Medical Laboratory Professionals work behind the screens of the medical industry. The contributions produced by this diligent, dynamic, accuracy-driven teams, provide approximately 70% of diagnostic information. This information is imperative for proper diagnosis and treatment. Due to the nature of laboratory work, laboratory personnels are not visible at the forefront of delivering patient care. Therefore, much of society is unaware of the efforts conducted within other parts of the medical industry.
In November of 2018, I had an experience with an elderly couple that will always remain at the forefront of my mind. I was an evening shift Blood Bank Technical Supervisor at a Trauma Level I hospital housing with more than 1000 beds. The Blood Bank served in/out transfusion-dependent patients, as well as being a transplant institution conducting cardiac, liver, and lung transplants. To say we were busy is an understatement.
We had an outpatient order for an older woman who was accompanied by her husband. Her husband, being her advocate, was known to express his concern regarding an issue concerning his wife. The patient’s two units of blood were delayed and the patient’s husband proceeded to call the blood bank to inquire about the delay. The medical laboratory assistant informing him the order was being worked on was not enough, so he proceeded to hound the nurse. The nurse then proceeded to ask to speak to the supervisor.
Before speaking to the nurse, I got the status of the order and asked the technologist approximately how much longer the wait would be. She explained intital testing had revealed an antibody, and so she followed protocol and informed the nurse there would be a delay in blood products.Completing the workup and finding appropriate blood for the patient is what caused the delay. She was at the last portion of crossmatching the blood, and after my review of the workup, it should be 15 minutes.
I informed the nurse it would be 15 minutes, and she pleaded with me to explain the delay to the patient and her husband. After receiving confirmation from my manager to proceed, I hand-delivered the blood to the outpatient room.
“Perception is reality,” so it is imperative to be aware of all verbal and nonverbal communication when interacting with patients. Therefore, accompanied by the nurse, I entered the room and introduced myself and my position. I explained in layman’s term an ABO Type, antibody screen, and finding suitable blood when an antibody has developed. When I was through, they had an exceptional understanding of concept and turnaround time. The patient and husband were appreciative of my explanation and grateful for my staff. The patient’s husband then asked me about my education and what it entailed for me to hold my position. He was highly impressed and never knew all the science and math courses required to become a medical laboratory scientist. He said it was an opportunity he was going to pass along to his granddaughter, who was interested in science.
The following day, the patient’s husband called and apologized to the staff member he initially spoke with and praised the work we do for all patients. This experience highlighted the importance of training laboratory management when interacting with patients. It is more common for the pathologist or medical director to reach out to patients but there are times, especially on the off-shifts, where a laboratory supervisor or manager may be the best option available.
Being an advocate for the medical laboratory science profession is a means of educating the society of a vital career which impacts all lives. Medical laboratory lrofessionals may be behind the scenes, but to administer treatment, essential laboratory results are required; without the laboratory – you’re guessing.
-Tiffany Channer, MPH, MLS(ASCP)CM honed her skill and knowledge of Blood Banking at Memorial Sloan Kettering Cancer Center in New York, NY, where she completed her 9 year tenure at Memorial Sloan as Blood Bank Educational Lead Medical Technologist III/ Safety Officer. She’s currently working as a Quality Assurance Specialist / Educational Supervisor at Memorial Sloan Kettering Cancer Center. Tiffany was a Top Five 40 under Forty Honoree in 2015 for her dedication and advocacy to education and laboratory medicine.
When I first thought of writing a blog on blood supplies amid the COVID-19 pandemic, it was early March. Fast forward a couple months and a lot of things have changed. So, where were we, and where are we now?
January 6, 2020
At this time, most people in the US were not even aware of the novel coronavirus. (unless you were taking my Introduction to Human Disease course and were searching online for media articles about infectious disease!)
I first became aware of this ‘mystery’ virus in early January, when I was teaching an online Winter session course called Introduction to Human Disease. I developed this course a number of years ago as a STEM course for non-science majors. The intent of the course is to familiarize students with diseases and disease terminology that they will use in their everyday lives. The course gives students a chance to learn basic medical concepts that will enable them to become their own (or their family’s) medical advocate. In addition, the course covers many diseases that are ‘in the news’ and allows students to gain some knowledge and insight into the myths and facts surrounding these diseases. Topics covered include general mechanisms of disease, including inflammation, infectious disease, immunity, heredity, and cancer. Emphasis is placed on emerging and pandemic …. so, when this disease emerged, we were right there to take note!
I asked the students to find an article in the media on an infectious disease, and to summarize and answer questions about the article and the mechanism of the disease. Three students chose different articles about this yet unnamed mystery illness affecting people in Wuhan, China. We had active discussion board conversations about this emerging severe respiratory disease and pneumonia, that at the time had infected around 40 people, with no reported deaths, and no human to human transmission. In my comments, I compared this novel virus to seasonal influenza, H1N1, SARS and MERS and tried to reassure students that this would hopefully follow the same path as H1N1 or SARS and MERS.
Feb 21, 2020
The first confirmed case in the United States was on Jan 21 in Washington state. (CDC)1 On Jan 31, the Health and Human Services Secretary declared Coronavirus a Public Health Emergency in the US. (HHS.gov)2 We began hearing news of restrictions on flights from China, passengers affected on Princess Cruise ships and outbreaks at a long term care facility in Washington State.
As a Medical laboratory Scientist, I became concerned with this virus early on, and started watching statistics. I was concerned not only for the health of my family, friends and coworkers, but also for the health or our laboratories and our blood supply.
The first journal articles I read about COVID-19 and blood safety were published in Transfusion Medicine Reviews on Feb 21, 2020. In the very early days of this novel coronavirus, researchers in China reviewed publications about SARS and MERS to help give us a better understanding of SARS-CoV-2, the virus that causes our current pandemic of COVID-19. When discussing blood safety, one of the first things to consider is if the virus is transmittable via blood transfusions. If the virus is transmittable, we also must consider if there is an asymptomatic time when there is virus in the blood. One review stated that SARS, MERS and SARS-CoV-2 can all be found in the serum or plasma, but, at the time of this review, it was still uncertain if SARS-CoV-2 could be transmitted from those with pre-symptomatic or asymptomatic infections.3
March 18, 2020
On March 18, Blood Transfusion published an article written by a group at several Blood Centers in a few provinces in China. This article discussed efforts to minimize the impact of blood shortages due to COVID-19. It was noted that the rising pandemic had had a profound impact on the number of blood donations, and on blood safety. Because it was now recognized that there is a long incubation period and a significant number of asymptomatic cases, this posed a huge challenge in recruiting blood donors. In China, strictly restricted mobility led to a decrease in donations across the country. Donors were recruited through various methods, including the use of social media. Social distancing during blood donations and thorough cleaning and disinfecting of donor areas were enforced. Screening procedures were enhanced to include temporary isolation of blood products for 14 days after collection and delaying release for clinical use. At the same time, donors were followed up until the expiration of the products. If a donor was found to test positive for COVID-19 after donation, the blood products were recalled. These new protocols in place were helping to insure adequate donations and the safety of blood products. ne interesting note is that this article referred to the epidemic as “effectively controlled” and that “normal medical services had been resumed”.4
Meanwhile, in the US, American Red Cross was pleading for blood donors. On March 17 it was reported that 2,700 mobile blood drives had been cancelled at a loss of 86,000 units of blood potentially collected. On March 21, 4 days later, that number had risen to more than 5,000 blood drives canceled at a loss of 170,000 units. As more schools, workplaces, churches and college campuses closed down in response to the pandemic, those institutions had to cancel their blood drives. Social distancing guidelines and shelter in place orders resulted in fewer people donating blood. In addition, an FDA mandate from February, that people who had traveled to areas with COVID-19 outbreaks should wait at least 28 days before donating blood, most likely contributed to the shortage. Dr. Justin Kreuter, from the Mayo Clinic Blood Donor Center, stated that the blood shortage was not due to more COVID-19 patients needing blood products. Rather, “it’s a lack of donations coming in.”5
April 1, 2020
procedures that the Chinese had instated. Mobile blood drives were shut down, but collection centers remained open. TV commercials, radio ads, You Tube videos and social media called for blood donors, assuring them that this was essential and that donating blood was safe. Donations were arranged through appointments only, and potential donors contacted and verbally screened for symptoms and risk factors before appearing to donate. On arrival at the centers, temperatures were taken and travel and symptoms questions were asked before a donor was allowed to enter the center. The use of masks and social distancing, along with extra cleaning and donor chair decontamination between donors were all implemented.
In an effort to open up the pool of potential donors, the FDA reviewed current studies and epidemiological data and concluded that certain donor eligibility criteria could be modified without compromising the safety of the blood supply. On April 2, 2020 the FDA approved several important changes in donor qualifications. These revisions included the following:
For male donors deferred for having sex with another male: the recommended deferral period changed from 12 months to 3 months.
For female donors deferred for having sex with a man who had sex with another man: the recommended deferral period changed from 12 months to 3 months
The deferral period for recent tattoos and piercing was changed from 12 months to 3 months
For people who have traveled to malaria-endemic areas, the recommended deferral period was changed from 12 months to 3 months. In addition, the guidance notes that deferral can be waived for these donors, provided the blood components are pathogen-reduced using an FDA-approved pathogen reduction device.
For donors who spent time in European countries or on military bases in Europe who were previously deferred due to potential risk of transmission of Creutzfeldt-Jakob Disease or Variant Creutzfeldt-Jakob Disease, the FDA has eliminated the deferrals and these individuals may now qualify to donate.6
Despite loosening requirements, advertising, and calls from the blood centers for additional donors, the shortages remained. To address the decline in blood product availability, it became essential to review the principles of patient blood management (PBM). PBM is defined as “the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss in an effort to improve patient outcome.”7 Firstly, elective procedures were put on hold, thus freeing up units for the most needy patients. Despite this, many blood banks still had their standing orders decreased. In many cases, Blood bank Medical Directors approved changes in transfusion triggers. At the hospital where I work, the transfusion trigger was changed from a hemoglobin of 8g/dL to 7 g/dL. New changes of SOP were approved to issue to all patients, except females of child bearing age, Rh positive units instead of more scarce Rh negative units. We also have a large NICU unit and baby units were not available from ARC, so we were using the newest units available, when necessary for these patients.
By April 8, 15,000 blood drives had been cancelled across the US, at a potential loss of almost 500,000 donated units. One technologist reported in an online Blood bank professionals group, that “Our supplier downgraded us in terms of standard inventory (about 40%), but our transfusion numbers have dropped at least as much.”8 With the decrease in usage and the careful patient blood management, blood needs were met.
May 12, 2020
AABB began sending out a weekly COVID impact survey for hospital transfusion services survey in late March. Many questions on the survey, and the resulting charts and graphs, are related to COVID convalescent plasma practices and procedures (details in my next blog!), but one important graph produced by this survey shows the increase in inventory wastage due to changes related to COVID-19. These changes due to COVID-19 can be a decrease in patients and elective surgeries or changes in transfusion protocols. In early April, in the first few weeks of the survey, 25%-28% of hospitals responding reported an increase in inventory wastage. This corresponds to when donors started coming back to donate, and usage dropped. This percent of hospitals reporting wastage increased each week until the week of May 4-7 when 54% of hospitals reported inventory wastage. This may be due to several factors. The units collected at the end of March and early April, have reached their 42 day expirations. Donors came out initially in response to the call for blood, but now, these units have expired, and it has not yet been 56 days when these donors can donate again. Usage also decreased during this time. COVID patients have not generally had heavy use of red cells, in particular, and doctors have been very conservative in usage with all patients. For the week of May 11-14, as more hospitals are planning to resume elective surgeries, and for the first time in the 8 weeks, fewer hospitals (52.0%) reported an increase in wastage due to changes related to the pandemic. Of the 100 respondents, 59% reported they are resuming “some” elective surgeries before mid-May and 28.0% are doing so after mid-May.9
What does this mean for the future of our blood supply during this pandemic? On May 12, a group of Blood bank professionals, when asked in an informal online survey, had had varying answers. These were likely dependent on location, both geographic and city vs. rural, and size of the hospital. One comment was that “We have gone from huge shortages to throwing away massive units not being used. Hospital is empty.” Another tech said “We were way overstocked a week ago, now we’re dipping way below average.” Technologists in Florida, Oregon and Pennsylvania reported low inventory. Techs in Ohio and Maryland reported their inventory to be very healthy. But these reports could easily vary between areas of the individual state, and even different hospitals in the same city. Another technologist commented “We had a mass of donors when this all started and now all those units are expiring!” The shortage of donors will likely continue, but may relax a bit with some states beginning to lift restrictions. We likely won’t see a huge drove of donors, all at once, which is actually good because it will spread out expiration dates. But, though things may be opening up, it is unlikely that we will see blood drives at schools, workplaces and churches for some time, and this is a huge source of our countries blood supply.
We have seen a big swing in both inventories and usage. After elective and with surgeries have been put on hold for months, we may see an increase over the typical number of elective surgeries, which will mean we will see an increase in blood usage, and with a lack of donors, inventories may drop again.
As far as blood safety, we know now that SARS-CoV-2 did not follow the path of SARS and MERS. We know that it can definitely be transmitted from person to person, and can be transmitted by people who are asymptomatic. But, we also know that, in general, respiratory viruses are not known to be transmitted by blood transfusion. So, from what we know at this time, it is likely not necessary to routinely screen blood products for SARS-CoV-2, and not necessary to isolate blood products after collection and delay release of the products. It is recommended that blood centers encourage self-deferral for donors who have traveled to a COVID-19 affected area or been in contact with an infected person in the past 14 days and to screen donors carefully for fever and respiratory symptoms. With these practices in place, we can ensure an adequate and safe blood supply. We will continue to see swings in volumes, but with careful patient blood management, we will ride these waves and come out on top. Thanks to all our wonderful Blood Bank Technologists who are helping manage our country’s blood supplies!
-Becky Socha, MS, MLS(ASCP)CM BB CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.
Cytomegalovirus (CMV) is considered the most important pathogen in transplant recipient patients as it can cause significant morbidity and mortality. Anti-CMV treatments have proven to be effective but are not without adverse side effects. Thus, there is a strong need for sensitive and reliable tests to diagnose and monitor active CMV infection. Several testing methodologies are available in today’s clinical laboratories to evaluate a patient’s CMV status: viral culture, serology, histopathology, pp65 antigenemia, and quantitative PCR. In this post, we will review the advantages and limitations of these tests.
Viral culture is performed most commonly by the shell vial assay (also known as rapid culture), in which a cell line (usually human fibroblast cells) is inoculated with patient sample by centrifugation. The virus is then detected by either direct or indirect fluorescent monoclonal antibody, providing results within 1-3 days. The centrifugation step greatly improves turnaround time when compared to traditional tube cell culture technique, which may take 2-3 weeks before a result can be reported as negative.
Culturing CMV has been largely replaced by newer methodologies like quantitative PCR and CMV antigenemia. This is due to relatively weaker sensitivity for diagnosing CMV infection compared to newer tests, as well as slower turnaround time. Viral cultures of urine, oral secretions, and stool are not recommended due to poor specificity; however, for diagnosis of congenital CMV, viral culture of urine or saliva samples is an acceptable alternative if PCR is not available.
CMV serostatus is an important metric to evaluate prior to patients receiving a hematopoietic or solid organ transplant. Serologic testing is done primarily via enzyme immunoassays and indirect immunofluorescence assays. These tests check for presence of anti-CMV immunoglobulin (Ig)M and IgG to provide evidence of recent or past infection. Outside of establishing serostatus (primarily in organ donors and recipients), serologic testing for CMV is not recommended in diagnosing or monitoring active CMV infection.
CMV IgM antibodies can be detected within the first two weeks of symptom development and can be present for another 4-6 months. IgG antibodies can be detected 2-3 weeks after symptoms develop, and remain present lifelong. These antibody measurements are particularly useful in determining risk of CMV acquisition in seronegative patients (negative for IgM and IgG) at time of transplantation. IgG titers can also be measured every 2-4 weeks to assess for CMV reactivation in seropositive patients. Since CMV IgG persistently remains in circulation, testing for it has a higher specificity compared to IgM, and thus is the preferred immunoglobulin to test for in establishing serostatus. Serologic tests can be falsely positive if patients have recently received IVIG or blood products, so testing on pretransfusion samples are preferred if possible.
Under the microscope, cells infected with CMV can express certain viral cytopathic effects. These infected cells classically show cytoplasmic and nuclear inclusions (owl eye nuclei) with cytoplasmic and nuclear enlargement. Additionally, immunohistochemistry (IHC) can stain antibodies specifically for CMV proteins to highlight infected cells, making histologic examination quicker and improving diagnostic sensitivity.
Histopathology can be useful in identifying tissue-invasive disease, such as CMV colitis or pneumonitis. Cases in which PCR testing is negative does not necessarily exclude tissue-invasive disease; thus, the diagnosis of tissue-invasive disease relies on histologic examination (with or without IHC) or possibly viral culture. On the other hand, a negative histologic result does not exclude tissue-invasive disease, possibly due to inadequate sampling, and shows the potential for weak diagnostic sensitivity.
CMV antigenemia testing uses indirect immunofluorescence to identify pp65 antigen, a CMV-specific matrix protein, in peripheral blood polymorphonuclear leukocytes. Whole blood specimens are lysed and then the leukocytes are cytocentrifuged onto a glass slide. Monoclonal antibodies to pp65 are applied, followed by a secondary FITC-labeled antibody. The slide is then read using a fluorescence microscope for homogenous yellow-green polylobate nuclear staining, indicating presence of CMV antigen-positive leukocytes. Studies have suggested that a higher number of positive cells correlates with an increased risk of developing active disease. The sensitivity of antigenemia testing is higher than that of viral culture and offers a turnaround time within several hours.
This test has been utilized since the 1980s, but has seen less use recently due to the increasing popularity of quantitative PCR. Antigenemia testing is labor intensive, and requires experienced and trained personnel to interpret the results (which can be somewhat subjective). This test also must be performed on whole blood specimens within 6-8 hours of collection due to decreasing sensitivity over time, which limits transportability of specimens. Additionally, It is not recommended to be run on patients with absolute neutrophil counts below 1000/mm3, due to decreased sensitivity. Despite these limitations, CMV antigenemia testing is still considered a viable choice for diagnosing and monitoring CMV infection, especially when viral load testing is not available.
Quantitative real-team polymerase chain reaction (PCR) is the most commonly used method to monitor patients at risk for CMV disease and response to therapy, as well as for diagnosing active CMV infection. The advantages of using a quantitative PCR assay include increased sensitivity over antigenemia testing, quick turnaround time, flexibility of using whole blood or plasma specimens for up to 3-4 days at room temperature, and the availability of an international reference standard published by the World Health Organization (WHO).
Several assays from Roche, Abbott, and Qiagen are available and FDA-approved. The targets of these assays vary, with some targeting polymerase and other targeting CMV major immediate early gene. These assays are all calibrated with the WHO international standard, which was developed in 2010 to help standardize viral load values among different labs when results are reported in international units/mL. The goal of this international standard is to decrease the interlaboratory variability of viral load, and determine the appropriate cut-offs for determining clinical CMV disease. There is still improvement to be made in this area, as variability still exists between labs.
There are several tests to determine the CMV status of patients. Some of these tests are suited for particular goals, such as serology for determining serostatus prior to organ transplantation, or histology and IHC to diagnose tissue-specific CMV disease. For diagnosis and monitoring of general CMV disease, the test of choice in most laboratories is quantitative PCR, which offers automated, quick and sensitive results. Antigenemia, while dated and labor intensive, is still an acceptable alternative when PCR is neither available nor cost-effective for smaller labs. Both of these testing methods are preferred over viral culture, which has poorer diagnostic sensitivity and relatively longer turnaround time.
Despite the numerous advantages quantitative PCR has, there is still variability in viral load counts among laboratories. This is due to varying DNA extraction techniques, gene targets used by PCR, and specimen types used. There is still a lot of work to be done in standardizing testing in regards to not just CMV, but also other viral pathogens like Epstein-Barr virus, BK virus, adenovirus and HHV6. Updated standards and increased use of standardized assays will hopefully decrease this variability between labs to improve testing results and in turn, improve patient care.
Kotton CN, Kumar D, Caliendo AM, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2013;96(4):333-60.
Hayden RT, Sun Y, Tang L, et al. Progress in Quantitative Viral Load Testing: Variability and Impact of the WHO Quantitative International Standards. J Clin Microbiol. 2017;55(2):423-430.
Kotton CN, Kumar D, Caliendo AM, et al. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018;102(6):900-931.
-David Joseph, MD is a 2nd year anatomic and clinical pathology resident at Houston Methodist Hospital in Houston, TX. He is planning on pursuing a fellowship in forensic pathology after completing residency. His interests outside of work include photography, playing bass guitar and video games, making (and eating) homemade ice cream, and biking.
Three months ago, life in the laboratories in these United States carried on as usual, and no one could probably have predicted where we stand today. The COVID-19 pandemic has changed the way laboratorians work everywhere. Some staff have had hours cut because of decreased workloads, other labs worked around the clock to bring new testing on board, and others dealt with staffing shortages due to illness. It has been a wild ride, and through it all, a great many safety issues have arisen. Common lab practices are now viewed through a new lens- is it acceptable to bring hematology slides for review into a clean pathologist’s office? Can we wear surgical masks worn in the lab into the break room? There are many good questions, but some of the answers can be found using references offered from reliable sources. Not everything you read online can be believed, but here are some references that may be necessary and that provide important information.
The pandemic has created a world-wide shortage of PPE, and some have wondered what can be done as resources diminish. The CDC has some good information about calculating how long PPE can be used and how long it can last. There are good guidelines about re-use and extended use of PPE.
The CDC also offers laboratories a set of COVID-19 guidelines for performing testing, biosafety issues, waste management, and protection against aerosols. These guidelines are thorough, and they can be very helpful should safety challenges arise.
Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19):
Many of these references are updated regularly, so be sure you go to go to the source when making safety policy about COVID-19 tasks.
Laboratorians are now literally on the front lines during this novel coronavirus pandemic. While many public and commercial services have been scaled back, restaurants are closing, and many people are staying or working at home, lab staff are doing their level best to keep coming to work despite the extremely unusual circumstances and hardships.
I am here to serve as well. If you have questions about how to safely navigate this national (and global) emergency while working in the lab, ask me (firstname.lastname@example.org). I will do my best to provide any lab safety resources you may need. Make sure the decisions you make during these days are safe, sound, and based on the most recent resources available to you.
–Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.
Much has changed quickly with SARS-CoV-2 virus (COVID-19) testing. Several commercial options are now available. Labs have less problems getting control material (positive samples are no longer in short supply). And labs that opted to bring on testing are now running multiple versions of COVID-19 molecular tests with a combination of high speed platforms or high throughput. Rapid cartridge tests are used for clearing people from the ED/ removing contact isolation on inpatients while the high throughput assays are used for routine screening.
However, several bottlenecks still exist. There are shortages of nucleic acid extraction kits, collection swabs and viral transport media. Fortunately, some recent studies have demonstrated preliminary evidence for using alternative sample types, collection methods, and storage conditions.
One of the first tenets of molecular diagnostics is isolation and purification of nucleic acid. Therefore, it was surprising to see a report on an extraction-free COVID-19 protocol from Vermont (Bruce EA et al.). This study initially analyzed two patient samples and showed drops in sensitivity of ~4Ct cycles. While this would not be suitable for low level detection, many viral samples have high levels of virus that still would permit detection. The team went on to test this method on 150 positive specimens from the University of Washington and found 92% sensitivity with 35% sensitivity at the low viral load range (Ct value> 30). This was improved with a brief heat inactivation step (Table 1). This was similarly seen in a study from Denmark, where brief heat inactivation of extraction-free methods (Direct) had 97% specificity in 87 specimens (Table 2).
Some similar studies out of Chile also showed extraction-free protocols on a larger number of specimens, and they reported a loss in sensitivity varying from 1-7 Ct cycles depending on the primers used.
As this novel Coronavirus has an RNA-based genome, RNA is the target of molecular tests. As RNA is susceptible to degradation, there have been concerns over sample storage. Should it be refrigerated? Frozen? How do multiple freeze-thaw cycles impact specimen stability? Are there viable alternatives to viral transport media? One preliminary study explored these questions very nicely. They took X multiple sample types (NP, BAL, saline storage media) and stored them at 20C, 4C, -20, and -70 for multiple days up to 1 week and then analyzed the level of virus detected. In each case, the loss in sensitivity was minimal (<2 Ct cycles from day 0 to day 7) at room temperature with comparable results at lower temperatures (Table 3).
Lastly, alternative sample types such as saliva will help break the bottleneck in swabs and viral transport media. I was surprised to hear about this being a suitable alternative. Having worked with saliva for DNA analysis, I know it can be contaminated, of variable quantity, includes digestive enzymes and is viscous (slimy). These are not characteristics a lab would look for in a specimen type being used for high-throughput testing where several sample failures could occur. But these researchers from Yale showed measurable levels of SARS-CoV-2 that facilitated even higher sensitivity than nasopharyngeal swabs (Wylie AL et al).
With a much-needed increase in testing for this country, optimizations need to be implemented to improve efficiency. These steps alone will not be enough, but if we can have extraction-free testing of saliva collected at home, this would provide a substantial benefit to bringing easy testing to everyone.
-Jeff SoRelle, MD is a Chief Resident of Pathology at the University of Texas Southwestern Medical Center in Dallas, TX. His clinical research interests include understanding how the lab intersects with transgender healthcare and improving genetic variant interpretation.
An elderly woman with a past medical history significant for end-stage renal disease status post deceased donor kidney transplant in 2018 (on immunosuppression), type 2 diabetes mellitus, and recurrent urinary tract infections presented to nephrology clinic with right ear pain and rash of three weeks. She was otherwise in her usual state of health. On physical exam, there were exophytic itchy papules with hemorrhagic crust and ulcerations on the ear (Image 1) and arm. A few of these papules showed central umbilication (Image 2). Erosions were also present on the upper back, face, neck, and forearms. Patient was referred to dermatology with concern for disseminated infection versus neoplasia. Complete blood count showed mildly elevated white cells. Serologies, cultures, imaging, lumbar puncture, and biopsy were performed.
Blood studies revealed a Cryptococcus antigen titer of 1:4096 along with a CSF antigen titer of 1:2048. Additionally, the CSF gram stain demonstrated yeast and cultures grew Cryptococcus neoformans. Opening pressure was normal and protein was slightly elevated to 53 mg/mL with 36 nucleated cells with a differential including 64% lymphocytes. Biopsy culture of the left cheek was positive for C. neoformans and a left forearm biopsy showed nodular aggregates of encapsulated yeasts, surrounded by relatively sparse lymphohistiocytic inflammation (Images 3-4). A CT of the chest showed innumerable pulmonary nodules concerning for infection.
Cryptococcus is an encapsulated basidiomycetous fungus typically found in soil and pigeon droppings.1 Two species comprise the majority of Cryptococcus infections: C. neoformans and C. gatti. C. neoformans is most commonly seen in immunosuppressed patients, particularly in the setting of AIDS.2C. gatti infections may be seen in more immunocompetent patients and appears to be more geographically restricted to the tropics and Pacific Northwest.3C. neoformans infections can present as lung disease associated with symptoms of fever, shortness of breath, or cough and characteristically may spread to the central nervous system to cause meningitis.4 Lumbar puncture may show significantly elevated opening pressures.5 Other features of disseminated Cryptococcus infections include rash, endocarditis, ocular lesions, or multiorgan failure.6
This case is a somewhat unusual presentation of disseminated Cryptococcus infection characterized only by skin findings without clinical features of pulmonary or CNS infection. Approximately 15% of patients with disseminated infection may show cutaneous findings but primary cutaneous cryptococcosis is rare.7 Cryptococcal skin findings are quite varied, but may present similar to molluscum contagiosum, as dome shaped papules with central umbilication.7,8 On microscopy, small variably sized round yeasts without hyphae are characteristic. These yeasts may show a clear or pale staining halo representing the capsule and are highlighted well on Grocott’s Methenamine Silver or Periodic Acid-Schiff stains. Histology may demonstrate innumerable extracellular yeasts accompanied by foamy stroma and minimal inflammation or more granulomatous tissue reaction with necrosis, ulceration, and mixed inflammation. In conclusion, disseminated Cryptococcus must be considered in the context of new skin findings in an immunocompromised patient even if typical pulmonary or CNS findings are not identified.
Bratton EW, El Husseini N, Chastain CA, Lee MS, Poole C, Sturmer T, et al. Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant. PloS One. 2012;7(8):e43582
MacDougall L, Fyfe M, Romney M, Starr M, Galanis E. Risk factors for Cryptococcus gattii infection, British Columbia, Canada. Emerg Infect Dis. 2011 Feb;17(2):193-9.
Sabiiti W, May RC. Mechanisms of infection by the human fungal pathogen Cryptococcus neoformans. Future microbiol. 2012 Nov;7(11):1297-313.
Abassi M, Boulware DR, Rhein J. Cryptococcal Meningitis: Diagnosis and Management Update. Curr Trop Med Rep. 2015;2(2):90–99. doi:10.1007/s40475-015-0046-y
Clark RA, Greer D, Atkinson W, Valainis GT, Hyslop N. Spectrum of Cryptococcus neoformans infection in 68 patients infected with human immunodeficiency virus. Rev Infect Dis. 1990 Sep-Oct;12(5):768-77.
Srivastava GN, Tilak R, Yadav J, Bansal M. Cutaneous Cryptococcus: marker for disseminated infection. BMJ Case Rep. 2015;2015:bcr2015210898. Published 2015 Jul 21. doi:10.1136/bcr-2015-210898
Akram SM, Koirala J. Cutaneous Cryptococcus (Cryptococcosis) [Updated 2019 Aug 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448148/
-Dr. Stanton Miller is a second year AP/CP resident at UT Southwestern Medical Center who is interested in Dermatopathology.
-Dr. IJ Frame is a board-certified Clinical Pathologist who is completing his Medical Microbiology fellowship at UT Southwestern Medical Center.
-Dr. Dominick Cavuoti is a professor of AP and CP at UT Southwestern, specializing in infectious disease pathology, cytology and medical microbiology.
-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. She has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.
With recent criticisms in the media, both foreign and domestic, on the United States’ response to COVID19 as well as accusations and summary conclusions that the United States is not a global health power house nor is it as prepared to handle COVID19 as nations around the world that are plagued by infectious challenges daily, it is important to revisit history of recent pandemics and the prior US responses to them to put the current interpretations of “failing” into perspective.
In 2003, the SARS epidemic began in China with the first possible case documented in November 2002. At the time, US relations with China were such that CDC field offices and CDC field officers, including permanent deploys and temporary lead deploys from central CDC in Atlanta, GA, were available to assist the Chinese healthcare system and government with the response to SARS. Through this effort, statements from CDC field directors such as, “This town is going to have a spike and we need 300 more beds,” was answered by the Chinese with a new hospital being built with 300 beds in less than 3 days. Such transparency, collaboration, and communication were possible at the time but relationships have diminished in recent years. During the SARS outbreak, there were 8,098 patients infected (known by positive testing) and 774 deaths (9.5%) which affected 26 countries including the US; however, the US only had 8 to 27 cases (depending on source) and no deaths. Although the first cases traced back to late 2002, the disease was not sequenced and declared until April 2003, but testing was available shortly thereafter. Control measures locally and globally with some help from testing stifled the pandemic in a matter of weeks and the threat was near zero by the end of 2003. No resurgence has occurred. From this outbreak, the US and the world learned how to deal with novel coronaviruses and how to coordinate and collaborate for future potential outbreaks. Such lessons include the need for transparent communication and direct in country collaboration, rapid move to testing distribution, and high-level knowledge of pandemics and who nations should respond.
In 2009, the H1N1 pandemic began. The CDC activated its emergency system within 7 days of the first case, the US and the WHO declared the pandemic within 9 days of the first case, and testing was available within 14 days of the first case. The US had 60.8 million cases (confirmed positive tests) with 274,000 hospitalizations (0.5%) and 12,469 deaths (4.5% of hospitalizations, 0.02% of cases). The incidence from the disease was due to the rapid respiratory spread very similar to routine influenza but on top of a system (including hospital processes and national approaches to testing with integrated public health laboratory systems) that was prepared and able to nimbly adapt. In this case the rapid advent of testing was crucial to controlling case, getting patients on treatment, and tracking the disease. H1N1 was then subsequently included in the annual influenza vaccines.
From 2012-2014, the MERS-CoV virus, originating from and primarily endemic in the Arabian Peninsula, was a challenge for global heatlh because of the high mortality rate (30 to 40%) and the very efficient spread of the virus. All cases arising outside of the Arabian Peninsula were traced to travelers from that region. The first known cases were in April 2012 with the first recognition of the virus causing the disease in September 2012. The CDC developed a test for MERS in 2012 and subsequently an EUA from FDA was granted on June 5, 2013. The first positive cases of MERS in the US occurred in May 2014, almost 1 year after testing had been available. To date, only 2 confirmed cases of MERS have been diagnosed in the US which were traveling healthcare workers who had treated patients in Saudi Arabia.
The Ebola epidemic in West Africa from 2014-2016 had a total global case count of 27,000+ with 11,000+ deaths (46% mortality). However, in the US only 4 patients were ever diagnosed with EBOLA and 11 patients were treated for EBOLA with only 2 total deaths (18% mortality). Why was the case count so low for the US and why was the mortality nearly a 1/3rd of the overall epidemic? Immediate response from the US government to control incoming patients (the only transmission inside the US was from patients who were travelers to healthcare workers) and availability of testing prior to the outbreak (with the CDC). Nigeria was able to diagnose the first case in Lagos (a traveler from Liberia) because a scientist in Nigeria had developed a rapid EBOLA PCR six months before the outbreak occurred. Nigeria only had 8 deaths from 20 confirmed infections (40% mortality). Why did Nigeria get ahead of the game? Immediate response from government and availability of testing. The unfortunate results in Liberia, Sierra Leone, and Guinea were less about lack of response and lack of testing and mostly due to poor infrastructure for health.
The current pandemic of COVID19 started on November 17th (earliest confirmed case in China) and was a reported disease cluster from China to WHO by December 31st, 2019. The first case in the US was documented to have occurred on January 19, 2020. The FDA, in response to information from central administration and pressure from multiple entities, allowed testing for COVID19 through Emergency Use Authorization (EUA) on February 28, 2020 (more than one month after the first US case). As of April 28, 2020, the US has had 1,026,771 confirmed cases (positive testing) and 58,269 deaths (5.7% mortality) affecting all 50 states in the setting of an unprepared system (i.e., insufficient testing, insufficient pandemic planning at the national level, insufficient in country data from source countries). Data has shown in the laboratory that the SARS-CoV-2 virus shares 74 to 90% genetic homology with the original SARS virus but has a 10-fold increased affinity for binding which suggests that its natural biological virulence could be 10x that of SARS. If proper systems, testing, and planning had been in place, we can conservatively estimate that there would currently be 102,667 confirmed cases in the US and 5,827 deaths. These excess cases and excess death are, therefore, a direct result of the lack of systems, testing, and planning (52,442 excess deaths of US citizens).
There are conspiracy theorists that argue SARS-CoV-2 was created or modified from a different virus by human manipulation with a most recent endorsement of HIV Nobel Prize Laureate Luc Montagnier—statements that were almost immediately refuted by other prominent scientists. If there was a credible threat from SARS-CoV-2 when the sequence was released, that would have been an even more convincing argument that preparation was needed. But the threat of SARS-CoV-2 from just the observed medical cases and initial reports should have warranted a brisk and complete response from leadership. That such responses were delayed because of a multitude of failed responses (pandemic planning, testing, situational awareness, field deployments, etc.) can be argued from now until the next pandemic occurs. But our collective prior experience with pandemics (4 of them in 2 decades) provided plenty of evidence and case-studies for how we should have responded.
ASCP along with other organizations reached out to our membership and the community for support of a call for a National Testing Strategy resulting in tens of thousands of letters to elected representatives and a subsequent plan for a National Testing Strategy released by the US government. The CARES Act released this week includes billions for testing.
These efforts are for our membership who are the medical laboratory professionals working 12 hours shifts to provide the testing needed by their patient populations.
These efforts are for our pathologist members who are informing and controlling hospital and government responses around testing through their rapid decisions and their expertise.
These efforts are for our pathologist’s assistance at all levels who keep anatomic pathology running with our pathology trainees despite massive volume challenges.
These efforts are for our PhD members whose expertise in science, design, and evidence acquisition is rapidly leading to new testing and eventually new vaccines.
These efforts are, most importantly, for our patients, the center of all that we do, to ensure that they have access to testing and the peace of mind they need to move forward from this pandemic.
-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.
The patient is a 53 year old male with a past medical history of chronic obstructive pulmonary disease, who presented to the emergency department with one day of right calf pain, worse with weight-bearing, with radiating paresthesias, and a pale, cold right foot. He also endorsed a history of intermittent fatigue and knee pain. The patient works on farm and has an 82 pack year smoking history. He was diagnosed with a right popliteal artery occlusion and started on IV heparin. A transthoracic echocardiogram revealed an aortic valve mass.
Five days after admission he underwent a thromboembolectomy of the occluded vessel. A further six days later he underwent a procedure to excise the aortic valve mass, but ended up having an aortic valve replacement. Cardiothoracic surgery described a friable mass with a large base, consistent with a vegetation that might be seen in infective endocarditis, and sent the mass for surgical pathology and aerobic and anaerobic cultures. He was started on empiric vancomycin by infectious disease.
The patient denied recent fevers, chills, sweats, weight loss or changes in appetite, cough, chest pain, abdominal pain, nausea, vomiting, diarrhea, constipation, painful urination, rash, or unusual bone or joint pain. Doxycycline and rifampin were added for further coverage.
Blood cultures drawn on admission showed no growth at 5 days. Initial gram stain of tissue from the mass showed many gram positive beaded rods. Anaerobic cultures of this tissue grew a single colony of Micrococcus and a single colony of a gram positive bacilli, which also grew aerobically and was identified by Mayo as Corynebacterium spp., not jeikeium. Serology for Bartonella was negative. Q fever serology showed elevated titers of phase I Ab IgG only.
Surgical pathology of the aortic valve mass is shown below:
GMS, B&B, AFB, and Fite staining were negative for definitive organisms.
A second set of blood cultures showed no growth and 5 days, and AFB cultures were negative, and second Q fever serology showed a decrease in the titer of phase I Ab IgG.
A PCR of residual heart valve tissue identified Tropheryma whipplei.
The diagnosis of Tropheryma whipplei is made by T whipplei PCR, PAS stain, or T whipplei immunohistochemical staining.1 As these are all non-routine tests for a microbiology work-up, the diagnosis depends on high clinical suspicion.
Most often seen in the gut, T whipplei infection classically manifests as arthralgias, abdominal pain, weight loss, and diarrhea.2 However, it is also a rare source of culture-negative endocarditis, as seen in the case above.
The organism is a gram positive bacillus that is common in the environment and found in the saliva of up to 35% of healthy hosts.3 Furthermore, IgG antibodies to T whipplei have been detected in the blood of up to 70% of healthy individuals.4 Microscopically, there is minimal inflammatory response to this organism. Because of this and the classic symptoms, the characteristic foamy macrophages were initially thought to be indicative of a metabolic disorder.5 Once discovered and studied, it was found to most commonly affect males of European descent, which with the minimal inflammatory response to the organism led to the postulation that this population may have a heritable immunodeficiency.6 Others have suggested that the organism itself may have a role in down-regulating the immune response.7 A variety of immunologic disturbances have been associated with the disease, including down-regulation/absence of MHC II molecules and general dysfunction of monocytes/macrophages.1,7,8
Treatment varies by extent of disease, but it generally includes ceftriaxone or penicillin G followed by an extended course of TMP-SMX.1
In the case of our patient, he demonstrated symptomatic improvement after aortic valve repair followed by four weeks of ceftriaxone, with a plan to transition to TMP-SMX for one year.
Durand DV, Lecomte C, Cathébras P. “Whipple disease. Clinical review of 52 cases.” Medicine (Baltimore). 1997;76(3):170.
Street S, Donoghue HD, Neild GH. “Tropheryma whippelii DNA in saliva of healthy people.” Lancet. 1999;354(9185):1178.
Raoult D, Birg ML, La Scola B, et al. “Cultivation of the bacillus of Whipple’s disease.” N Engl J Med. 2000;342(9):620.
Whipple GH. “A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues.” Bull. Johns Hopkins Hosp. 1907; 18:382–391.
Fenollar F, Puéchal X, Raoult D. “Whipple’s Disease.” N Engl J Med. 2007;356(1):55.
Ectors NL, Geboes KJ, De Vos RM, et al. “Whipple’s disease: a histological, immunocytochemical, and electron microscopic study of the small intestinal epithelium.” J Pathol. 1994;172(1):73.
Moos V, Schmidt C, Geelhaar A, et al. “Impaired immune functions of monocytes and macrophages in Whipple’s disease.” Gastroenterology. 2010;138(1):210.
-Frederick Eyerer, MD is a 2nd year anatomic and clinical pathology resident at the University of Vermont Medical Center.
-Thomas Koster, DO is a 1st year anatomic and clinical pathology resident at the University of Vermont Medical Center.
-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.
Before I became an MLS Program Director, I worked for nearly 20 years in Hematology. I was particularly interested in Coagulation and was excited to work as the Coordinator of the Special Hematology lab, overseeing coagulation and special RBC testing. Our Pathology Department offered a consultation service for these cases and I was included along with a team of pathologists, residents, fellows, and clinicians that worked with patients and their families to diagnose patients and manage their treatment plans.
One of my most memorable moments was when we had a patient with a previously diagnosed platelet disorder who became pregnant and sought advice regarding the delivery of her child. Her doctors worked with our pathologists to weigh the risk of bleeding complications associated with different modes of delivery, while also considering the welfare of the child who may have inherited the platelet disorder. It was decided that they would take a non-surgical approach to minimize risk for the mother, but would monitor the baby closely. That’s where I came in! I was asked to be on call for the child’s delivery in order to be available to collect samples to monitor the baby’s progress and perform the necessary testing to inform her doctor’s decisions. At the time, on-call meant carrying a pager. When my pager went off, I met the obstetrical team at the hospital and accompanied them into the delivery suite. Labor progressed as expected and when the baby’s head was visible, I assisted the doctor in collecting a tiny amount of blood from the baby’s head, enough to look quickly under a microscope to determine if the baby’s platelets showed any similarity to the mom’s. I was delighted to say that the platelets appeared normal in number and size, minimizing the bleeding risk for the baby. The patient continued to deliver a healthy baby girl without complications.
Once the delivery was complete, I was able to collect enough blood from the placenta to perform definitive testing to rule out any evidence of the platelet disorder in the baby. This was an opportune time as the testing required a large volume which would have been difficult to collect from an infant. Once again, the testing ruled out any evidence of the bleeding disorder in the baby. Mom not only had a beautiful baby, but enjoyed the peace of mind associated with the results of her laboratory testing. As was often the case with our patients, we would see them from time to time in the management of their bleeding disorder. It was always a joy to see our patient visit with her daughter.
-Susan Graham, MS, MT(ASCP)SHCM is the Chair and MLS Program Director in the Department of Clinical Laboratory Science at SUNY Upstate Medical University. Ms. Graham is a current volunteer for ASCP, serving on the BOC Board of Governors, the Hematology and Joint Generalist Exam Committees and the Patient Champions Board.
Although you better not have gone too far since last time, self-isolation and social distancing are still critical for us to get through this. Wash those hands, and dust off books and board games. #StrongerTogether (apart), am I right?
Yes, it’s going to be another piece on the current pandemic. It probably will continue to be so until conditions change. So, as your contributor to virology and testing these last two months, I’d like to take a minute to “zoom out” a bit and look at this pandemic in a different way.
It’s highlighting lots of things in healthcare from supply chain, to political regulatory red tape, to the mechanism of deliverables in the United States. And despite the title, I have no romantic epilogues about anything happening in Columbia at the turn of the 20th century. However, very much like the original book’s protagonist, I’d say there are a lot of us in Pathology and Laboratory Medicine alike who are champions of the scientific cause for advancement, education, and positive outcomes. And what better, more fitting of a time to celebrate this cause, than Laboratory Professionals Week 2020!
*** Never forget how vital you all are at every level. Technicians, technologists, medical laboratory scientists, administrators, directors, managers, residents, fellows, faculty, and staff all fit together in a magnificent (but often too unseen) tapestry that makes every patients’ tests results mean something so much more than numbers on a printed report. You’re all lab heroes, we’re all lab heroes. Go make sure you thank some of them this week (or anytime) and a heartfelt thank you to all of you from me as well! ***
In the mere month since I last wrote a piece for Lablogatory, so much has changed with the pandemic as well as my role in local and academic public health efforts. To name a few, I trained with the New York City Medical Reserve Corps as a public health educator early during the pandemic, I was invited to give a lecture on SARS-CoV-2 and COVID-19 testing considerations for lab professionals by the excellent pathologists who run the PathCast series, and I just recently finished a two-day series with an organization called Proceed who are sponsored by the National Center for Training, Support, and Technical Assistance (NCTSTA)—a CDC grant-funded education web series. I’ll mention a little bit about all these things (and of course link you to the material) and talk about how it all fits into what has quickly become a complicated social pandemic response.
Almost as soon as I set up shop to start my medical school clerkships and clinical training in New York City, I joined the New York City Medical Reserve Corps—a collection of volunteer healthcare first responders in the event that the city at large ever needed to mobilize every available healthcare personnel during a disaster or health emergency. *Spoilers: turn on the news* At the same time I was prepping some pre-clinical research in infectious disease healthcare and contributing to ASCP’s Choosing Wisely initiatives addressing Hepatitis C testing in vulnerable communities with some of the nation’s highest rates of infection (read the flashback primers I wrote here and here), I was attending NYC-MRC seminars and becoming a nationally certified disaster responder. There have been drills, seminars, and lectures since joining in 2018 but nothing to really contribute to while I moved through clinicals. Welp, clinicals ended, I had a few weeks off for residency interviews, then Kung Pow! Enter the defining viral pandemic of 2020! Smooth sailing lectures became phone network scrambles to see if I obtained my medical license yet since New York’s hospitals were slammed! The last meeting I remember going to was a training on disseminating appropriate information to various levels of practice/professions. I didn’t know it yet, but this became paramount knowledge for me.
What Information Matters Most?
So what exactly did I learn? Essentially, it’s nothing groundbreaking or new, but the way you address certain topics matters more than you might realize. I once found myself in a room of mixed level healthcare providers, homeless shelter staff, local public health officials, hospital nurses, and lay people—that’s a broad range of knowledge and practice exposure. If you talk about upregulated ACE-2 receptor expression in intra-viral inflammatory response before full blown ARDS and DAD visible in lung biopsies you’ve lost half the crowd; and if you talk about epidemiology basics like reproductive number (R0), first cases found (FFX), and trace tracking, your provider audience is suddenly looking at their phones. But almost none of them know enough about laboratory testing, regulations, or quality assurance measures—so that became my target, and my bridge to connect everyone. I began collaborating with a friend and colleague Dr. Emeka Ajufo, who matched into his top-choice pain management and rehabilitation (PM&R) residency, and started creating content that connected topics like wellness, one health, and prevention while at the same time understanding deliverables and quality behind lab testing.
So this partnership content got noticed on Twitter (@CEKanakisMD) by the folks that run the PathCast simulcast series on Facebook and YouTube. Dr. Rifat Mannan (@mannanrifat03 on Twitter) from the University of Pennsylvania Hospital and Dr. Emilio Madrigal (@EMadrigalDO on Twitter) from Massachusetts General Hospital have been hosting and promoting a mountain of impressive faculty lectures for all kinds of topics in pathology since 2016. They host them live for viewing across an international audience, take questions, and save each video for future viewers. Their wide and comprehensive hour-a-piece lecture series is enjoyed my many and offers a free, no-hassle viewing experience. I was honored enough to be considered to give a talk on their channel, and after discussing more details with them, it appeared that there was a unique opportunity for some high-value topical information on laboratory and quality testing during this COVID-19 pandemic. If you haven’t heard of this series, you’re missing out. Please go like and subscribe to both their Facebook and YouTube platforms ASAP—you won’t be disappointed!
What’s a Good Test in a Pandemic?
Excellent question! You’ve probably already heard me talk about this before… This specific question came from discussions on social media with friend, colleague, and fellow ASCP Social Media Committee member Dr. Rodney Rhode (@RodneyRohde on Twitter). If I make it sound like I’ve been busy these last months, Dr. Rhode operates at another level: he’s publishing articles on the pandemic, running laboratory operations, is a research dean and department chair at Texas State, and is disseminating clinical information faster than I could even process it—he’s one of many pathology rockstars in our field! When we spoke before the PathCast series, we talked a bit about the problems in FDA fast-track clearance of all these new tests that would barely make the cut during non-pandemic “peace time.” The Emergency Use Authorization program allows the FDA to push forth tests available for commercial distribution with around 30 or so specimen validations that often don’t break the 60-70% sensitivity/specificity ceiling—yeah, I know. But it’s the best we’ve got and hospitals all over the country are working as hard as they can to bolster their validation studies with more specimens, better controls, modified protocols, and enhanced LDTs (laboratory developed tests) just to meet demand.
There are not enough tests, but there are also too many tests. Just before that PathCast lecture went live, I got an email from our awesome Lablogatory manager and editor, Kelly Swails (@kellyswails on Twitter) about some generic antibody testing kit that people were going nuts over. The problem was on page 6 of the manufacturers’ insert: “this test has not been reviewed or cleared by the FDA.” Well, there’s a problem—and they’re a dime a dozen. Since then, friends, colleagues, and all kinds of inquiries have come my way to ask, “is this a good test?” as people find kits available for purchase… it’s been a mess to say the least. But we laboratorians know: one of our core principles isn’t to let quantity overrule quality, especially when it comes to patient testing. That’s a non-starter.
Shortly after the PathCast buzz started to settle, one of my MLS grad school classmates who now works with a local public health education and training organization in New Jersey, reached out to see if I could expand the discussion on testing to include problems with access and issues with vulnerable populations. Check and check. Go back and look at some of my posts on Zika and arbovirus work in the Caribbean and you just know I was excited to help! Proceed, Inc. has been a supportive community leader in addressing health and accessibility concerns in their local region and reaching out to form partnerships under the banner of the National Center for Training, Support, and Technical Assistance program (supported by the Centers for Disease Control and Prevention (CDC), Office of Minority Health (OMH), Administration for Children & Families (ACF), and other local entities.)
If you watch the news it’s individuals over 65 years of age and/or anyone with a significant related underlying condition: asthma, COPD, hypertension, etc. And, while that’s true, that’s just the tip of the vulnerability iceberg. Let’s remind ourselves for a minute about the inward and outward concepts of “social determinants of health.” When we want to label a population as vulnerable, or better put, increasingly susceptible to the negative effects of their living conditions in the setting of health care access, we have to think about all the things that contribute to a person’s health: their relationships, their stable/unstable living conditions, level of education, their income/expense ratio, possible language barriers, race/creed/color, disability, addiction, those experiencing homelessness, and concerns for their individual safety to name just a few! Inwardly, should we choose to engage these vulnerable communities we must do so with proper inclusion and a foundation of trust, communication, clarity of purpose, partnership, support, and—arguably most importantly—cultural humility. I also offered the attendees two resources as handouts which are available to you if you attend the recorded webinar as well: one COVID-19 safety factsheet directly from the CDC, and an adaptation of social determinants inventory I designed when my arbovirus team worked on Zika education in Sint Maarten. In truth, we’re all vulnerable in different ways, but when we work together to address gaps in delivery and access we end up #StrongerTogether—and that’s something our laboratory community knows a thing or two about!
The Tipping Point
The $64,000 two-part question: are things getting better or worse, and when will things go back to normal? My 64¢ answer: we don’t really know yet because there’s not enough active current data. The best estimates have case-peaks in places like Manhattan reaching a sort-of plateau as non-emergent hospitalizations, intubations, and COVID-19 cases slow down—but don’t mistake that for a full-on stop. Social distancing and quarantine initiatives in places like New York, Chicago, and other cities are the most effective NPI (non-pharmaceutical intervention) we’ve got. And that’s saying a lot. We have data that suggests previous pandemics had second waves as soldiers came back from war during the 1918 Flu pandemic in the states, so we’ve got to be careful and mindful of what we’re up against. But it’s getting easier and easier to become listless and bored of Netflix and stress-baking. People are getting legitimate cabin fever, although I’d rather we all had that than another, more topical viral illness these days. We’ve got a ways to go with all our frontline work, our NPI distancing, and stratified testing/tracking measures and we have to keep at it, otherwise we’ll undo all the progress we’ve made. And, that “new” vulnerable population, with motivations most certainly rooted in fear and stress, demanding to “reopen” the country since COVID is, after all, a hoax: don’t underestimate their power to tip the scales and send us back. The marriage of policy and politics is a patchy one at best, but efforts from professional advocacy societies like the ASCP are making strides, pushing both at the local and federal levels to demand active and appropriate responses to address proper COVID testing. But things don’t have to be so contentious.
Fear and Loathing vs. Love in the Time of COVID?
So where does this leave us now? You’ve listened to my litany of testing complexities and considerations for preserving quality of healthcare delivery to all types of patients and you know where I stand on having a passion for preserving the importance and integrity of our professional role as leaders in this field. Do we give in to frustration or keep fighting this pandemic in more, creative ways? The answer, to me, is obvious. We move forward, as always. But most especially, this lab week should be something different because it not only highlights our work as traditionally “behind the scene,” but underscores our critical importance to the delicate house of cards balanced between clinical healthcare, decision making, public health, and public opinion. It’s not only our job to make sure the tests are good (even during pandemics) but that we represent a consistent and reliable message of evidence-based truth for patients and clinicians to rely on—like we always do.
Happy Lab Week 2020. Stay safe, wash your hands, and remember social distancing doesn’t just mean staying at home. It also means integrating compassion into a new routine, and caring for neighbors, colleagues, and friends in new profound ways.
See you all next time!
-Constantine E. Kanakis MD, MSc, MLS (ASCP)CM is a new first year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. His posts focus on the broader issues important to the practice of clinical laboratory medicine and their applications to global/public health, outreach/education, and advancing medical science. He is actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Watch his TEDx talk entitled “Unrecognizable Medicine” and follow him on Twitter @CEKanakisMD.