Existing Drugs That Might Treat COVID

When describing a pathophysiological pathway and suggesting a potential drug, one might miss the big picture and overlook the effects on interrelated pathways and downstream cascades. This diagram was designed to remind clinicians and researchers of intricate interwoven pathways.

COVID is a multi-organ disease that manifests throughout the whole body. Individuals with underlying morbidities such as cardiovascular disease, hypertension, obesity, and diabetes are especially susceptible to developing severe COVID. Every promising approach must be used to help clinicians and scientists understand the precise pathophysiology of COVID so that they can develop effective treatments as soon as possible.

Three doctors at Radboud University Medical Centre Nijmegen in the Netherlands, Mathijs Binkhorst, MD, Annette K Offringa, MD, and Johannes G van der Hoeven, MD, PhD recently researched the pathophysiological mechanisms underlying COVID and existing drugs that target these pathways. Together they created a comprehensive diagram that provides a holistic view of COVID pathophysiology and an integral approach to developing targeted therapies. The diagram which they published as part of a preprint on July 7, 2020, aids in visualizing the effects of repurposed drugs on intended targets and also alerts to potential adverse effects on interacting pathways.

Our paper contains much of the same information as far as the pathophysiology of COVID-19 is concerned. The difference is that we summarized it in a single graphic instead of just describing it using text. Our idea is that 'a picture is worth a thousand words'.

Mathijs Binkhorst, MD,?Department of Neonatology, Radboud University Medical Center Amalia Children’s Hospital

Version #1

Dr. Mathijs Binkhorst initially conceptualized the idea of creating a diagram after reading hundreds of COVID related articles. One night he started mind mapping and wrote down all relevant information that he could remember. This resulted in the first version of the mind map.

Version #2

After reviewing the first draft, Dr. Binkhorst and his colleagues decided to transform the diagram into a submittable document. They read hundreds of papers and contributions identified on PubMed, medRxiv, bioRxiv, and websites. Then they selected 70 peer reviewed articles, 27 preprints, and 3 websites which were used to construct of the diagram. They reorganized the original version and added additional information. The authors also included their own speculations regarding bowel wall angioedema, ADAMTS-13 deficiency, and the therapeutic use of C1-esterase inhibitor, and incorporated them into the overview.

Final Version

The second draft was then sent to a talented medical illustrator, who, with clear instructions, created the final version of the graphic that appeared in the preprint publication. The diagram is self-explanatory, especially with the information contained in the legend.?In the submitted paper the authors concisely explain the concepts visualized in the illustration and put several pieces of the COVID puzzle together to create a first impression of the complete picture.

• It visualizes the interwovenness of pathophysiological pathways, with a focus on cytokine-induced pathology, the sequelae of ACE2 downregulation, and thrombosis associated with microvascular injury.
• It aids in overseeing the effects of repurposed drugs on intended targets, and also alerts to the adverse effects on interacting pathways.?
• It shows how underlying morbidities, such as cardiovascular disease, hypertension, obesity, diabetes, pulmonary disease, and immunocompromising conditions, are especially susceptible to severe COVID disease?
• It shows features of later stages of COVID including fever, hypoxia, respiratory failure, lymphocytopenia, and elevated levels of D-dimers, CRP, lactate, LDH, cytokines, and ferritin

Repurposing Drugs for COVID

Research suggests that there may be quite a few existing drugs that could be repurposed to treat COVID. In a recent NIH-funded study, researchers screened a chemical library that contained nearly 12,000 existing drug compounds for their potential activity against SARS-CoV-2. Of the existing drugs screened, 21 showed potential to treat COVID. Multiple studies are currently underway testing promising drugs. In studies, some repurposed drugs have reduced the number of SARS-CoV-2 infected cells from 65- 85%. Timing is important when using repurposed drugs. Some scientists believe that the best current option to treat COVID is using hydroxychloroquine early in disease progression. There are over 100 registered studies around the world testing the effectiveness of hydroxychloroquine to treat COVID. Remdesivir may also be more effective in the early stages of COVID. Baricitinib may have advantageous effects in early and advanced disease.

Every promising approach must be used and as many avenues as possible must be explored to combat the virus. This excellent diagram will help clinicians and scientists understand the precise pathophysiology of COVID so that they can develop effective treatments as soon as possible.

Link to Paper & Authors

Comprehensive Synopsis of Suggested Pathophysiological Mechanisms and Repurposed Drugs.?Preprints?2020, 2020070108 (doi10.20944 / preprints202007.0108.v1)?

Mathijs Binkhorst, MD,?Department of Neonatology, Radboud University Medical Center Amalia Children’s Hospital, The Netherlands

Annette K Offringa, MD, Microbiology and System Biology, Netherlands Organisation for Applied Scientific Research, The Netherlands

Johannes G van der Hoeven, MD, PhD, Department of Intensive Care Medicine, Radboud University Medical Center, The Netherlands

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Copyright ? 2020 Margaretta Colangelo. All Rights Reserved.

This article was written by?Margaretta Colangelo.?Margaretta is a leading AI analyst based in San Francisco. She serves on the advisory board of the AI Precision Health Institute at the University of Hawai?i?Cancer Center.?

Twitter?@realmargaretta