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Rationale for Evaluating PDE4 Inhibition for Mitigating against Severe Inflammation in COVID-19 Pneumonia and Beyond.
Bridgewood, Charlie; Damiani, Giovanni; Sharif, Kassem; Watad, Abdulla; Bragazzi, Nicola L; Quartuccio, Luca; Savic, Sinisa; McGonagle, Dennis.
  • Bridgewood C; Department of Musculoskeletal Disease, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
  • Damiani G; Department of Clinical Dermatology, IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
  • Sharif K; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
  • Watad A; Department of Musculoskeletal Disease, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
  • Bragazzi NL; Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel.
  • Quartuccio L; Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel.
  • Savic S; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
  • McGonagle D; Department of Health Sciences (DISSAL), School of Public Health, University of Genoa, Genoa, Italy.
Isr Med Assoc J ; 22(6): 335-339, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-607449
ABSTRACT

BACKGROUND:

In the absence of definitive anti-viral therapy, there is considerable interest in mitigating against severe inflammatory reactions in coronavirus disease-2019 (COVID-19) pneumonia to improve survival. These reactions are sometimes termed cytokine storm. PDE4 inhibitors (PDE4i) have anti-inflammatory properties with approved indications in inflammatory skin and joint diseases as well as chronic obstructive pulmonary disease (COPD). Furthermore, multiple animal models demonstrate strong anti-inflammatory effects of PDE4i in respiratory models of viral and bacterial infection and also after chemically mediated lung injury. The rationale for PDE4i use in COVID-19 patients comes from the multimodal mechanism of action with cytokine, chemokine, and other key pathway inhibition all achieved with an excellent safety profile. We highlight how PDE4i could be an overlooked treatment from the rheumatologic and respiratory armamentarium, which has potential beneficial immune-modulation for treating severe COVID-19 pneumonia associated with cytokine storms. The proposed use of PDE4i is also supported by age-related immune changes in inflammation severity in PDE4i modifiable pathways in primate coronavirus disease. In conclusion, over-exuberant anti-viral immune responses in older patients with COVID-19 may pose a substantial risk to patient survival and mitigation against such hyper-inflammation with PDE4i, especially with anti-viral agents, is a strategy that need to be pursed, especially in older patients.
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Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Disease Outbreaks / Coronavirus Infections / Communicable Diseases, Emerging / Phosphodiesterase 4 Inhibitors / Anti-Inflammatory Agents Type of study: Diagnostic study / Experimental Studies / Observational study / Prognostic study Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Isr Med Assoc J Journal subject: Medicine Year: 2020 Document Type: Article Affiliation country: United kingdom

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Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Disease Outbreaks / Coronavirus Infections / Communicable Diseases, Emerging / Phosphodiesterase 4 Inhibitors / Anti-Inflammatory Agents Type of study: Diagnostic study / Experimental Studies / Observational study / Prognostic study Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Isr Med Assoc J Journal subject: Medicine Year: 2020 Document Type: Article Affiliation country: United kingdom