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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.
Virol J. 2020 Oct 15; 17(1):154.VJ

Abstract

BACKGROUND

Coronavirus 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.

DISCUSSION

We 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.

CONCLUSION

Evidence 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.

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Authors+Show Affiliations

Khadke S
Our Lady of Fatima University, 120 MacArthur Highway, 1440, Valenzuela, Metro Manila, Philippines.
Ahmed N
Section of Hospital Medicine, Dartmouth-Hitchcock Medical Center - Geisel School of Medicine, One Medical Center Drive, Lebanon, NH, 03766, USA.
Ahmed N
Section of Hematology Oncology, Bone Marrow Transplant and Cellular Therapy, University Of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA.
Ratts R
Section of Hospital Medicine, Dartmouth-Hitchcock Medical Center - Geisel School of Medicine, One Medical Center Drive, Lebanon, NH, 03766, USA. Section of Pediatric Hospital Medicine, Dartmouth-Hitchcock Medical Center - Geisel School of Medicine, One Medical Center Drive, Lebanon, NH, 03766, USA.
Raju S
Section of Pulmonary and Critical Care, University Hospitals Cleveland Medical Center - Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
Gallogly M
Section of Hematology Oncology, Stem Cell Transplant and Cellular Therapeutics, University Hospitals Seidman Cancer Center - Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
de Lima M
Section of Hematology Oncology, Stem Cell Transplant and Cellular Therapeutics, University Hospitals Seidman Cancer Center - Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
Sohail MR
Section of Infectious Diseases and Cardiovascular Medicine, Mayo Clinic College of Medicine and Science, 200 1st St SW, Rochester, MN, 55905, USA. sohailmd@mac.com.

MeSH

Antiviral AgentsBetacoronavirusCOVID-19COVID-19 TestingChildClinical Laboratory TechniquesCoronavirus InfectionsCytokinesHumansImmunity, InnatePandemicsPneumonia, ViralSARS-CoV-2Viral LoadCOVID-19 Drug Treatment

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

33059711

Citation

Khadke, Sumanth, et al. "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, vol. 17, no. 1, 2020, p. 154.
Khadke S, Ahmed N, Ahmed N, et al. 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. Virol J. 2020;17(1):154.
Khadke, S., Ahmed, N., Ahmed, N., Ratts, R., Raju, S., Gallogly, M., de Lima, M., & Sohail, M. R. (2020). 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, 17(1), 154. https://doi.org/10.1186/s12985-020-01415-w
Khadke S, et al. 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. Virol J. 2020 Oct 15;17(1):154. PubMed PMID: 33059711.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Khadke,Sumanth, AU - Ahmed,Nayla, AU - Ahmed,Nausheen, AU - Ratts,Ryan, AU - Raju,Shine, AU - Gallogly,Molly, AU - de Lima,Marcos, AU - Sohail,Muhammad Rizwan, Y1 - 2020/10/15/ PY - 2020/4/20/received PY - 2020/9/18/accepted PY - 2020/10/16/entrez PY - 2020/10/17/pubmed PY - 2020/11/6/medline KW - Acute respiratory distress syndrome KW - Angiotensin converting enzyme 2 KW - Antiviral KW - COVID-19 KW - Chloroquine KW - Cytokine release syndrome KW - Immunotherapy KW - Pathophysiology KW - SARS-CoV-2 KW - Tocilizumab SP - 154 EP - 154 JF - Virology journal JO - Virol J VL - 17 IS - 1 N2 - BACKGROUND: Coronavirus 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. DISCUSSION: We 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. CONCLUSION: Evidence 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. SN - 1743-422X UR - https://www.unboundmedicine.com/medline/citation/33059711/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_ DB - PRIME DP - Unbound Medicine ER -