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Cassie and Len Calabrese’s COVID-19 Corner: Issue #8

Cassie and Len Calabrese’s COVID-19 Corner: Issue #8

The New York Times Journal of Medicine

This week, given that we are now entering the dog days of summer, we focus on two stories and more importantly we take this opportunity to discuss how we in medicine are filtering, receiving, and appraising medical scientific data on COVID-19. The story is part tongue-in-cheek, but truth be told is frighteningly real. Also, as of Sunday, June 28th there are now posted on PubMed and MedRxiv and (the preprint server for health services which none of us paid attention to before COVID) over 30,000 papers! In addition, the number of studies on www.clinincaltrials.gov has grown from 904 in early April to over 2,600 as of now. With such numbers reflecting the torrid pace of biomedical ‘research’ and related commentaries, the info stream seems to be spreading faster than the disease. That is actually a feat when you are talking about a pandemic…

Aside from the awe of the sheer volume of the data one should reasonably ask how certain articles rise to the top of this pile. Since 15% are not even published it cannot be from the impact factor of the journal. Furthermore, consider that even a letter to the editor can go viral and take the world by storm. Len knows this from his experience in 1987 when he reported the first transmission of HIV (HTLV-III from a man to woman to man in the NEJM https://www.nejm.org/doi/full/10.1056/NEJM198604103141510.)  It went viral for sure but at that time it meant phone calls from around the world… (he seriously regrets this was pre-internet as he would have picked up a pile of Twitter followers).

We bring to your attention to stories from the Journal (aka NYTJM)

  1. Public policy meets the struggle for truth in the scientific literature.

On Sunday a cover story ran entitled “How the World Missed COVID-19’s Silent Spread https://www.nytimes.com/2020/06/27/world/europe/coronavirus-spread-asymptomatic.html?searchResultPosition=1 

It’s a story about how the report of an important transmission series starting with an asymptomatic carrier was published in early March in the NEJM by a German physician Comilla Rothe which should have been a serious warning shot that our notions and strategies for suppressing disease spread were going to be grossly inadequate if true.  Despite the fact that this is now known to be the most pressing issue in the pandemic it took months to establish credibility because of scientific hubris of competing investigators, deaf and confused public health agencies, and brain-dead policymakers unwilling to admit the scary news to a weary public. We believe that this suppressed the endorsement of masks which now have been shown to be the easiest and most effective intervention to slow transmission but has languished for the reasons we have recently discussed in this column. Read the piece, it is chilling.

  1. COVID-19 meets Big Data.

On Sunday morning the always perspicacious Andy Laster sent us an article on an intriguing study using Big Data to study the immunobiology of COVID19. He told us he came upon it in an article in the NYTJM!  The article, entitled “How Coronavirus Short-Circuits the Immune System” https://www.nytimes.com/2020/06/26/health/coronavirus-immune-system.html?searchResultPosition=1, is very cool and cites a handful of high impact publications exploring COVID-19 with Big Data studies, none of which are published but are available on MedRxiv.  Ironically, Len had read one of the cited studies because he knew of the strong work by one of the groups but it was more an accident than by design. A question arises – how did these articles all make it to the NYTM and what effect will their being cited have on the impact of their work? We suspect it will be considerable. Such projection of prepublication science makes us wonder that with all the fine work going on in the COVID-19 space, the ability to achieve the bully pulpit is a complex and opaque process and we need to be careful. We still rely on reviewing the major journals by email (i.e.  NEJM, Lancet, Annals, JCI, Cell, Nature Med and all Nature Reviews, for their own filtering of the current literature in each issue) and of course by the people and groups we follow on Twitter (i.e. Eric Topol, numerous professional organizations), and all the journals and many smart rheumatologists. Follow us and we will steer you right!

The articles cited in the NYJM include one from the UK and two from the US (U Penn), each applying multi-parameter interrogations of blood including advanced flow (over 200 subsets, gene expression, cytokine arrays) of course all supported by informatic programs of great complexity. The work Andy sent to us is by Adrian Haday and colleagues in London entitled “A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis” https://www.medrxiv.org/content/10.1101/2020.06.08.20125112v1. We have read the study with interest and indeed it is complex as all Big Data papers are. In a hospitalized cohort with COVID-19 and a comparison control population, they have identified several immune endotypes with features shared by a post-vaccination state as well as the state of sepsis-associated immunodeficiency. Inferences from this study suggested that strategies that have been directed at sepsis-associated immunodeficiencies such as IL-7 and anti-IP10 may hold promise in COVID-19. Such investigations have the potential to both further our understanding of immunobiology but also to move us a step closer to a more personalized medical approach. Perhaps their therapeutic suggestions are speculative but they are merely attempting to distill their message and put their work out for attention and review. Yes, we need peer review more than ever but we also need new systems of data filtering and critical appraisal so we are not swept away in the COVID storm.

Please give us a shout out with any questions!

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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

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