Reducing mortality from 2019-nCoV: host-directed therapies should be an option

• Published in: The Lancet (British edition) Vol. 395; no. 10224; pp. e35 - e36
• Main Authors: Zumla, Alimuddin, Hui, David S, Azhar, Esam I, Memish, Ziad A, Maeurer, Markus
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 22.02.2020; Elsevier Limited
• Subjects: Betacoronavirus; Colony-stimulating factor; Coronavirus Infections - drug therapy; Coronavirus Infections - mortality; Coronavirus Infections - therapy; Coronaviruses; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Cytokines; Disease transmission; Drug Discovery; Fibrosis; Global Health; Humans; Immune response; Immunization, Passive; Immunosuppressive agents; Infections; Inflammation; Intensive care; Interferon; Interleukin 17; Leukocytes (granulocytic); Lungs; Lymphocytes T; Macrophage inflammatory protein; Macrophage inflammatory protein 1; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Pandemics; Patients; Pneumonia, Viral - therapy; Proteins; Quality of life; Respiratory distress syndrome; SARS-CoV-2; Sepsis; Tumor necrosis factor; Tumors; γ-Interferon
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(20)30305-6

All three coronaviruses induce excessive and aberrant non-effective host immune responses that are associated with severe lung pathology, leading to death.2–4 Similar to patients with SARS-CoV and MERS-CoV, some patients with 2019-nCoV develop acute respiratory distress syndrome (ARDS) with characteristic pulmonary ground glass changes on imaging. In most moribund patients, 2019-nCoV infection is also associated with a cytokine storm, which is characterised by increased plasma concentrations of interleukins 2, 7, and 10, granulocyte-colony stimulating factor, interferon-γ-inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha, and tumour necrosis factor α.2–6 In those who survive intensive care, these aberrant and excessive immune responses lead to long-term lung damage and fibrosis, causing functional disability and reduced quality of life.7,8 Specific drugs to treat 2019-nCoV will take several years to develop and evaluate. Infection with 2019-nCoV appears to be initially associated with an increased Th2 response,4 which might reflect a physiological reaction to curb overt inflammatory responses, a clinical phenomenon that guided the optimal timing of interferon treatment in patients with sepsis, resulting in increased survival.14 Interleukin 17 blockade might benefit those patients who have a 2019-nCoV infection and increased plasma concentration of interleukin 17.