Major advances in “inflammatory storm” study of Csta’s new coronal pneumonia: Effective blocking drugs found

Recently, there have been media reports, the new coronary pneumonia infected people appear in the body “inflammatory storm.” In response to this question, on February 15th, at a press conference of the State Council’s Joint Defense and Control Mechanism, Vice-Secretary-General of the Chinese Academy of Sciences, Academician Zhou Qi, made an authoritative interpretation, including the mechanism of “inflammatory storm” and the current progress of research.

“Researchers are sifting through some of the older drugs to suppress the emergence of inflammatory factors, including some drugs that have been shown to be effective in areas such as rheumatism,” Zhou said. There are some pre-proven drugs that have been partially tested for cell levels. “

“The First Hospital affiliated with the China University of Science and Technology has done 14 cases of critically and critically ill patients, the oldest of which is 82 years old, and the results of these cases are encouraging. A multicenter randomized controlled trial is now under way, and about 100 patients will be enrolled in the group. “

After the meeting, the relevant research progress of China University of Science and Technology has aroused widespread concern, China University of Science and Technology today also issued a special briefing on the war “epidemic”, a detailed interpretation of the new coronary pneumonia “inflammatory storm” research made some important progress. Here’s an excerpt sorted out below, for everyone.

According to reports, after the outbreak of new coronal pneumonia, the research team of China University of Science and Technology set the results of many years of basic research in the field of immunology, combined with the clinical practice of the Chinese University of Science and Technology attached to a hospital, the laboratory moved forward and carried out a large number of basic research.

It is found that leukocyte interleukin-6 (IL-6) is an important pathway to induce inflammatory storms, and on the basis of the initial understanding of the mechanism, the initial clinical results have been obtained, and further multicenter clinical trials are under way.

Inflammatory Storms: Vital Killers of Life-Threatening Lives

The new coronavirus infection patients and the 2003 SARS virus is different, some patients early onset is not very dangerous, or even mild symptoms, but suddenly there will be an acceleration, the patient quickly into a state of multi-organ failure, the reason is that the patient’s body may be activated inflammatory storm.

Inflammatory storms, or cytokine storms, are overactivated by the immune system caused by infections, drugs, or certain diseases, which can quickly cause single or multi-organ failure and ultimately life-threatening.

Cytokine storms are important causes of death in SARS, MERS and influenza, and cytokine storms are also important causes of death in many patients in this outbreak.

Cytokines mainly include interferon (IFN), leukocyte interleukin (IL), chemokines), concentration stimulation factor (CSFs), tumor necrosis factor (TNF) and so on.

These cytokines are secreted by certain immune cells, some of which promote inflammation, some of which inhibit inflammation, and maintain a balance in the normal body.

Pro-inflammatory factors activate and recruit other immune cells, which secrete more cytokines and activate and recruit more immune cells, thus forming a positive feedback loop.

When the immune system is overactivated by infections, drugs, autoimmune diseases and other factors, it may secrete a large number of pro-inflammatory factors leading to positive feedback loops, breaking through a certain threshold and over-amplified, resulting in cytokine storms.

There is also a clearer understanding of the mechanism by which the new coronavirus induces an inflammatory storm.

After the new coronavirus infects the human body, it can enter the cells through angiotensin-converting enzyme 2 (ACE2), so high-expression ACE2 and direct contact with the outside world’s lung tissue has become the main target of the new coronavirus invasion.

The immune cells of the lungs are overactivated, producing a large number of inflammatory factors that form an inflammatory storm through the mechanism of positive feedback cycles. Large amounts of immune cells and tissuefluids gather in the lungs, blocking the exchange of gas between the alveoli and capillaries, leading to acute respiratory distress syndrome.

Once a cytokine storm is formed, the immune system will kill a large number of normal cells of the lungs while killing the virus, seriously damaging the lung’s ventilation function, in the lung CT as a large white, that is, “white lung”, the patient will respiratory failure, until the death of hypoxia.

At the same time, ACE2 is also highly expressed in the human body in vascular endothelial cells, heart, kidneys, liver, digestive tract and other tissue organs, all expression ACE2 tissue organs may be a new coronavirus and immune cell battlefield, eventually leading to multi-organ failure, life-threatening.

Therefore, the discovery of the new coronavirus infection induced inflammatory storm of the key cytokines, blocking its signaling, will greatly reduce the inflammatory response to the patient’s lung tissue and multi-organ damage.

Leuketointerin 6 (IL-6): an important pathway for inducing inflammatory storms

After the outbreak of new coronal pneumonia, through anhui Province, China University of Science and Technology emergency project support, The chinese University of Science and Technology, The Department of Life Sciences and Medicine Professor Wei Haiming’s team moved the laboratory to an attached hospital infection area, with the Chinese University of Science and Technology Attached First Hospital, respiratory medicine physician Professor Xu Xiaoling’s team to carry out joint research.

The research team’s comprehensive analysis of 30 immunological indicators in the blood of 33 patients with new coronary pneumonia found the key mechanism of the inflammatory storm of severe pneumonia caused by the new coronavirus infection: after the new coronavirus infection, the pathogenic T cells were quickly activated, and factors such as granulocyte-macrophages set-up stimulus factors GM-CSF and leukocynosin 6 were found.

GM-CSF further activates CD14-CD16-plus inflammatory mononucleosis, producing a larger amount of leukocylic 6 and other inflammatory factors, resulting in an inflammatory storm that leads to severe immune damage to the lungs and other organs.

Therefore, leukin 6 and GM-CSF are two key inflammatory factors in the inflammatory storm that triggers new coronary pneumonia patients.

In the “Notice on the Issuance of the New Coronary Virus Pneumonia Heavy, Critical Case Series (Trial Second Edition) for Severe and Critical Cases Of New Coronary Virus Pneumonia (Trial 2nd Edition) issued jointly by the General Office of the National Health and Health Commission and the Office of the State Administration of Traditional Chinese Medicine on February 14th, the clinical warning indicator of the deterioration of the disease has been clearly adopted as the upward trend of leukin 6.

“Tozhu monoantigen”: effective drug to block inflammatory storm of new coronary pneumonia

Based on the team’s exploration of the key mechanisms of the inflammatory storm of severe pneumonia caused by the new coronavirus infection, the team speculated that the mono-anti-Ino-resistant drug anti-IL-6 receptor, “tozhu monoantigen”, could block the inflammatory storm of new coronary pneumonia, and quickly developed a new treatment plan for “tocoad monoantigens and conventional treatments”.

Tozhu mono-resistance, the commodity name Yamelo, is a heavy anti-inflammatory drug owned by Swiss pharmaceutical giant Roche, the world’s first recombinant humanized monoclonal antibody for IL-6 receptors, is the treatment of IL-6 elevated autoimmune diseases (such as rheumatoid arthritis) first-line drugs.

In line with the principle of treating and saving people as soon as possible, the joint research team immediately launched a clinical study, the research work strictly follows the medical ethics norms, after determining the patient’s informed consent, in accordance with the new treatment program to carry out clinical trials.

The results of the first phase of the study largely validate the team’s interpretation of the mechanisms that induce inflammatory storms.

The first phase of clinical study involved 14 patients with new coronary pneumonia, the maximum age of 82 years old, 12 cases of men and 2 cases of women, including 9 cases of severe illness, 2 cases of critical condition, before treatment, there were two pulmonary diffuse lesions, of which 11 cases of persistent fever.

After the treatment of the new treatment plan of “Tozhu mono-resistance plus routine treatment”, the body temperature of 11 fever patients fell to normal within 24 hours, stable, up to 9 days, respiratory oxygenation index has improved to varying degrees, 4 patients with pulmonary CT lesions absorption improved, 1 patient with critical trachea intubation has been successfully offline.

Available clinical data suggest that this new treatment is likely to reduce mortality by blocking inflammatory storms and thus preventing patients from transitioning to critical illness and critical illness.

Expand the number of patients treated and promote multi-center clinical research

The 10 new coronary pneumonia targeted treatment hospitals in Anhui Province are accelerating the “multi-center, open and randomized controlled clinical study of the effectiveness and safety of tozhu monoantigen in the new coronavirus pneumonia”.

Currently, the multicenter research project on inflammatory storms has passed an ethical review and will be officially launched on February 6, 2020.

On February 13, according to the China Clinical Trial Registration Center, “The effectiveness and safety of tocovirus pneumonia (COVID-19) in multicenter, randomized controlled clinical studies” have been registered in clinical trials (registration number: ChiCTR20000029765).

The purpose of the study was to assess the effectiveness and safety of patients treated with common NCP (including high risk factors of severe illness) and heavy NCP.

The research team recommends that the relevant departments of the state carry out thematic research, start the national multi-center clinical research as the lead unit of the first hospital affiliated with the Chinese University of Science and Technology as the lead unit, and as soon as possible to validate the effective treatment plan into the national diagnosis and treatment plan to save more patients.

At present, five hospitals have joined the multi-center clinical research, and gradually expand to the hard-hit areas of the epidemic.

Introduction to the Research Team of the Chinese University of Science and Technology

Wei Haiming:

Professor, Ph.D. Tutor, Department of Life Sciences and Medicine, China University of Science and Technology. Executive Director of the China Immunology Society, Vice Chairman of the Professional Committee of Oncology And Biotherapy of the Chinese Immunology Society, Director of the Editorial Department of Cellular and Molecular Immunology, and Director of the Anhui Immunology Society. Mainly engaged in natural immunology research, has published SCI collection papers 145, in 2008 won the second prize of the National Natural Science, in 2007 and 2010 by the first prize of Chinese medical science and technology 1 each.

Xu Xiaoling:

Vice President of the Hospital of China University of Science and Technology, Chief of Respiratory Medicine Physician, Professor, Doctoral Mentor, Respiratory Disease Specialist, Head of Expert Group on Medical Treatment of New Coronary Virus Pneumonia in Anhui Province, Standing Member of the Respiratory Society of Anhui Medical Association, Standing Member of the Anhui Tuberculosis Society, Editorial Committee of the Journal of Clinical Lung Medicine.