Effective treatment of severe COVID-19 patients with tocilizumab

By Xiaoling Xu, Mingfeng Han, Tiantian Li, Wei Sun, Dongsheng Wang, Binqing Fu, Yonggang Zhou, Xiaohu Zheng, Yun Yang, Xiuyong Li and 3 more. Proceedings of the National Academy of Sciences of the United States of America, 2020

2,515 citations recorded by the source corpus.

Significance In patients with coronavirus disease 2019, a large number of T lymphocytes and mononuclear macrophages are activated, producing cytokines such as interleukin-6 (IL-6), which bind to the IL-6 receptor on the target cells, causing the cytokine storm and severe inflammatory responses in lungs and other tissues and organs. Tocilizumab, as a recombinant humanized anti-human IL-6 receptor monoclonal antibody, can bind to the IL-6 receptor with high affinity, thus preventing IL-6 itself from binding to its receptor, rendering it incapable of immune damage to target cells, and alleviating the inflammatory responses. After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

Subfields: Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/709c9b089e04dcc21f59bcd7c0ed0102447b4855

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. L. Garcia
2. Bo Huang
3. V. Cheng
4. Youhai H. Chen
5. X. Wan
6. Jinyan Liu
7. Zhixin Zhang
8. Yi Zhang

In Neurology

1. L. Garcia
2. Bo Huang
3. Youhai H. Chen
4. X. Wan
5. Jinyan Liu
6. Zhixin Zhang
7. Yi Zhang
8. Shasha Liu

Citations in the corpus

• Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies (2020, background): “Another retrospective study (56) demonstrated that TCZ showed a quick control of severe COVID-19 manifestation, such as fever, respiratory function.”
• Immune Response, Inflammation, and the Clinical Spectrum of COVID-19 (2020, positive): “(113) reported very promising results using Tocilizumab treatment in 20 patients with severe COVID-19; all patients improved remarkably within a few days and all were discharged from the ICU within an average of 15 days.”
• Interleukin‐6 in Covid‐19: A systematic review and meta‐analysis (2020, methodology): “In cohort studies assessing inflammatory response in COVID-19, risk of bias was assessed via the QUIPS tool.”
• Individuals with obesity and COVID‐19: A global perspective on the epidemiology and biological relationships (2020, background): “Preliminary data suggest tocilizumab treatment can reduce fever and oxygen requirement.(160) However, subjects with obesity with chronically elevated IL-6 may not benefit”
• The cytokine storm and COVID‐19 (2020, background): “Xu et al.(62) found that out of 21 patients with severe COVID-19, 90% recovered after a few days of treatment with TCZ.”
• COVID-19 is, in the end, an endothelial disease (2020, result): “have also shown signs of benefit in some but not all preliminary studies, although this as well as other anticytokine therapies may entail an increased risk of superinfection.(59,60) Other anti-IL-6 strategies also warrant consideration.”
• Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach (2020, neutral): “During recent months, as the severity of COVID-19 elevates globally, it has been used as an alternative treatment strategy for COVID-19 patients [129].”
• Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 (2022, background): “reported no serious adverse events [31].”