Issue: January 2022
Disclosures: Calabrese reports consulting relationships with AbbVie, Centecor Biopharmaceutical, Crescendo Bioscience, GlaxoSmithKline, Horizon Pharma, Janssen Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals and UCB.
January 25, 2022
4 min read

COVID-19, epistemic chaos and rheumatology: How can we critically appraise the science?

Issue: January 2022
Disclosures: Calabrese reports consulting relationships with AbbVie, Centecor Biopharmaceutical, Crescendo Bioscience, GlaxoSmithKline, Horizon Pharma, Janssen Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals and UCB.
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As we now enter the third year of COVID-19 and reflect, we should begin by asking ourselves: Just how good are we doing in critically appraising and utilizing the emerging science of this new field?

As you all recognize, this is a completely different and totally unique situation surrounding this disease, the likes of which are unprecedented in biomedical science. As Cassandra Calabrese, DO, often says, keeping up with this literature makes her feel like she is “trying to drink from an open fire hydrant.” We have both been regularly tracking the literature from all sources such as PubMed and medRxiv, and, of course, the gray literature (social media sources, such as Google and Twitter). All play important roles in information dissemination, and we have all come to recognize that we rely more on social media for the fastest breaking news in the field.

Leonard H. Calabrese, DO
Leonard H. Calabrese

Think of the first several weeks of omicron, as virtually nothing substantial hit the scientific literature in the first 3 to 4 weeks, yet an endless stream of “information” was bantered about social media regarding the possible effectiveness of emerging antivirals and the sensitivity of omicron to our monoclonals. This gathering of scientific data by press release from the companies who make products is somewhat disarming. On the other hand, I learned a lot from shout-outs on Twitter from some of the most brilliant immunovirologists on the planet who took the time to share their takes. Who would have imagined that this is now considered standard in the dissemination and appraisal of evidence?

As a result of this new system of scientific information dissemination, we frequently lack confidence that we are getting the right information in a timely fashion, as well as in our capacity to interpret it. The public is even worse off, leaving them often confused as to what is fact or fantasy. This has been referred to as “epistemic chaos,” which is said to occur when all of a society’s previously agreed upon sources of knowledge are undermined or challenged by a significant portion of the population so that society is left without any generally trusted institutions that can function as providers or arbiters of truth. Sound familiar?

In terms of sheer scale, this tsunami of data is unfathomable. As of the beginning of January, there are more than 225,000 publications cited in PubMed — all within the span of 2 years! This is all the more amazing when one considers that PubMed, which curates articles thoroughly from 1966 and selectively since the 19th century, currently lists for rheumatoid arthritis, a disease which achieved nosologic classification in the late 19th century and a disorder I have been studying for over 40 years, with 149,000 publications in the same data base! It is also worth noting that in the gray literature, Google alone has nearly 5 billion citations on COVID-19.

Thus COVID-19 represents a field where the pace of scientific publication is unprecedented and, in my opinion, feels irreconcilable with our capacity to appraise it and apply it to the care of our patients. A recent commentary in Nature from Julian H. Elliott and colleagues elegantly outlines the problem and offers some possible solutions for using this data in real time, which incorporate advances in information technology such machine learning, crowd sourcing and a variety of new programs designed to accelerate guideline production.

These authors note that “science does not stand still” and urge us not to stand still in our synthesis and translation of it into action. Just think about the halcyon pace of American College of Rheumatology guidelines for RA management (two in only 7 years) and compare that to the rapid-fire ACR COVID-19 guidelines, now in their fifth iteration in fewer than 2 years.

For rheumatologists, COVID-19 cannot be an annual grand rounds type of disease. It must be continuously monitored and appraised from all perspectives. One tool I offer is Healio’s new Unmasking COVID-19 Town Hall webinar and podcast hosted by University of Pennsylvania’s Joel Gelfand, MD, MSCE, and myself. These podcasts, occurring every few weeks, are making every effort to cover the fast-paced changes in COVID-19 from the perspective of multiple specialties, by interviewing leaders in the field (including Emory University’s Carlos del Rio, PhD, and Harvard University’s Paul Sax, MD).

You will also be hearing about a monthly series from the RJ Fasenmyer Center of Clinical Immunology at Cleveland Clinic, entitled the “COVID-19 Visiting Professor Series,” where once or twice per month on Mondays at noon, we will host an academic leader conducting cutting-edge work on some aspect of COVID of interest to rheumatologists and other practitioners treating IMIDs. It will be virtual and free, so stay tuned. Finally, we are announcing our forthcoming CME event scheduled for Saturday, Feb. 26 which will be completely dedicated to the intersection of Immune Mediated Inflammatory Diseases and COVID-19; again, this event will be both virtual and free, but space is limited and filling up fast. Please join us.

As they say, “the future is hard to predict” but I guarantee that COVID-19 will be with us for a long time, and we all need to develop some sort of system whereby we learn what we need to know to care for our patients and ourselves. Share your own take on the rapidly changing world of COVID-19 with us at or at