Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. It is a high-mortality syndrome that is widespread globally. In this review, we explore the evolving understanding of the immunological features of sepsis, emphasizing the simultaneous occurrence of pro-inflammatory and anti-inflammatory responses during the disease progression. Early in the disease course, the host is typically in a pro-inflammatory state, characterized by excessive inflammatory responses and vascular damage. As the disease progresses, the host tends toward an immunosuppressive state, marked by immune suppression and secondary infections. This article outlines the immunological characteristics of these two states, including the reciprocal promotion of inflammatory storms and coagulation abnormalities, as well as the death and depletion of immune cells. The heterogeneity of sepsis presents a significant challenge to targeted therapy. A key future direction in sepsis immunology diagnosis and treatment is distinguishing endotypes among sepsis patients, identifying the immunological features and pathogenic mechanisms of each endotype, and enabling focused therapeutic interventions targeting specific sepsis endotypes.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. It is a high-mortality syndrome that is widespread globally. In this review, we explore the evolving understanding of the immunological features of sepsis, emphasizing the simultaneous occurrence of pro-inflammatory and anti-inflammatory responses during the disease progression. Early in the disease course, the host is typically in a pro-inflammatory state, characterized by excessive inflammatory responses and vascular damage. As the disease progresses, the host tends toward an immunosuppressive state, marked by immune suppression and secondary infections. This article outlines the immunological characteristics of these two states, including the reciprocal promotion of inflammatory storms and coagulation abnormalities, as well as the death and depletion of immune cells. The heterogeneity of sepsis presents a significant challenge to targeted therapy. A key future direction in sepsis immunology diagnosis and treatment is distinguishing endotypes among sepsis patients, identifying the immunological features and pathogenic mechanisms of each endotype, and enabling focused therapeutic interventions targeting specific sepsis endotypes.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy* ; Humans ; SARS-CoV-2 ; Treatment Outcome