Cell Research: Reveals the important role of adaptive immune disorders in the occurrence of COVID-19 severe cases of new coronary pneumonia.

The new crown infection has created a global epidemic that has had a serious impact on the work and lives of people, as well as on the global economy.
of new coronary infection is an immune response disorder.
study of changes in the immune response during infection can help to clarify the pathogenesis of COVID-19, especially in severe cases, and provide a theoretical basis for clinical treatment.
cytokine storm and lymphocytic cell decline are the two main characteristics of new coronary infection, but also the patient's adverse prognostic factors, suggesting that natural immune response and adaptive immune response play an important role in the removal of viruses and the occurrence of disease.
there has been a lot of research on cytokine storms, and clinical trials have been conducted to treat them by reducing certain cytokines.
but the role and mechanism of adaptive immune response in COVID-19 are less studied.
August 5, 2020, Sun Yat-sen University Cancer Prevention and Control Center Zhou Penghui Team, Joint Sun Yat-sen University Affiliated Fifth Hospital Huang Wei Team, Sun Yat-sen University Eye Center Wei Li Team, Zhongshan University Affiliated Third Hospital Lin Yuliang Team, Zhongshan University The research team of the Cancer Prevention and Control Center, the Xie Baosong team of Fujian Provincial Hospital, and the Wei Bo team of the Second Military Medical University presented a paper entitled Dysed Force Adaptive Immune Responses to Severe COVID-19 at Cell Research.
The authors, by sequencing single-celled blood samples from COVID-19 peri-week in different courses, found that the proportion of T-effect cells and the proportion of B-effect cells in the lymphocytes of patients with severe COVID-19 occurred at the same time.
in conjunction with the results of the study that have been reported so far, that the elevated one-over-oneness of antibodies indicates a bad prognosis in patients with new coronary infections and is also an important feature of patients who die in SARS, and the authors believe that adaptive immune disorders with a severe decline in cellular immune response and abnormally elevated antibody response may be an important cause of severe illness.
the synergy between inherent immune and adaptive immune responses, viral infections can usually be eliminated in about 10 days.
some patients infected with the new coronary virus SARS-CoV-2 fail to clear the virus in time and turn it into a serious and eventual death? Since lymphocytic decline is an important feature of severe illness, the authors first counted the rate of lymphocytic decline in 284 patients of different ages, and found that the rate of lymphocytic decline increased with age, especially in older patients, of which the rate of 100% was among patients over 80 years of age.
Given the high rate of severe illness in older patients, combined with a decline in high-risk lymphocytes in older patients, the authors speculate that adaptive immune disorders may be an important cause of severe illness in older patients.
the authors' team collected 13 new crown samples (including pre-severe, severe, post-severe, post-minor and mild recovery periods) and 3 normally controlled pericular blood for single-cell sequencing by single-cell clustering The analysis found that the proportion of T-effect cells in total lymphocytes decreased strongly after both severe and severe cases, while the proportion of B-effect cells in total lymphocytes in the outer heteropathic blood of severe patients increased only once in severe cases.
T-effect cells limit the amplification and production of the virus in the body mainly by directly killing infected cells.
these cells will lead to a rapid increase in viral load at the site of infection.
The significant elevation of the B-effect cells that occur at this time produces a large number of antibodies that bind to the virus and, through the Fc segment of the antibody, binds to the Fc receptors of the natural immune cells, mediating the virus directly into the natural immune cells, a process we commonly refer to as antibody dependent enhancement.
ADE can have two serious consequences: 1) it further promotes the production of inflammatory factors, because natural immune cells such as macrophages are very sensitive to viruses, which produce a large number of cytokines when they enter cells, and 2) when viruses enter natural immune cells, they reduce their ability to devour the virus, leading to the collapse of the natural immune system.
team then looked at why T-effect cells decline rapidly in severe cases.
they looked at the changes in the different courses of COVID-19 by further grouping CD8 T cells.
found that a group of stem cell-like memory cells (Tm-2) did not decline throughout the process, but increased significantly in severe cases.
then analyzed the gene differences between these cells and CD8-effect cells and found that the cells had a unique expression line line and highly expressed the pre-thymus gene PTMA for thymus peptide a1 (Ta1).
Ta1 was involved in the development and differentiation of T lymphocytes and showed better efficacy in severe infections such as sepsis, the authors speculate that Ta1 may have protected this group of memory cells.
subsequent in vitro functional validation found that Ta1 treatment reduced the activation intensity of T cells, but did not affect the overall activation of T cells, and significantly increased the number of T-effect cells.
preliminary clinical observation data from Firesun Mountain Hospital confirmed the protective effect of Ta1 on T-cells, and the lymphocytic cell count increased significantly in severe patients after 1 week of treatment with Ta1.
these results show that in patients with normal immune system infection, the inherent immune response and adaptive immune response can work together to effectively remove the infection of the new corona virus.
But in older patients and patients with underlying diseases, the disordered adaptive immune response may develop into a severe disease by inducing the occurrence of ADE, mediating the inactivity of the inherent immune response, leading to a complete collapse of the entire immune system, loss of control of the virus, and various opportmunic infections and complications.
therefore, the authors believe that early adjustment and intervention of adaptive immune response is an important means to prevent severe diseases.
Because Ta1 reduces the overactivation of T-cells and protects T-effect cells, early monitoring of T-effect cell changes in patients with new crowns, and Ta1 therapy in patients with lymphocytes that have decreased, will likely protect the T-cell immune response and prevent the occurrence of severe diseases.
the same time, patients with severe decline in lymphocytes are advised to use propylene balls for intervention if there is a sudden increase in antibody titration.
because the main component of the C ball is IgG, it can bind to the Fc receptensor to block the occurrence of ADE.
and there have been reports that propylene ball has a better therapeutic effect on patients with severe illness.
experts commented on Ye Lilin (Professor, Institute of Immunology, Army Medical University) as follows: Cytokine storms and lymphocytes decline are two important characteristics of COVID-19 severe patients (1), suggesting that COVID-19 severe patients have inherent immune and adaptive immune disorders.
considering the critical role of adaptive immune responses in virus removal, cytokine storms may not be the main cause of COVID-19.
the therapeutic effect of immunosuppressant glucostrogen is also highly controversial.
coVID-19 patients with the majority of patients with lymphocytes and eosinophils decline, the use of glucoder hormones will only cause them to further decline, seriously impairing the adaptive immune response.
therefore, it is of great significance to study the role of adaptive immune response in the development of COVID-19 severe disease.
The authors used single-cell sequencing techniques to analyze blood samples from different courses of COVID-19, analyzing the dynamic changes of immune cells, especially lymphocytes, at different times of the disease, and the main findings of this work found that: 1) in severe patients in the cellular immune response serious decline at the same time, there was an abnormal increase in the body fluid immune response, suggesting that ADE may have accelerated the occurrence of severe disease.
This is consistent with clinical observations that the condition of many seriously ill patients does not deteriorate gradually, but rather that the sudden and rapid progression to critical illness is consistent with the fact that ADE may be the driving force behind the rapid progression of severe illness."
, in SARS, it was also observed that patients who died usually had a rapid rise in the mediuming of antibodies, and then a similar trend of rapid decline.
, it has also been found in COVID-19 that elevated levels of one-pass antibody titrity are associated with poor prognosticity in patients.
these results suggest that in the absence of a T-cell-mediated cellular immune response, a high antibody response may have contributed to the infection of natural immune cells by ADE, thereby worsening the disease; CD4-effect T cells disappear earlier than CD8-effect T cells.
CD4 T cells, CD8 T cell response, antibody quality, and natural immune response are affected; The high expression of Ta1's pregenital gene PTMA in a class of stem cell-like memory T cells accumulated in severe cases may protect this group of cells, and 4) Ta1 treatment improves lymphocyte levels in severely ill patients.
of this work lies in the fact that adaptive immune disorders are a major cause of progression in severe diseases.
Although a large number of clinical observations have reported a significant decrease in lymphocytes in COVID-19 patients, especially in severely ill patients with a significant decline in CD4 plus and CD8 plus T cells, and an increase in antibody response in severely ill patients has been observed, the immunological response and results behind these phenomena have not been explored and explained.
Based on the overall applicability immune response, the author analyzes the dynamic changes of T and B-effect cells comprehensively, revealing that ADE may be an important factor in promoting severe illness, and providing a reasonable explanation for the rapid progression of COVID-19 patients found clinically.
based on the results of the study, the authors suggest that T alpha1 and propylene balls are important means of preventing severe diseases, so this work is also very important for clinical treatment.
In addition, although T-alpha1 as an immuno-response regulator has been clinically used to treat severe sepsis and other infections, has also been applied to the treatment of new coronary severe diseases, and observed a good therapeutic effect, but the mechanism of T-alpha1 mechanism is still unclear.
The authors found that ta1's pre-body gene PTMA was highly expressed in a group of stem cell-like CD8 memory T cells that significantly increased in severe cases, speculated that Ta1 may have protected T-effect cells in viral infections, and found in T-cell in vitro activation experiments that Ta1 protected T-cells from overactivation and increased the number of effect T-cells, clarifying the cytological mechanism of T-alpha1.
future study of the molecular mechanisms of T alpha1 will contribute to a better understanding of the effects of T alpha1 on immune cells and its role in disease treatment.
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