and lipoid pneumonia. The history of inhalation coupled with the radiologic and histologic evidence of the lung injury, means you can suspect this was due to vaping.
In other words, a pathologist can probably tell a person is sick because of vaping, based on what they see under the microscope, but unless you know from the patient’s doctor that they vape, you can’t link the two?
Agrawal: Correct. If we are not provided with the patient’s history, it’s just an acute lung injury for us. Maybe the patient has an infection, but unless a history or clinical report is provided or there is some clinical suspicion, we as pathologists cannot make a determination.
Do you think patients don’t want to disclose that they’ve vaped for fear of stigma, or that they’ll be punished for doing something illegal (especially if they vape an illegal substance like marijuana)?
Velez: It’s uncertain if vaping carries any stigma at all, but it’s possible that youth may conceal their habits. There are over 2,000 flavors of vaping cartridges, so it’s enticing. The nicotine vaping cartridges also contain as much nicotine as a pack of cigarettes. None of this is FDA-regulated.
Agrawal: With teenagers especially, they want to experiment with vaping and mixing edible oils so nobody knows exactly what they’re inhaling, how it’s being transformed as it goes into the lungs. There is no research out yet on this.
Some see vaping as an epidemic. What’s one practical way clinicians can help fight it?
Giampoli: Our physicians and ER docs on the front lines need to get nosy and ask patients if they vape. At the moment there’s nothing specific for us to identify it with until we see more cases and can identify patterns in what we’re looking for.
Our whole job is finding patterns with the information we have. We will be able to recognize these cases faster, pick up these connections quicker, and hopefully be able to help our clinicians help these patients much more quickly.
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