On March 9 my team was given a directive by the chief medical officer of our health system. It seemed like an impossible task, involving the mobilization of people, processes, and technology at a scale and speed we had never before achieved. It turned out getting this done was impossible. In spite of our best efforts, we failed to meet the deadline – it actually took us 3 days. Still, by March 12, we had opened the doors on the first community testing site in our area and gained the attention of local and national news outlets for our accomplishment.
Dr. Chris Notte and Dr. Neil Skolnik
Now more than 2 months later, I’m quite proud of what our team was able to achieve for the health system, but I’m still quite frustrated at the state of COVID-19 testing nationwide – there’s simply not enough available, and there is tremendous variability in the reliability of the tests. In this column, we’d like to highlight some of the challenges we’ve faced and reflect on how the shortcomings of modern technology have once again proven that medicine is both a science and an art.
Our dangerous lack of preparation
Prior to the coronavirus pandemic, I had never considered surgical masks, face shields, and nasal swabs to be critical components of medical technology. My opinion quickly changed after opening our drive-through COVID-19 site. I now have a much greater appreciation for the importance of personal protective equipment and basic testing supplies.
I was shocked by how difficult obtaining it has been during the past few months. It seems that no one anticipated the possibility of a pandemic on this grand a scale, so stockpiles of equipment were depleted quickly and couldn’t be replenished. Also, most manufacturing occurs outside the United States, which creates additional barriers to controlling the supply chain. One need not look far to find stories of widespread price-gouging, black market racketeering, and even hijackings that have stood in the way of accessing the necessary supplies. Sadly, the lack of equipment is far from the only challenge we’ve faced. In some cases, it has been a mistrust of results that has prevented widespread testing and mitigation.
The risks of flying blind
When President Trump touted the introduction of a rapid COVID-19 test at the end of March, many people were excited. Promising positive results in as few as 5 minutes, the assay was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration in order to expedite its availability in the market. According to the FDA’s website, an EUA allows “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions.” This rapid (though untested) approval was all that many health care providers needed to hear – immediately hospitals and physicians scrambled to get their hands on the testing devices. Unfortunately, on May 14th, the FDA issued a press release that raised concerns about that same test because it seemed to be reporting a high number of false-negative results. Just as quickly as the devices had been adopted, health care providers began backing away from them in favor of other assays, and a serious truth about COVID-19 testing was revealed: In many ways, we’re flying blind.
Laboratory manufacturers have been working overtime to create assays for SARS-CoV-2 (the coronavirus that causes COVID-19) and have used different technologies for detection. The most commonly used are polymerase chain reaction (PCR) tests. In these assays, viral RNA is converted to DNA by reverse transcriptase, then amplified through the addition of primers that enable detection. PCR technology has been available for years and is a reliable method for identifying DNA and RNA, but the required heating and cooling process takes time and results can take several hours to return. To address this and expedite testing, other methods of detection have been tried, such as the loop-mediated isothermal amplification (LAMP) technique employed by the rapid assay mentioned above. Regardless of methodology, all laboratory tests have one thing in common: None of them is perfect.
Every assay has a different level of reliability. When screening for a disease such as COVID-19, we are particularly interested in a test’s sensitivity (that is, it’s ability to detect disease); we’d love such a screening test to be 100% sensitive and thereby not miss a single case. In truth, no test’s sensitivity is 100%, and in this particular case even the best assays only score around 98%. This means that out of every 100 patients with COVID-19 who are evaluated, two might test negative for the virus. In a pandemic this can have dire consequences, so health care providers – unable to fully trust their instruments – must employ clinical acumen and years of experience to navigate these cloudy skies. We are hopeful that additional tools will complement our current methods, but with new assays also come new questions.
Is anyone safe?
We receive regular questions from physicians about the value of antibody testing, but it’s not yet clear how best to respond. While the assays seem to be reliable, the utility of the results are still ill defined. Antibodies to SARS-CoV-2 (both IgG and IgM) appear to peak about 2-3 weeks after symptom onset, but we don’t yet know if the presence of those antibodies confers long-term immunity. Therefore, patients should not use the information to change their masking or social-distancing practices, nor should they presume that they are safe from becoming reinfected with COVID-19. While new research looks promising, there are still too many unknowns to be able to confidently reassure providers or patients of the true value of antibody testing. This underscores our final point: Medicine remains an art.
As we are regularly reminded, we’ll never fully anticipate the challenges or barriers to success, and technology will never replace the value of clinical judgment and human experience. While the situation is unsettling in many ways, we are reassured and encouraged by the role we still get to play in keeping our patients healthy in this health care crisis, and we’ll continue to do so through whatever the future holds.
Dr. Notte is a family physician and chief medical officer of Abington Lansdale (Pa.) Hospital – Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
