Sepsis, including viral infections, are major causes of death worldwide. Studies show that in 2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which 11 million patients died. Studies in China also showed that more than 1 million patients died of sepsis in 2015. Previous studies have suggested that sepsis are often secondary to excessive inflammatory response syndrome. However, treatment measures targeting excessive inflammatory response failed to effectively improve the prognosis of patients. PD-1 and PD-L1 are key mediators in T cell depletion in sepsis patients. Therefore, the investigators try to performe a clinical research to investigate the efficacy of PD-1 and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection.
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in
2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which
eleven million patients died. Studies in China also showed that more than one million
patients died of sepsis in 2015. Therefore, how to effectively reduce the mortality of
patients with sepsis has become a focus of clinical and basic research.
Previous studies have suggested that sepsis are often secondary to excessive inflammatory
response syndrome. However, treatment measures targeting excessive inflammatory response
failed to effectively improve the prognosis of patients. The reason is that sepsis-related
immune dysfunction can increase the risk of secondary infection and even affect the fatality
rate.
The immune checkpoint pathway is the endogenous component of the immune system, which is
responsible for checking the immune response and keeping it in a normal physiological state.
Tumor cells can evade host recognition through this pathway. One of these immunocheckpoint
pathways is the PD-1 and PD-L1 pathways. PD-1 is a receptor expressed on the surface of T
cells and ACTS as a negative regulator of T cell function. Monoclonal antibody blocking the
activity of PD-1 can successfully reduce tumor load and has been widely used in the clinical
treatment of various tumors.
The immune imbalance in patients with sepsis has many similarities tumors. PD-1 and PD-L1 are
key mediators in T cell depletion in sepsis patients. Animal models have shown that blocking
PD-1 or PD-L1 can prevent T cell death, regulate cytokine production, reduce organ
dysfunction and reduce death in sepsis. Previous study showed the clinical safety of
anti-PD-1 antibody in sepsis patients through randomized, placebo-controlled trials.
Thymosin has also been proved to regulate cellular immunity in sepsis patients. Some studies
have shown that thymosin can significantly reduce the mortality of sepsis patients. At
present, phase III clinical research is in progress to further clarify the role of thymosin
in patients with sepsis. The purpose of this study was to investigate the efficacy of PD-1
and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel
coronavirus infection.
Drug: PD-1 blocking antibody+standard treatment
After randomization, PD-1 blocking antibody 200mg iv, one time. Standard treatment is according to the protocol of treatment of 2019-nCoV infection
Drug: Thymosin+standard treatment
Thymosin 1.6 mg sc qd, last for 5 days. Standard treatment is according to the protocol of treatment of 2019-nCoV infection
Other: standard treatment
Standard treatment is according to the protocol of treatment of 2019-nCoV infection
Inclusion Criteria:
1. Adult SARI patients with 2019-ncov infection confirmed by PCR;
2. Absolute value of lymphocytes < 0. 6x 109/L;
3. Severe respiratory failure within 48 hours and requires admission to ICU. (severe
respiratory failure was defined as PaO2/FiO2 < 200 mmHg and was supported by positive
pressure mechanical ventilation (including non-invasive and invasive mechanical
ventilation, PEEP>=5cmH2O))
Exclusion Criteria:
1. Age < 18
2. Pregnant
3. Allergic to experimental drugs
4. The underlying disease is very serious and the expected survival time is less than 6
months (such as advanced malignant tumor);
5. COPD or end-stage lung disease requires home oxygen therapy
6. Expected survival time not exceeding 48 hours
7. Participated in other clinical intervention trials within the last 3 months
8. Autoimmune diseases
9. A history of organ, bone marrow or hematopoietic stem cell transplantation 10.
Received radiotherapy and chemotherapy for malignant tumor within 6 months
11.HIV infected patients or diagnosed with acquired immunodeficiency within the past year
(CD4 T cells <=200/mm3) 12. Patients receiving anti-hcv treatment 13.90 days of retinal
detachment or eye surgery 14. Permanent blindness in one eye 15. History of iritis,
endophthalmitis, scleral inflammation or retinitis 16. The competent physician considered
it inappropriate to participate in the study