Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents

Virology Journal

Sumanth Khadke¹  Nausheen Ahmed²  Molly Gallogly³  Marcos de Lima³  Nayla Ahmed⁴  Ryan Ratts⁵  Muhammad Rizwan Sohail⁶  Shine Raju⁷ 

[1] Our Lady of Fatima University, 120 MacArthur Highway, 1440, Valenzuela, Metro Manila, Philippines;Section of Hematology Oncology, Bone Marrow Transplant and Cellular Therapy, University Of Kansas Medical Center, 3901 Rainbow Blvd, 66160, Kansas City, KS, USA;Section of Hematology Oncology, Stem Cell Transplant and Cellular Therapeutics, University Hospitals Seidman Cancer Center - Case Western Reserve University, 11100 Euclid Avenue, 44106, Cleveland, OH, USA;Section of Hospital Medicine, Dartmouth-Hitchcock Medical Center - Geisel School of Medicine, One Medical Center Drive, 03766, Lebanon, NH, USA;Section of Hospital Medicine, Dartmouth-Hitchcock Medical Center - Geisel School of Medicine, One Medical Center Drive, 03766, Lebanon, NH, USA;Section of Pediatric Hospital Medicine, Dartmouth-Hitchcock Medical Center - Geisel School of Medicine, One Medical Center Drive, 03766, Lebanon, NH, USA;Section of Infectious Diseases and Cardiovascular Medicine, Mayo Clinic College of Medicine and Science, 200 1st St SW, 55905, Rochester, MN, USA;Section of Pulmonary and Critical Care, University Hospitals Cleveland Medical Center - Case Western Reserve University, 11100 Euclid Avenue, 44106, Cleveland, OH, USA;

关键词: COVID-19;    SARS-CoV-2;    Pathophysiology;    Cytokine release syndrome;    Angiotensin converting enzyme 2;    Acute respiratory distress syndrome;    Tocilizumab;    Immunotherapy;    Antiviral;    Chloroquine;   

DOI  :  10.1186/s12985-020-01415-w

来源: Springer

【 摘 要 】

BackgroundCoronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage.DiscussionWe reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions.ConclusionEvidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.

【 授权许可】

CC BY