Cassie and I have made allusions to Sisyphus many times in the past week who as we all know was a king who was punished for deceitfulness by being forced to roll an immense boulder up a hill only for it to roll down every time it neared the top, repeating this action for eternity. I had a manuscript accepted this week which I was then asked to revise twice in two days because of new publications impacting the topic. Cassie said just let it go because you can’t keep up with COVID-19 and she was right. As of 2:15 pm EST on June 2, 2020, there are 18,121 citations in PUBMED for COVID-19! There are an additional 3610 publications on MedRxiv, a server for preprints not yet peer-reviewed. Given the pandemic is only 5 months old I think there has been more biomedical research done (good, bad, and ugly) in COVID-19 than in the first decade of HIV disease. By years end, I know this will be even more dramatic in terms of advances in every aspect of the infection and that includes identifying better therapies and hopefully the holy grail of a candidate vaccine.
Of all the papers I read this week it is the study from France on anankinra therapy for severe COVID-19 that has me somewhat pumped.
Thomas Heut et. al: Anakinra for severe forms of COVID-19: a cohort study Published: May 29, 2020•DOI:https://doi.org/10.1016/S2665-9913(20)30164-8• https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30127-2/fulltext
While this is far from a definitive study, these investigators studied anakinra 100mg BID in 52 patients with advancing pneumonia from COVID-19, but not on a ventilator and compared them to a historical group who receive standard treatments and supportive care. The main outcome was admission to the ICU for mechanical ventilation or death. The results demonstrated that 25% in the anakinra group advanced versus 73% in the historical group. The effect size was huge and there were no significant toxicities aside from LFTs in a small percent. I could go on about the flaws of historical bias and changing care, concomitant use of other therapies in both groups including HCQ, azithromycin, and other antibiotics as well as matching challenges but those aside the results are provocative and exciting. Now the real work needs to be done which is to validate this trial in the context of a larger RCT. At the moment there are currently 1903 trails registered in COVID-19 on www.clinincaltrials.gov so if you are bored (who’s not?) surf it and you will be amazed. There are fourteen IL-1 targeting trials that I saw, including 9 with anakinra. There is a lot of interest in anakinra in particular, because of its huge therapeutic margin, short half-life and track record in other cytokine storm diseases ( for the executive summary read Randy Cron’s accompanying editorial- it’s terrific: Coronavirus is the trigger, but the immune response is deadly https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30165-X/fulltext ). Anyway, I am heading back to push that stone up the hill for a while before I go home for a Negroni.
The rheumatology community has responded rapidly to COVID-19, by forming the COVID-19 Global Rheum Alliance (https://rheum-covid.org/), an international effort with a goal to aid clinicians and researchers in real-time as the pandemic evolves, providing insights into how COVID-19 is impacting patients with rheumatic diseases. In early March 2020, the concept was developed and publicized through social media, email, listserves, and personal and professional networks. Within 2 days of the initial idea, the alliance engaged rheumatologists across the world, with support from over 200 professional and non-profit organizations, including the American College of Rheumatology, European League Against Rheumatism, British Society of Rheumatology and many others. Early descriptive data are updated frequently online and through twitter (https://mailchi.mp/a6dc80671481/just-launched-the-covid-19-global-rheumatology-registry-4810762), and there are currently almost 2000 patients included in the registry.
The publications produced so far from this data have entered the double digits and the most recent manuscript is of great interest to us. Gianfrancesco et al. report a case series of the first 600 cases of COVID-19 positive patients with rheumatic diseases, collected from March 24 to April 20, 2020. The most important takeaway is their finding that glucocorticoid (GC) use of ≥ 10 mg/day was associated with a higher risk of hospitalization due to COVID-19. Results from studies of inflammatory bowel disease patients have also reported negative outcomes associated with GC use (https://www.gastrojournal.org/article/S0016-5085(20)30655-7/fulltext). Both of these studies that the use of TNF inhibitors was not associated with poor outcomes.
We encouraged you to enter your COVID positive patients into their registry. Each patient takes 5-10 minutes and the information this is providing the rheumatology community and beyond is so valuable.
Please give us a shout out with any questions!
Leonard H. Calabrese, DO, is the head of the RJ Fasenmyer Center for Clinical Immunology and Vice-Chair of the Department of Rheumatic and Immunologic Diseases at Cleveland Clinic Dr. Calabrese has lectured nationally and internationally on the subjects of immunology, rheumatology, and viral diseases. He is the author of more than 400 published peer-reviewed articles, book chapters, and reviews. @LCalabreseDO
Cassandra Calabrese, DO, is a staff physician in the Department of Rheumatic and Immunologic Diseases and the Department of Infectious Diseases at Cleveland Clinic and directs the combined Rheumatology-Infectious Disease training program. She also directs the Clinic for immune-related adverse events form cancer immunotherapy within the department of Rheumatic and Immunologic Diseases. @CCalabreseDO