COVID19 and the Lessons We Learned from Prior Pandemics

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.

References

  1. https://www.webmd.com/lung/news/20030411/sars-timeline-of-outbreak#1
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904415/
  3. https://en.wikipedia.org/wiki/2002%E2%80%932004_SARS_outbreak
  4. https://www.fda.gov/media/72313/download
  5. https://www.who.int/csr/sars/testing2003_04_18/en/
  6. https://www.cdc.gov/about/history/sars/timeline.htm
  7. https://www.cdc.gov/flu/pandemic-resources/2009-pandemic-timeline.html
  8. https://www.cdc.gov/flu/pandemic-resources/2009-h1n1-pandemic.html
  9. https://www.cdc.gov/coronavirus/mers/about/index.html
  10. https://www.cdc.gov/about/ebola/timeline.html
  11. https://en.wikipedia.org/wiki/Western_African_Ebola_virus_epidemic
  12. https://www.scmp.com/news/china/society/article/3074991/coronavirus-chinas-first-confirmed-covid-19-case-traced-back
  13. https://www.who.int/news-room/detail/27-04-2020-who-timeline—covid-19 https://www.nature.com/articles/s41467-020-15562-9
  14. https://www.worldometers.info/coronavirus/country/us/
  15. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
  16. https://en.wikipedia.org/wiki/COVID-19_testing
  17. http://www.xinhuanet.com/english/2020-04/21/c_138995464.htm
milner-small

-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.

Love in the Time of COVID-19

Hi everybody—welcome back!

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.

NYC-MRC

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.

Image 1. Throw back from my Instagram (@CEKanakisMD) and one of my first sessions on training to become a disaster responder for the NYC-MRC.
Image 2. The last meeting I attended, and probably the last meeting I’ll have attended while living in Manhattan. Learning some tools, tips, and tricks on effective communication during uncertain times proved invaluable for what was to come. (also from my Instagram @CEKanakisMD)

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.

Image 3. We’re still in editing and sound production, but we’ve worked together before on podcasts and other content I’ve featured in previous blog posts, like this one! Check out more of Dr. Ajufo’s PM&R work here. (We may or may not be discussing the finer points of adequate nasopharyngeal swab technique here…)

PathCast

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!

Image 4. Here’s the title card for my lecture on SARS-CoV-2 and COVID-19 testing considerations for laboratorians. It aired on Friday, April 10th at 8:00 ET and I’m proud to say that it received almost 20,000 individual views from just under 100 countries around the globe. Talk about global pandemic attention and response timing! Got an hour? Check it out here.

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.

Image 5a. Here’s an updated slide from the PathCast talk. The current situation report: 43 commercially available kits, pumped out daily like an overworked approval factory, some are better than others. We’re focused more on molecular/PCR/NAAT for now for its clinical and diagnostic utility. Antibodies will become useful when we discuss “post peak curve” solutions like tracking, vaccines, and therapies like convalescent plasma. What makes a good test in a pandemic? Good laboratory practices.
Image 5b. This is the rapid serology kit that is commercially available but not FDA reviewed, at all. Courtesy of Kelly Swails. I’m not here to name or shame, but this is just one of hundreds of these tests out there. And it’s a definite challenge when those of us in Laboratory Medicine are not part of the process. So caveat emptor/buyer beware—don’t let your lab’s precious time or resources go into snake oils.

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.

NCTSTA

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.)

Image 6. Title card and promotional material for the Proceed/NCTSTA webinar on April 21st, at 2:00p ET with question and answer session and a following day’s meeting called “coffee house chat” where informal discussion and questions were directed at me regarding the topics discussed. It was a fantastic dual session, something I would promote and do again in the future. Unlike the previous hour lecture aimed exclusively at a pathology audience, these attendees came from mixed roles from frontline healthcare workers to government officials in public health and were located all over the US! Here’s the link to the recorded webinar, check it out here.

Who’s Vulnerable?

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!

Image 7a. Some selected slides from the Proceed/NCTSTA webinar on testing and vulnerability. (51) addresses that “tip of the vulnerability iceberg” that goes beyond physical susceptibility to viral infection, (52) clearly demonstrates that the number of confirmed cases in the 5 boroughs of New York City—the hardest hit location in the United States right now—correlates not only to income/expense ratios, but also people of color, and especially those individuals who can’t leave their work because of the “essential” nature of the service industry. (53) This tense situation between paycheck-to-paycheck workers and depending on employment for insurance is point proven if you look at unemployment claims going back to the 60’s! Notice the dramatic spike of 3.3 million claims this year because of the pandemic! That’s more than any oil embargo, dot-com burst, housing bubble, or recession we’ve ever seen! Finally, in (54) I introduce what I think is a “new” type of vulnerable population: individuals who don’t “buy-in” to the science and medical literacy of the current situation. That’s a whole other blog post folks…
Image 7b. Here it is, my COVID-19 Assessment and Preparedness Inventory Toolkit which incorporates data from FEMA, the CDC, the WHO, previous literature on inciting behavioral changes, and evidence-based best practices for addressing the most vulnerable populations.

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.

Image 8. “Operation Gridlock”: re-open protestors in Denver, CO come face-to-face with frontline workers like this nurse in the middle of this tenuous mass protest and battle between politics and science. Scenes like this are happening all over the country like in Ohio, Michigan, and more. (Image: NBC news)
Image 9. ASCP has been the definitive forefront in leading the national charge to address our federal response to proper testing guidelines, strategy, and support. Read more about it here.

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!

Image 10. Lab week 2020, ASCP’s Fellowship of the Lab, One Team to Diagnose Them All


-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.

COVID-19 Laboratory Safety: The Wrong Conclusion?

In the classic Barry Manilow song, Copa Cabana, the singer admonishes his audience at the end not to fall in love. We are told to avoid love because some guy named Rico might exterminate our loved one and we will end up a drunken barfly like Lola in did in the song. It’s a pretty funny conclusion when you think about it. If you were the victim in the story though, you might draw the same conclusion, however flawed. As the COVID-19 pandemic continues, laboratorians are seeing people draw incorrect conclusions as well, and some of those assumptions are leading to some potentially unsafe practices in some laboratories.

It’s easy to understand and even to forgive any misconceptions. The COVID-19 pandemic is unprecedented in our lifetime. The virus is new, it has spread very quickly, and there are unknowns about its make-up and mode of transmission. The situation has changed rapidly, and agencies like the CDC have had to change safety recommendations almost daily at times. Couple that with a media that by its nature uses fear and drama to ensure continued viewership, and people everywhere are going to make some fast decisions, and not all of them will be good.

One example of a change in guidance came from the CDC. At first, they were very careful not to give out any more information for lab safety than what was posted on their COVID-19 web page. When asked if typical lab specimens (blood and urine) from COVID-19 patients could be transported via a pneumatic tube system, they said that all specimens should be hand-carried to the lab. Since many patients were asymptomatic and many more could not be tested because of kit shortages, that would basically mean that all specimens in all hospitals would be carried to the lab. Before hospitals could react or even find the information, the CDC changed its recommendations. Only respiratory specimens from these patients should be carried directly to the lab (https://www.cdc.gov/csels/dls/locs/2020/transport_recommendations_for_covid-19_specimens.html), blood and urine can safely be transported. Given what is known about viruses and other pathogens in blood, walking all specimens to the lab doesn’t sound like a necessary guideline, does it? But this judgement in guidance simply illustrates what can happen when a situation changes rapidly.

With the push for the need for COVID-19 testing, news has come out about specimen collection kits and new and faster testing platforms. Not everything that has been reported has been factual. Every night we see numbers of cases and mortality rates reported in the media. Mathematically, one cannot determine a mortality rate without knowing the total number of patients’ cases. If there aren’t enough test swabs and reagents, and if we don’t test those who are asymptomatic (estimated to be about 25% of cases), how can we calculate any kind of accurate rate? Some laboratories have been pushed to bring on testing, and with little experience with brand new instruments, there has been work performed in some locations without adequate PPE or other safety measures. Look at your testing platform. Review the steps to see if there are any potential aerosol-creating steps. Are the correct PPE or engineering controls in place? Now more than ever it is vital to adhere to lab safety regulations while paying attention to the latest COVID-19 safety guidance. If you feel there is work being performed without adequate safety protection, escalate the situation as soon as possible. There will be no one to run teste if all of the laboratory staff becomes sick.

In many locations, hospitals have responded to the shortage of N95 respirators and surgical masks by developing methods to decontaminate and reuse them. While that is an innovative idea, make sure the system in place has physical and biological checks in place to ensure the reprocessing is effective. Spot test disinfected N95 respirators by performing fit-testing with them as batches are reprocessed. Use a biological indicator to ensure the COVID-19 virus particles have been eradicated. Do not reprocess N95 respirators used for protection against tuberculosis unless it is certain the disinfection process is known to effectively destroy TB bacteria.

Sometimes we come to the wrong conclusion, and sometimes mistakes are made, even in the world of science. But we are human, and we have to come to terms with that or we might end up alone in a disco like the aforementioned Lola. That’s why it’s important that we stop for a moment and pause, especially when an event occurs rapidly and transforms the very environment where we work. Take the time to ensure safety measures are in place for everyone involved. If something doesn’t make sense, question it. Examine it, and work with your staff as a team to make sure we can do what we are called to do- to safely perform lab work in order to provide quality results for the patients we serve.

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.

Tips for COVID-19 Testing

Since I last wrote about some testing options available for COVID-19 testing just 1 month ago, many things have changed in the regulatory requirements, and the companies offering testing options. With that in mind along with the fact that things will likely continue to changes, I’ll write to address current and future challenges facing COVID-19 laboratory testing.

  1. What control material can be used?
  2. How can I make specimens safe?
  3. Supply chain issues and solutions.
  4. False Negative results of COVID-19 tests: what to tell clinicians.
  5. Serology Tests: Future Testing and Challenges

Control Material

As the FDA said contrived specimens could be used, that means that RNA can be spiked into a clinical matrix for extraction. While this began with a requirement for genomic RNA, it has been loosened to include plasmid DNA. However, I would caution against using plasmid DNA, because when it is amplified, it can easily cause contamination and unlike RNA, DNA can persist in the environment for a long time. I once hear a story about a lab director who thought they were very careful, but in pipetting, they contaminated the lab in 3 days and it had to be cleaned up for 4 weeks.

We had some issues using in vitro transcribed RNA (of just the N-gene) and genomic RNA, because the recovery was very low. We found out that intact viral particles were better in optimization experiments using control endemic SARS strains (Zeptometrix controls, Table 1). The free RNA Ct values fell sharply (over 1000-fold) when added to Nasopharyngeal (NP) matrix or Viral Transport Media (VTM). However, much lower levels of the encapsulated viral control had consistent levels of amplification.




Table 1. Amplification of free viral RNA vs. viral particles when added to matrix

Therefore, we used a synthetically encapsulated SARS-CoV-2 RNA sample called Accuplex (SeraCare, Figure 1), which gave good recovery and a limit of detection down to 260 copies/ mL (5 copies/ reaction). Alternative similar material that we have not evaluated include: COVID-19 RNA synthesized inside inactivated E coli (Zeptometrix) and Armored RNA (Asuragen).

Figure 1. Schematic of how a synthetically created viral particle occurs

Lab Safety of Specimens

A safety recommendation of the FDA was to perform extraction of samples in a Biosafety level 2 hood. However, high-throughput extraction can’t be easily done this way. For us, we had to prepare samples in the hood then take them to the stand-alone closed system extractor. Our Micro fellow had the creative idea to do “Off-Board” lysis, which would inactivate the virus in the hood before walking it over. We later found that combining lysis with NP matrix before spiking RNA stabilized the RNA for accurate measurement. We were able to find an LOD of 14 copies/ reaction this way.

Some labs have proposed using heat inactivation (~30 minutes at 50-60C) of virus as a safety measure, but the published literature available on how that affects sensitivity is lacking currently.

Supply Chain issues

You have surely heard about all of the new companies that have come out with new testing platforms and assays for COVID-19 testing by now. However, the downside is that unless you already have their instrument, you likely won’t be able to get reagents in time to perform the assay. Even if you do have an instrument, limited resources are necessitating allocation based on high risk areas, so you are likely to receive fewer kits than you would like. Also, the reference labs are still ramping up capacity and are returning results back with long turnaround times currently (~ 1 week). This supports the strategy to bring the testing in-house, so that you can get results back quickly and have control over at least your labs reagent supply. If you have the instrumentation of another FDA approved EUA, you can start performing testing if you follow that protocol exactly- the CDC is the most widely used.

False Negative Tests of COVID-19

This is hard to assess when only one lab testing modality (PCR) is available, but clinicians report negative results in a patient with classic symptoms and a contact history with a COVID-19+ person. Given the impressive analytic sensitivity of the test (generally 1 copy of RNA in 1mL of sample), the likely explanation is that there is a specimen issue. Proper NP sampling requires sticking the swab to the very back of the nasal cavity. Furthermore, this virus may reside more in the lower respiratory track (lungs) and simply not be present in the area sampled. This is why repeat sampling could be helpful. However, the outcome should be the same whether or not you have a negative test: if you have symptoms you should self-isolate unless you require emergent care due to shortness of breath or other symptoms that can’t be managed at home. The lab is familiar with these pre-analytic limitations that can arise, but it is helpful to explain this to clinicians.

Serology Tests: Future Testing and Challenges

Serology can be very helpful as a separate method from qPCR to determine if someone has been infected with SARS-CoV-2. Notice, that is in the past tense. A small (n=9) pre-print study from Nature indicates serologic conversion starts around day 8 or 10 after symptom onset, which often is not in a clinically helpful timeframe. However, these tests are cheaper and easier to perform, so could be useful for epidemiological purposes to determine who has been infected with COVID-19. Early genetic data indicates that the mutation rate is slow (4x slower mutation rate compared to seasonal flu) as one would suspect for RNA-based viruses, so the virus shouldn’t change enough to cause re-infection in someone with sufficient antibody levels.

Figure 2. Scheme of the first COVID-19 antibody test to receive FDA Emergency Use Authorization.

However, several challenges in interpreting these antibody tests include:

  1. Some conflicting data as to how quickly IgM develops relative to the onset of symptoms
  2. What is the time-line for IgG production?
  3. Ruling out cross reactivity with other strains of Coronavirus that cause upper respiratory infections.

References

  1. Wolfel R, Corman VM, Guggemos W et al. Virological assessment of hospitalized patients with COVID-2019. Nature epub ahead of print. https://www.nature.com/articles/s41586-020-2196-x_reference.pdf
  2. Mitchell S, George K et al. Verification procedure for commercial tests with Emergency Use Authorization for the detection of SARS-CoV-2 RNA. American Society of Microbiology
  3. https://www.livescience.com/coronavirus-mutation-rate.html

-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.

COVID-19 Q&A: Laboratory Safety

The evolving COVID-19 pandemic has changed the world already- the way we educate, the way we conduct business, and way we socialize (or don’t). In the lab setting, there are many practices and procedures that are now being questioned. Sometimes the answer changes quickly, sometimes there is national guidance to assist with a particular issue, and sometimes your own facility or organization makes the decisions for you. As a lab safety consultant, I have received many lab safety questions about handling certain situations in these times, and I want to share some of those because others may be wondering the same thing.

Q: Should nurses or other staff come into the laboratory wearing surgical masks, even if they are taking care of COVID-19 patients?

A: Yes, it is acceptable and safe for nurses and other staff to enter the lab wearing surgical masks (unless a company policy prohibits it). Remember, if someone else wears a surgical mask, that protects you, NOT them. Even if the employee is taking care of a COVID-19 patient, science tells us that virus particles are not falling off their mask. It is generally safe for people to enter the department wearing a surgical mask.

Q: Should nurses or other staff come into the department wearing gloves?

A: No, it is generally not acceptable for others to enter (or exit) the lab wearing gloves. Door handles should be considered clean. If specimens are being delivered, the outside of the bag/container being carried is considered clean (even if a COVID-19 specimen is inside). Post signage to remind non-lab staff to remove gloves, and notify people immediately if you see them using gloves to enter or exit the lab.

Q: My lab co-worker seems to be sick. Can I tell them to go home or self-quarantine?

A: No. As an employee you do not have the right to approach a co-worker or dictate to them how to proceed. If you have concerns, escalate them to the manager. If you’re the manager, contact your employee health department. That is the department that can best determine who needs to be sent home for isolation. Remember, there are many other reasons people cough, sneeze, or have a runny nose. For instance, allergy season is in full swing. Harassing a co-worker about their health would be considered a violation of Human Resources policy.

Q: How does laboratory staff maintain an appropriate social distance from each other while working?

A: The answer to this really depends on your lab set-up and processes. Is it possible for staff in smaller labs to change work patterns in order to better maintain a distance from co-workers? Try a different receiving location so that those from outside the department can drop off specimens from a distance, like placing a cart near the lab door. Some facilities require masking of all staff, and if that is the case, then social distancing while at work may not be an issue. Be sure to limit staff in break rooms as well, and make sure areas are disinfected regularly.

Q: Should autopsies be performed during this pandemic?

A: Some pathologists have suspended autopsies at this time. While it is possible to perform autopsies on COVID-19 patients safely using the appropriate PPE, many deem the use of such PPE to be unnecessary when so many others need it.

Q: Can PPE be disinfected and re-used safely?

A: Some locations have moved to reprocessing N95 respirators, surgical masks and isolation gowns. Make sure there are appropriate quality and safety checks being performed on this equipment before it is re-used. While some methods can disinfect items used for COVID-19 patients (i.e. UV light treatment, hydrogen peroxide mist, etc.), they have not been approved for the disinfection of tuberculosis. Therefore, if PPE has been used to protect staff from TB, it should not be reprocessed with the other PPE used for COVID-19 patients.

Q: Histology and cytology slides from fresh (unfixed) samples are made in the lab space and moved to offices for reading. Can these slides from potential COVID-19 patients be safely read in clean office areas?

A: This is a valid question at all times, not just during this pandemic, and the answer depends on the process used for making the slides. It is known that xylenes or solutions containing 60% ethanol or more easily inactivate COVID-19 and other pathogens. Slides made with these chemicals can safely be transferred to office areas for reading. Fresh tissue/sample slides using other methods (i.e. methanol fixation) should be read in the lab space only. Check your reagents in your slide stains to see if they eradicate pathogens. If not, check to see if it is possible to fix the slides in stronger ethanol solutions before staining.

These are just some of the many questions people are asking. There are references which can help to provide some of the answers (CDC.gov, WHO.int, OSHA.gov, etc.), but if you need more lab safety information, please feel free to send me questions at info@danthelabsafetyman.com. I will provide the most current safety guidance for your issue. This is a rapidly-changing situation, and information comes from many sources, Make sure you do your best to validate what you hear, and continue to use Standard Precautions and good behaviors to keep you and your laboratory staff safe from COVID-19 and other harmful pathogens.

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.

What Does Patient Advocacy Mean for Pathologists?

As pathologists, patient advocacy and safety have quite unique meanings as compared to our colleagues on the wards and in the clinics. It is such a unique opportunity to affect further care and treatments, depending on how testing is used. I find the combination of patient advocacy within the clinics an opportunity for pathologists to possibly meet patients and learn from our clinical colleagues about how much the lab truly affects patient care. 

At my institution, we have what is designated as “Diagnostic Management Teams” (DMT). At each DMT, our clinical pathology teams perform actions such as writing interpretations for difficult test panels or review the charts to make sure teams have changed their patients to the proper antibiotics. . In our coagulation DMT, we write the interpretations for complex esoteric coagulation studies to ensure: 1. the right tests were ordered, and if they weren’t, we recommend which are appropriate, 2. these complex tests are explained in a way that is understandable to our clinical colleagues and 3. proper patient care and safety for tests which are very critical to patients. To add a layer to this complex testing system, we also have the opportunity to attend benign hematology clinic with one of our attendings. I found this experience to be rather eye opening. Pediatrics hematology clinic is an interesting place whose patients are diagnosed with a wide variety of diseases. A vast majority of these pediatric patients have a parent who has been deemed a “bleeder” or a “clotter” at some point in their lives, or the patients themselves have exhibited such conditions. Often, the parents do not have a definitive diagnosis, and so the investigation begins. The hematologist, who also is one of the coagulation DMT attendings, will order panels which fit with clinical history not only on the patient but more often than not on their parents as well. This allows the DMT to analyze the nuances of the complex coagulation system, even down to multimer gels to figure out which type of von Willebrand disease a patient may have. Although these clinic visits may seem superficial, they give families such a comfort to know a classification of their disease, how it can be treated and if it has been passed down to the actual patient, their child.  One such instance, we actually produced a family pedigree with the type of von Willebrand disease within them and then did confirmation testing. Seeing the delivery of information and subsequent relief on the patients’ faces is always a gentle reminder of how much we affect and advocate for our patients in the lab, which starts with the order or a “simple test.”

-Melissa Hogan, MD is Chief Resident  in her fourth year in anatomic and clinical pathology at Vanderbilt University Medical Center and will be starting her Cytopathology fellowship at VUMC in 2020. She is currently Chair-Elect of ASCP Resident Council. She is passionate about patient care and medical education.

COVID-19 and the Rural Laboratory

When I was approached about writing an essay about our rural lab, I was initially stymied. There’s a universality about the work we do; tech work is pretty much the same wherever you go. A differential is a differential in the biggest cities and smallest towns. The thing that makes us unique is that we’re 50 miles from a city with a full-service hospital and many of our patients are elderly and don’t drive, so we try to cobble together as much care as we can give them in a clinic setting.

Our clinical laboratory is a small independent lab in Cairo, IL, midway between Memphis and St. Louis. We are attached to a regional system of rural clinics that provides care for the residents of the poorest counties in Illinois. We are the only high-complexity FQHC lab in the country, and we’re extremely proud of the work we do with our limited financial and geographical resources.

Our part in battling the COVID-19 pandemic feels a little odd compared to the work of hospital labs. We see our job as keeping our patients out of the overburdened hospitals for as long as possible. We screen everyone who presents with a fever for flu and strep. That includes the prisoners from the two local prisons, the nursing home patients in all the small towns scattered around rural southern Illinois, the teachers, daycare and home health workers. The criteria for a C-19 test is still very stringent in Illinois and most of our patients don’t yet meet it. We generally send them home with free samples of over-the-counter palliative meds, instructions about avoiding other people, and what new symptoms they should watch for.

Even so, we’re running low on basic supplies: PPE, swabs, disinfectant, etc. Like everyone else, we’re having trouble finding more. Yesterday I took a couple of hours to open every cabinet and paw through every box, hunting for overlooked supplies. There was a stash of sixty N95 masks in a closet and forty painter’s masks left over from when the lab was built. The box claims the masks “have N95 properties”…whatever that means. Hopefully we won’t have to find out. I distributed the N95 masks to the clinics that were running low and traded a box of disposable lab coats to our local clinic for 3 hazmat suits for our lab staff. I sent a few dozen more nasopharyngeal swabs to the prison with instructions to use them sparingly. We’re currently backordered until mid-April for more.

All the techs I know (locally and all around the country) are pretty fatalistic about this. We expect to be infected. We’re hoping it’ll be later rather than sooner and we’re trying to protect our more medically fragile and/or elderly colleagues. As you probably know, the average age of MTs in this country is about my age…56. A new virus brings attention to the medical lab profession, and that causes a brief uptick in new interest in our field, but we’re chronically understaffed and techs are retiring faster than we can train new ones to replace them.

In the meantime, of course, we continue to test and treat our regular patients. Mostly poor, mostly elderly, for the diabetes, hypertension, cardiovascular diseases and cancers that are the meat and potatoes of rural health. The concession they’ve made to social distancing is that less of them hug me, although a fair number say “If it’s my time, it’s my time” and hug me anyway. Many of our patients don’t drive, and they arrive one by one on the transit vans designed to seat 12 that pick them up from home. I wonder if the van driver disinfects between patients. I wonder if the patients know he ought to. I assume they hug him, too, so it probably doesn’t matter. This coronavirus crisis will eventually wind down, but the ongoing needs of medically underserved rural communities will continue unabated. Our hope is that this pandemic shines a big light on the many challenges of providing quality care to geographically large, sparsely populated rural communities.

-Evelyn Rubinas is a Medical Technologist at Community Health and Emergency Services, Inc. (CHESI) in Cairo, IL. She is a graduate of Southern Illinois University and the University of Arizona and has been a laboratory generalist for over two decades. She lives in Cairo, IL with her wife and a small menagerie of rescue animals.

Testing (Our Patience)

Hi everyone, and welcome back!

I’ll get straight to the point this time: there’s a legitimate crisis happening in our world that is highlighting a multitude of things. Just to name a of few: the complex intersection of state-sponsored healthcare as a human right, the availability of resources to clinical personnel, the logistics and implications of public health measures to the average person, our global connectivity, and lack of damn tests!

And that’s our stop. Please take a minute to locate your exits, as they may be behind you, and get ready to talk about this SUPER CRITICAL aspect of the COVID-19 pandemic. What are clinical tests?

I know, this “viral” topic right now will be shared and spread to a vast array of audiences. So, I’m going to try something new here. The last four years of posts on this blog have been aimed somewhere between laboratory professionals and working clinicians. I open a rare window into our clinical world from time to time, but this pandemic is something affecting everyone. Today, we’ve got a major problem about what’s being said in the media and who understands which parts of it…so, as I discuss some major points below, I will take short pauses to highlight clinically relevant information as well as put things in plain, simple terms for all of us to get up to speed together.

(If you are one of my clinical colleagues, from the bench to the bedside, your notes will be in BLUE. If you are not in the healthcare world, or just want some simple clarification, your notes are going to be GREEN. Let’s run an example so you can see what I mean…)

Image 1. I realize that there are people who ware blue-green colorblind, so if you have a hard time differentiating one from the other in this picture, I’ll keep the clinical/general labels. If you have no issues with these colors, the image above uses green to demonstrate where the coronavirus pandemic currently exists. Colorful humor? Fine, keep reading…

Last month I talked about the background and biology of the SARS-CoV-2 virus as a novel, emerging pathogen and potential pandemic and discussed how we must contextualize these epidemics with proper understanding of data and statistics. Numbers are important and if we’re going to combat a super bug, we’ve got to know what it is, how it acts, where it came from, and what’s happening in the field. A subsequent and fantastic post right after mine by Dr. SoRelle at UTSW, discussed how to validate a COVID-19 test in your laboratory. Basically, he presented a snapshot of the current climate of academic hospital labs now depending on LDTs to respond to the pandemic and discussed where to read more, what limitations testing might have, and how to address things like designing/purchasing primers, cross-reactivity, detection capabilities, and EUAs under the new FDA guidance.

But back to business, this month we’re talking about testing, and if you just google search “COVID-19” in the states, you’re met with a myriad of failure stories…

“As US fumbles COVID-19 testing, WHO warns social distancing not enough” (source)

“Limited access to COVID-19 tests frustrates patients, health professionals” (source)

“What went wrong with coronavirus testing in the US” (source)

“Why coronavirus testing in the US is so delayed” (source)

“America’s shamefully slow coronavirus testing threatens all of us” (source)

Image 2. This novel coronavirus pandemic has caused another pandemic of fake news. Fake cures, misinformation, false panic, mistrust, and a whole mess of non-scientifically accurate claims that have slowed the responses of public health officials in China, Italy, and even here. (Image source: BBC)

I’ll stop torturing you. You’re forced to watch and/or read enough news as it is nowadays (you’re social distancing, right? …right?) I mean, even Norway took a jab and called us “underdeveloped” citing our poorly developed healthcare delivery system—ouch. So, what’s the big problem with testing? What stark revelation exists between all these different news sources and highlights our “laboratory failures” in America? Well, luckily nearly all of these lab-fail stories aren’t aimed at our labs at all, they’re aimed at governmental decisions and red tape traps. But that’s hard to get to in a sea of clickbait. So instead of giving you more rabbit-hole lab talk, let’s talk about two main tenets of this narrative that everyone should be aware of: what laws affect lab tests and what does it mean to create a new lab test? After we clear the air for those two key points, we’ll come back around and tell you what COVID-19 looks like in the medical laboratory.

The Law of the Lab

There are SO MANY regulations and accrediting bodies that govern the way labs operate, deliver results, and function in clinical settings. Let’s name some! Various federal, state, and local laws ensure the highest calibers of safety and accountability for clinical and research laboratories; laws from OHSA, the FDA, recommendations from the CDC and local health departments; regulations for mechanical, noise, chemical, exposure, pathogen/infectious safety, pollution, radiation, blah blah blah! Trust me, there are a ton. What feels ever present to us laboratorians are the accrediting and inspection agencies that grant us authority to continue performing our clinically vital roles. Joint Commission, FDA, and other inspections make sure hospitals are up to snuff. Laws that govern what labs can do what tests fall under CLIA. They help us define high complexity to waived (not complex) testing. There’s a massive difference in a clinical office’s medical assistant obtaining a point of care (POCT) glycated hemoglobin (Hgb A1c) than a medical laboratory scientist conducting a hemoglobin electrophoresis study, and that difference highlights specialized training, laboratory ability, safety and quality requirements.

Image 3. I know we’ve had this debate a few years ago, but your average nurse probably couldn’t help too much with a bone marrow aspirate evaluation or running quality control on the chemistry analyzers before morning run. Just the same, I remember being an MLS and I wouldn’t have been the most confident IV or foley catheter placer…now I have the distinct pleasure of living in both worlds. Yay. Bottom line: the laboratory, and de facto the hospital, COULD NOT FUNCTION without the team of medical laboratory scientists that make its wheels turn! (Image source: labtestsonline.com)

Accreditations and recommendations can come from many professional societies like the CAP, ASCP, AABB, AACC, ASM, ASH, and many subspecialized groups. Laboratorian trigger warning: I’m a certified CAP inspector. No; you don’t have to put away your desktop coffee…for now. But I’ve certainly—along with all of you—been wholly immersed in the endless accreditation and regulation protocols we follow. We know exactly why these regulations exist and we should talk more about them, since they define our role as such a critical one.

Feeling Validated Yet?

Some of you lost a breath when I said CAP inspector. The rest of you may now spit out your coffee and run for the hills because I’m talking about VALIDATIONS. Rotating MLS students sometimes do their capstones or theses on validating a test or instrument, but we do them because that’s just a part of our job! So what goes into validating a test? The short answer: a whole lot. The long answer: a whole lot more! Let’s take PCR testing for example, it’s topical because we’re talking about COVID-19 testing and that’s the prime modality so let’s explore that validation.

Image 4. A LOT goes into validation. Lots of biostatistics. I know there’s labels, but let’s walk through this graph. The red line is the best line, good correlation with minimal errors. The purple/pink like is permanently off the red line, therefore its in constant error. The blue line represents errors associated with too much or too little specimen, maybe too little reagent, or some other ratio issue. The salmon line might be another test, or another method of the same test. What do you think? Is it a better test? A little sharper of a test, maybe more sensitive, should we use less specimen? Maybe just a drop or two—BAM you’ve been sued for running a sham lab test company. Trade in that black turtleneck, do not pass go, do not collect $200. A newly validated test, or a validation of a new method comes with BINDERS full of runs and analyses, not for the faint of heart. (Image source: AACC)

So, you want to add a qPCR to your lab’s test menu, eh? You first have to decide quantitative or qualitative. If its quantitative you’re in for a treat—yay statistical variant analysis! You have to prove applicability, practical application, specificity, sensitivity, efficiency, correlatable translation into useful clinical data. Detecting a number or degree of mutations? Make sure its accurate and precise (and repeatable). Buying commercial kits or making your own in-house assay? What about a qualitative test, just a simple yes or no. Easier right? Not really, you need to prove most of the same data and statistical soundness depending on methodology used, instrumentation, nature of variation, etc. AND: it all must be documented, proven, up to regulatory standards, and you better have a database FULL of data that proves your test works. Now, I have good news and bad news.

The good news: this is pretty routine, and pretty easy to follow even for simple new tests your incorporating from commercial vendors with ready-to-validate test kits. The bad news: COVID-19 is not this type of test. Say what you will about the US’s decision to NOT utilize the WHO testing model available weeks ago, the CDC responded in kind here by providing a two-control kit that SLOWLY started to break out. Using this as a model, many labs in academic hospital pulled the trigger on their LDT work. (LDT = laboratory developed tests) I’ve already revealed myself as a CAP inspector (pshh, not even my final form!) and I can tell you that there are hundreds of citations for how to validate already existing tests, compare tests across different instruments, compare them across the same instrument, prove your statistical ability to ensure quality results, and even how to make your own test from scratch! Talk about extra work!




Image 5. [MLS]: You’re a good analyzer, a smart analyzer. We all appreciate your efforts and you’ve really contributed to a positive work environment. We appreciate you, so we got you these reagents. They’re nice and fresh, what do you think? [Instrument]: *BEEP* *BEEP* *ERROR* *MORE VALIDATION REQUIRED*, [MLS]: okay, okay, have you lost weight?…**RESULTS VERIFIED** (Image source)

Running COVID-19 testing alongside B. burgdorferi: Corona…with Lyme?

Now we’ve come to the heart of the current discussion. Dr. SoRelle talked about validating a COVID-19 assay last month, so I’m letting him take point on that—read his piece, its great! What we’re talking about today is what exactly regulations and validations have to do with COVID-19 testing. Remember the regulations that say how laboratories run tests and operate clinically? Okay, well there are issues with this narrative. You’ll see plenty of news stories about the regulatory red tape that has hindered lab professionals from providing COVID testing. This makes it sound like because of “rules” we just can’t give them out to everyone, or we can’t set up testing for whatever regulatory reason. This is not the case. This is how the relationship between those aforementioned regulatory bodies work. The FDA makes sure labs operate up to federal standards and, and specifically, enforce regulations outlined in CLIA. While the FDA would like to call tests/results products of analyzers/devices to fall in their prevue, the interpretation and translation of that clinical data is not a print out but a MEDICAL SPECIALTY—hi, I’m pathologist #2465827, part of the FDA regional lab result response team—nope. Lab developed tests (LDTs) are not FDA products, but CLIA certified processes that only CLIA certified laboratories can perform. No CLIA no LDT—it’s as simple as that. You now understand that a lot goes into a single test, and that not every lab can perform high-complexity testing, thus, not every lab is CLIA certified to do LDTs… which means no COVID testing for them.

Image 6. It’s not that there aren’t enough tests. Like we ran out or something. This very fast global pandemic happened and pulled the rug out from under us. Because of a number of challenges, we’ve just been behind developing a NEW test for a NEW bug. And we’re catching up quick, but like ASCP addressed their concerns to the White House, we are in need of resources and support. Vendors can’t just jump in and help because THEIR hands are tied by the FDA even if they have readily available test kits. Other countries have done better than us, and we can still do better. (data as of 3/14/2020, source: AEI)

Okay, the other half of the narrative says that because of a lack of supplies from industry vendors, commercial kits were unavailable either from them or the CDC and if they got them, their reagents were not good. Frustrated, scorned immunology/chemistry lab specialists decide, “we’ll show them…we’ll make our own test! *evil laugh*” A bit dramatic, because it is dramatic. That’s not how LDTs work. How, then, do we get to LDTs? That answer is simple: regardless of politics, resources, or any other social concerns, medical laboratorians and clinical pathologists are part of the essential healthcare team that strives to care for the sick and hopes to prevent unnecessary infection or illness. We’re in this together and if one system can’t provide tests for the whole country, hundreds of thousands of hospitals will rise to the occasion and share partial LDTs or create their own. Just like with any other test, labs know full well how to get this done and work together to do it.

But what about the stories that say some tests take 8 hours vs others that take 4 days to turn around results? How come some kits came with 2 swabs, and some with 3? Why did other countries like South Korea do a lot better than us in testing their population? Did we wait too long to set up LDTs? Can’t I just go to my doctor and get tested now? Okay, okay, I hear you. This is where it gets heavy, especially in the media. The takeaway can be a simple comparison: look back to the Zika epidemic. Zika is an Arbovirus/Flavivirus that we knew about for roughly 60 years. As such, we had time to understand it and create tests quickly that measured exposed patients’ antibody response to acute or resolved infections. Even simpler, Zika is part of a family of mosquito-borne illnesses that we generally understand pretty well. SARS-CoV-2 is not like Zika. The word “novel” is used because it’s just that: brand spankin’ new. And, even though it’s a cousin of its predecessor in the old SARS epidemic, we’ve been racing the clock to create accurate and reliable testing. That’s why there’s so much variability happening across commercial industry to academic hospital laboratories.

Image 7. We’ve got a lot of work to do. At a rough estimate there are roughly 6000 cases of confirmed COVID-19 in the US, and we’re only testing that much…we can’t even collect this data fast enough. This is was scares most healthcare people, myself included. (Source: Medscape)

Pandemic Proportions

I love to make puns but let me be clear: this is a serious global pandemic, as defined by the CDC and WHO and we must understand this fully and appropriately. We’re still in the dark about a lot of data, mostly because of missing numbers. What we do know continues to inform our daily-changing climate of public health awareness in the US. The following images speak for themselves and I’ve collected them as a resource and snapshot for you to look through, just to get your SARS-CoV-2 bearings.

Image 8. If you haven’t yet locked this into your computer desktop, this dashboard from Johns Hopkins pulls data from various trusted sources (WHO, CDC, ECDC, NHC, and DXY) and local info to create a live, updating dashboard to follow along with the pandemic. (Source)
Image 9. I posted these for my pieces on Zika in Sint Maarten, so let’s not be strangers to the epidemiological week graph. Take note, after the first week of March 2020, things get messy. Read: the great lab test debacle. (Source: CDC)
Image 10. This is an uncomfortable graphic. Outside of China, the worse of the (then labeled) epidemic was Italy. Fast forward, we’re in full global pandemic mode and we’re starting to overtake the Italians a bit with cases detected/reported over time. Living, breathing, coughing data. (Source: @elipariser on Twitter)
Image 11. Could I write a piece about literal lab testing and ignore this gem of a post from @TrustMeImAMedTech ? No, I could not. Very cool, clinical snapshot of an average COVID-19 patient’s labs based on data from a Clinical Chemistry Lab Medicine article from this month.
Image 12. The UCSF ID working group established a diagnostic profile of a suspected COVID-19 infected patient. Anecdotally, I’ve read about cases that present with lymphocytopenia or lymphocytosis, the latter of which may correlate to prognostic factors. (Source: J Babik, UCSF)
Image 13. What? I’m still on Reddit. There’s always good stuff on there. This post by u/RadOncDoc shares intensivist Dr. Nick Mark’s take on acutely infected, critical COVID-19 patients. I’m reading and absorbing… (Source: reddit, r/medicine)
Image 14. You’ve heard of #FlatteningTheCurve, what does this mean? If we do nothing, the daily number of cases increases dramatically. If we take measures to preserve the capacity of the health care delivery system (social distancing) we won’t over tax the ERs and critical care units that might be needed during this pandemic, thus, flattening the curve of daily cases. (Source: Vox)

What can I say? It’s hard to write a conclusion about something that’s changing every day. I’ve been doing my best editing to keep this as up to date as it could possibly be for publication, but there are a million more resources sitting in the queue that I wish I could walk you all through. But I think, at the end of the day, what we need to remember is one simple thing: we’ve been here before and we’ll be here again. Public health epidemics and our responsiveness is one of the more serious aspects of laboratory medicine and pathology, not to mention healthcare at large. I said it last month that we’re lucky that this isn’t an influenza-type virus, because that would look a lot different. There are still some highly serious infectious etiologies out there more lethal than COVID-19, but this pandemic is bringing to light a lot of public health awareness and an opportunity to examine our population’s medical/health literacy, our policy priorities, our strength and resolve, as well as our ability to adapt.

Image 15. If you have a few minutes, please watch this CNN clip from one of my friends, colleagues, and mentors discussing how to be safe and smart during this period of social distancing and compassion-informed protective changes! (Source: CNN, video here)
Image 16. “I’ve never seen anything like this before,” said the pundit, reporter, bystander, and/or concerned citizen. The sad part is, they say it every time we have a public health crisis. The time is now to break the cycle and learn from the past. (@CEKanakisMD, #PathDoodles 2020)

In the coming days, weeks, months you’re going to most likely hear about municipal infrastructures cutting back on things in order to prevent the spread of the virus. Listen to these warnings and heed the advice of the medical community. If you think you’re being a hero by braving the storm, you’re no better than a mosquito that carries malaria with no symptoms itself. Wash your hands, practice appropriate social distancing, continue your daily life with your necessary trips out being mindful of what those of us in healthcare live with on a daily basis. Practice compassion as well, just because we’re social distancing to “flatten the curve” doesn’t mean its time for martial law and cleaning supply hoarding. I know these are serious times, but humor and compassion can be infectious too.

Thank you for reading.

Please remember to follow the most updated, verified, and trusted sources on this starting with the CDC and your local public health organizations.

Wash your hands. Change your clothes. Minimize exposures. Take time to reflect and keep as close to your normal routine as possible while remembering things will get better.

If you have specific questions, comments, or concerns leave them in the comments below. Feel free to contact me anytime, and follow my social media (@CEKanakisMD on Twitter) for more/updated material.

Take care, see you 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.

Playlist for the Apocalypse and Other Rays of Hope…

While washing my hands in an airport restroom, “Until the End of the World” by U2 (Achtung Baby, 1991, Island Records) was playing over the toilet speakers. As I watched several people incorrectly wash their hands during this current pandemic, the songs lyrics (which I have known by heart since 1991) rang through my brain and struck a new chord with me. There are plenty of doomsday songs that actually make us happy (Prince’s 1999, from 1999, 1982, Warner Bros.; R.E.M.’s “It’s the End of the World as We Know It,” from Document, 1987, I.R.S. Records) despite the dark images in the lyrics. And then here are a whole host of doomsday songs that are dark and brooding (“Man Comes Around” by Johnny Cash, “Waiting for the End of the World” by Elvis Costello, “It’s Not the End of the World but I Can See it from Here” by Lostprophets, and “Preaching the End of the World” by Chris Cornell, etc.). It turns out you can write a doomsday song after a breakup with your partner (“The End of the World” by Skeeter Davis) or in response to nuclear war fears (“Everyday is Like Sunday”by Morrissey).

What struck me in my new feeling of U2’s track was the dichotomy of viewpoint by the two principal voices in the song. The speaking voice is in it for the short game, in it for “me.” The listener in the song is in it for the long game, in it for “we.” Considering both the inspiration for the song personally for Bono as well as the historical character about which the song is based, this might be kind of obvious to most of us. However, in 2020, as we face what can only be described as a venomous divergence of voices, the lyrics force me to think about individuals’ motivations, agendas, messages, points of view, and goals when they speak, text, post, or otherwise communicate their opinions and that such opinions come in two flavors. There are those that are in this for themselves. There is no other valid observation than selfishness, conceit, arrogance, and disrespect for others. There are those that are in this for everyone. There is no other valid observation than collaboration, caring, selflessness, humility, and respect.

Considering that, regardless of your moral compass or who your parents were, most children are theoretically raised to be like the latter but the innate, instinctive traits of our evolution are really the former. Thus, as many great philosophers and thinkers have concluded, the intellectual evolution of the human mind and personality is such that seeing and caring for “the other”, even more than for ourselves, is a mark of high achievement while base, crude attacks on “the other” are marks of devolved, unintelligent individuals. Notice that there is no good and evil in this argument. There is only awareness of self and awareness of others and choosing one over the other. Naturally, the best life is to balance our care for ourselves and our care for others, which, some would argue, is one of the most valuable aspects of organized religion. As I am a non-religious person—despite the fact that the U2 track is one of my favorites—I strive to achieve that balance through a universal moral compass perspective which includes a great deal of importance on the safety, security, health, well-being, and happiness of others.

COVID-19 and its viral cause, SARS-CoV-2, have sent incredible ripples, waves, and tsunamis across every aspect of human life in the last 6 months. Pandemic preparedness and responsiveness is a “we” activity. China very much had a “we” approach to health (among many other sectors) which was evident by their incredible response to SARS originally in 2002. Some would argue that had SARS emerged in any other country, it would have gone pandemic at a much faster rate with horrible consequences; yet, emergence in China meant the virus was facing a huge pre-programmed response. But importantly in the 2002 outbreak, CDC officials from the US were relocated to China and work closely with the Chinese government to plan, implement, and execute daily changes to the management of the outbreak. Relationships being what they are, China did not interact as closely with the US for COVID-19 and, thus, the response was not as successful. In healthcare, as in many areas of human life, we are stronger together, and we will be more successful with transparency and communication than with secrecy and seclusion. The health of humanity should not be a geopolitical issue.

The diagnostic medical team (DMT), composed of pathologists and laboratory professionals, is the backbone of modern healthcare. However, these are also people who have underlying conditions, have elderly parents, have to ride the train to work, etc. Everyday, even when there isn’t a pandemic, members of the DMT place their own personal health and safety on the line to provide patients with rapid, accurate diagnoses and continuous care. Fortunately, laboratorians are well versed in protecting themselves within the laboratory from potential risks; however, in a pandemic situation, they must also protect themselves from external risks, else the laboratory staffing falls below the levels that insure high quality patient care is available.

COVID19 testing by RT-PCR of SARS-Cov-2, for example, is a high complexity laboratory test that is often performed by a select number of laboratorians and not by all laboratory staff. When we hear discussions of laboratory testing for COVID and money for such testing or availability of kits, it must also be noted that the laboratory is the only segment in the system who can take money and tests and turn it into data that saves lives—but only if they have sufficient people to make this happen. Healthcare facility leadership and national leadership must support those teams by providing all necessary resources to meet the needs of patients including the laboratory direct and indirect needs. Expanding the ability of personnel in the laboratory to meet this emergent need through cross-training and potential emergency staffing coverages is essential to successfully navigating this pandemic.

The DMT is always practicing the “we.” But now that the pandemic requires transparency and communication for success, the entire health system must amplify the practice of “we” and advocate with external leaders for every member of the healthcare team, but especially the laboratories. It is no time for “me” in this situation. Hand washing, social distancing, and self-quarantine may seem like things that protect “me” but it is clear that the goal is rooted in protecting “we.” Flattening the curve may prevent the healthcare systems from becoming overburden; however, laboratories are going to be massively overburdened regardless. Asymptomatic, symptomatic with other diseases, and true cases of COVID19 all have to be tested and there isn’t a precedent for the pace the disease is moving. Laboratories are coming online this week (March 16th) with testing that needed to be available in January. Laboratory staff must be enabled and mobilized to meet this current needs. We are all behind the curve on this one, but I have full confidence in our DMTs to get this done if they can be supported. There will be struggle but the tenacity and perseverance of our nation’s laboratory professionals and pathologists will see this through to its end. Because we, the DMT, don’t have a choice but to always consider the “we” in our daily practice, our patients WILL BE tested and diagnosed. We will beat this together and in being together, we will be stronger.

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-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.

Be Safe…Be Very Safe

In the 1986 remake of the horror film “The Fly,” the character played by actress Geena Davis has a great line. When she warns another person about the extremely unsafe behaviors of the title character, she says, “Be afraid…be very afraid!” Clearly this woman in the story understands the dangers involved in hanging out with a man whose mind is slowly being dominated by a killer creature. As a lab safety professional, one of my greatest wishes is that laboratorians would understand the danger they can be in when they permit unsafe behaviors in those around them.

Coaching fellow lab workers about safer behaviors is perhaps one of the most powerful and important tools we have to improve the overall safety culture, but it is also one of the most difficult tools to use. There are a variety of reasons we don’t do well with speaking up when we notice unsafe activities. Some laboratorians are introverts, and saying something that could be perceived as forward or direct just isn’t natural for them. There are those who do not want to correct co-workers or friends since doing so might somehow damage the relationship. Others don’t say anything because doing so in the past had no noticeable results.

The damage done by not coaching others for safety is terrible, and unfortunately, it’s easy to do. Repairing this damage, on the other hand, can be a slow and difficult process. Albert Einstein said, “The world is not a dangerous place because of those who do harm, but because of those who look on and do nothing.” That means that when we see unsafe behaviors, we have a responsibility to do take action against them. Otherwise when we do nothing, we are essentially giving permission for those dangerous behaviors to go on. That will only lead to a worsening lab safety culture, and eventually there will be increasing amounts of injuries and exposures.

With the rapid spread of COVID-19 in the Unites States, the number of questions that have arisen about lab safety has climbed exponentially. I am excited about any uptick in interest in laboratory safety issues, but I wish it didn’t take a world-wide pandemic to cause it. The Centers for Disease Control (CDC) has offered very good lab safety instruction for the processing and testing of COVID-19 specimens          (https://www.cdc.gov/coronavirus/2019-ncov/lab/index.html), and virus testing is being performed in more labs each day.

It is vital for laboratorians to remember this. While the coronavirus is not to be taken lightly, the patient specimens we handle every day contain biohazards that are far more dangerous to us than COVID-19. Hepatitis, HIV, select agents, and many other pathogens reside in the blood and body fluids processed and tested in laboratories across the country, and many of the illnesses these agents can cause are very hazardous to human health. I hope we remember that when the hype about this latest virus passes.

Use Standard Precautions when working in the laboratory. Wear lab coats, gloves, and face shields. When you see a co-worker who is not properly attired, offer them the PPE they need. If you see an unsafe practice like eating, drinking, or using cell phones in the department, end it quickly. That is how infections occur, and that is how they spread into the community. Remember, unsafe behaviors can have a direct affect on the safety of the entire team. The sooner we can help everyone to understand that, the better we will all be at coaching others. In the original 1958 version of “The Fly,” the title character is caught in a spider’s web. His famous (and often imitated) last words were, “Help me! Help meeeee!” The scientist practiced unsafe behaviors until it was too late to turn back. Don’t let that be the case for anyone in your laboratory!

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.