Date of this Version
Nature Immunology, VOL 21, October 2020, 1146–1151 https://doi.org/10.1038/s41590-020-0779-1
The role of cytokines in COVID-19” online symposium was presented on 18 June 2020 by the NIH/FDA Immunology and Cytokine Interest Groups and was purposed to discuss our rapidly changing understanding of COVID-19-related cytokine responses in different stages of infection, including the etiologies, downstream consequences and possible mitigation strategies.
The symposium was opened by Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health (NIAID, NIH), and Janet Woodcock, Director of the Center of Drug Evaluation and Research, Food and Drug Administration (CDER, FDA) and currently leading the therapeutics component of Operation Warp Speed. Fauci briefly reviewed the current status of the coronavirus disease 2019 (COVID-19) pandemic, noting that the worldwide incidence had grown to 8 million cases and more than 300,000 deaths, with >120,000 fatalities in the USA alone (incidence on June 18 2020). The causative virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a single-stranded RNA virus that uses angiotensin-converting enzyme 2 (ACE2) as a cellular receptor. The atomic-level conformation of the prefusion spike protein of the virus was recently described by NIAID Vaccine Research Center scientists and colleagues1. He also underscored the role of cytokines in the pathogenesis of the different clinical presentations of COVID-19, ranging from asymptomatic to pneumonia, neurological disorders, acute respiratory distress syndrome (ARDS), cardiomyopathies, sepsis, hypercoagulability, multiorgan failure and death, as well as the multisystem inflammatory syndrome seen in children. Also, the benefit of dexamethasone treatment in severe COVID- 19 cases requiring ventilation was discussed, which is consistent with the central roles of inflammation and a cytokine storm in causing serious pathology. Fauci ended his talk by calling attention to the multiple initiatives undertaken and supported by the NIAID to address the COVID-19 outbreak. Woodcock followed with an address that underscored the broad variety of clinical presentations of COVID-19, thus highlighting the central role of the immune response in this disease. She also remarked on the apparent geographic clusters of disease manifestations and the need to better understand possible factors in host–pathogen interactions beyond those health conditions already identified, such as prior innate immune experience and subtle differences in ACE2 expression in the populations. Lastly, she discussed the complexity of the data emerging from the multiple clinical trials that are targeting the inflammatory process underlying the disease, emphasizing the importance of establishing clinically relevant biomarkers to guide the therapeutic course.