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Cassie and Len Calabrese’s COVID-19 Corner: Issue #5

Cassie and Len Calabrese’s COVID-19 Corner: Issue #5

This week in addition to our ‘picks’, I want to remind all United Rheumatology members to feel free to reach out to me or Cassie (or both) for challenging issues that COVID may have brought to your practice or your lives that we may be able to assist you with. We clearly don’t have all the answers but are happy to informally engage with you on such issues and to provide as much help as possible. Feel free to contact us, you will find our emails at the bottom of the article. Just click on our names for the e-mail link.

Len’s Pick

This week marked the 2020 virtual EULAR meeting which just ended. Overall I thought it went well especially considering they only had a few months to re-configure. This gives me even higher hopes for ACR! 

There were two major sessions on COVID and I am just waiting for all of the Saturday AM session to be posted, especially that of the presentation of our friend and collaborator Xavier Mariette’s opening talk. More on that next week.

Concurrent with EULAR COVID events was the publication of the EULAR Provisional recommendations on the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2 presented by Robert Landewe (Read Healio Rheumatology ‘Flying blindly:’ EULAR offers recommendations for COVID-19- for a brief summary https://www.healio.com/news/rheumatology/20200604/flying-blindly-eular-offers-recommendations-for-covid19 ).

Overall these recommendations are intended to be living and breathing documents just as much as the ACR’s and are humble in their emphasis on the lack of data to drive most. They, like the ACR guidelines, represent largely ‘C’ level data at best. Still they are useful and they match up pretty closely.

I would say that two of the 13 recommendations deserve comment.

First is #7:

Patients with RMD without COVID-19 symptoms who have been in contact with a SARS-Cov-2 positive person should be tested for COVID-19 themselves. 

In my opinion this is not always practical or wise. Consider first what is ‘contact’? Our CDC defines a high risk exposure in varying ways, but 15 minutes at less than 2 meters is good rule of thumb and shorter time for face to face. Those individuals are instructed to:

“Stay home until 14 days after last exposure and maintain social distance (at least 6 feet) from others at all times; Self-monitor for symptoms; Check temperature twice a day; Watch for fever, cough, or shortness of breath, or other symptoms of COVID-19; Avoid contact with people at higher risk for severe illness from COVID-19”

So the real question is whether getting tested will add or detract from this? A recent editorial in the NEJM (Woloshin S False Negative Tests for SARS-Cov-2 Infection Challenges and implications on line June 5, 2020) notes that most diagnostic tests may be only 70% sensitive and thus are poor tools for decision-making a good percentage of the time.  Accordingly we believe that for most with truly high risk exposures, counsel should be to self-quarantine and be monitored as above. Unfortunately it’s not always a perfect world.

The other recommendation that deviates a bit from the ACR guidance document surrounds a patient on immune based therapies that develops COVID-19.

ACR says:

HCQ/CQ, SSZ, and NSAIDs may be continued.  Moderate to high Immunosuppressants (e.g., tacrolimus, CSA, MMF, AZA), non–IL- 6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test result for COVID- 19. The panel noted uncertainty re: temporarily stopping MTX or LEF in this situation.

EULAR says:

If patients with RMD experience mild symptoms of COVID-19, potential treatment changes in DMARDs should be discussed on a case-by-case basis.

First note there was a lot of excellent discussion and internal disagreement that contributed to these statements but overall I (Cassie too) favor the EUALR approach. It’s less prescriptive and humble. In fact, about the only thing I know I would do (and have done), was to tell my patients in such settings to stop methotrexate until the dust settles. I do this because the first week after SARS CoV-2 exposure is critical for generating an adaptive immune response which is essential for recovery. Furthermore, we know methotrexate is more inhibitory than any biologic (save rituximab) in inhibiting antibody response to T-cell dependent and T-cell independent antigenic challenges. The rest of these decisions are all on the table so to speak. For example, in an RA patient with non-erosive disease and in deep remission I may tell him/her to stop everything and wait it out and to see infection evolves. In another patient with poorly controlled and highly symptomatic disease on a biologic (TNFi, IL-6i especially), I may stop methotrexate and continue biologic. That is shared and informed decision making. As for hydroxychloroquine, I would continue it but my hopes are fading fast that it offers anything at all. 

Cassie’s Pick

Another hot topic in the COVID-19 news explosion from last week is the hydroxychloroquine study drama. Two papers related to COVID-19 published in well-respected journals were retracted on June 4. Both studies, one was a large study published in The Lancet showing an increased risk of mortality and cardiac arrhythmia associated with hydroxychloroquine use in hospitalized COVID-19 patients (https://www.medpagetoday.com/infectiousdisease/covid19/86642), and the other was published in New England Journal of Medicine, demonstrating that underlying cardiovascular disease is associated with an increased risk of mortality in hospitalized COVID-19 patients, and found no association between ACE inhibitor or ARB use and in-hospital death in these patients (https://www.nejm.org/doi/full/10.1056/NEJMoa2007621).

These studies were both retracted because they used a data collection company called Surgisphere that claimed to store de-identified electronic healthcare data from 1,200 healthcare organizations across > 40 countries. After numerous concerns were raised about the study populations, as well as the authenticity of the data, the study authors voiced that they could no longer vouch for the data’s accuracy and the studies have been retracted. Fallout continues this week in the firing of a co-author who introduced the lead author to the Surgisphere database (see Medpagetoday.com coverage for more – https://www.medpagetoday.com/infectiousdisease/covid19/86933?xid=nl_popmed_2020-06-08&eun=g1069432d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=CoronaBreak_060820&utm_term=NL_Daily_Breaking_News_Active)

Despite these theatrics, we wonder where does this leave the role of hydroxychloroquine in the treatment of COVID-19 – is there one? I think given the data we have so far, we have yet to see any convincing evidence suggesting a role for hydroxychloroquine, but we will stay tuned.

Also hot off the press this week, the WHO has now joined CDC in their masking recommendations, stating that everyone should wear cloth masks in public (https://www.who.int/publications/i/item/advice-on-the-use-of-masks-in-the-community-during-home-care-and-in-healthcare-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak), but we can talk about masks another day…

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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