BackgroundThe response to glucocorticoids treatment may be different between Covid-19 and SARS. MethodsIn this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, ClinicalTrials.gov, ICTRP from 2002 to October 7, 2020. We used fixed-effects and random-effects models to compute the risk ratio of death in the group receiving glucocorticoids treatment and the control group for COVID-19 and SARS, respectively.ResultsTen trials and 71 observational studies, with a total of 45935 patients, were identified. Glucocorticoids treatment, was associated with decreased all-cause mortality both in COVID-19 (risk ratio, 0.88; 95% confidence interval, 0.82 to 0.94; I2=26%) and SARS (0.48; 0.29 to 0.79; 10%), based on high quality evidence, as well as decreased all-cause mortality-including composite outcome of COVID-19 (0.89; 0.82 to 0.98; 0%). In subgroup analyses, all-cause mortality was significantly lower among COVID-19 patients being accompanied by severe ARDS but not mild ARDS, taking low-dose or pulse glucocorticoids, being critically severe but not only severe, being of critical severity and old but not young, being of critical severity and men but not women, non-early taking glucocorticoids and taking dexamethasone or methylprednisolone; but for SARS, lower mortality were observed among those who were taking medium-high dose glucocorticoids, being severe or critically severe, early taking glucocorticoids, and taking dexamethasone or prednisolone. ConclusionsGlucocorticoids treatment reduced mortality in COVID-19 and SARS patients of critical severity; however, different curative effects existed between the two diseases among subpopulations, mainly regarding sex- and age-specific effects, optimal doses and use timing of glucocorticoids.

We investigate whether interleukin-10 (IL-10)-1082 G/G genotype is associated with the mortality rate of acute respiratory distress syndrome (ARDS) in a hospital-based case-control study in China conducted on 314 patients with ARDS and 210 controls admitted to an intensive care unit for sepsis, trauma, aspiration, or massive transfusions. IL-10-1082 promoter polymorphisms were analyzed with polymerase chain reaction amplification followed by restriction fragment length polymorphism. Mortality was recorded if it occurred within 30 days from admission. The -1082G/G genotype was associated with lower frequency of ARDS (odds ratios=0.51; 95% confidence intervals: 0.34-0.76; p=0.001), and in patients with ARDS, it was associated with lower mortality within 30 days (odds ratios=0.44; 95% confidence intervals: 0.25-0.76; p=0.003) than in controls. We conclude that IL-10-1082 G/G genotype is associated with a decreased rate development of ARDS and mortality in this Chinese population.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. However, how this dysregulation occurs remains unclear. Herein, we used scRNA-seq to define the immune landscape of infection and found that when sepsis occurred, adaptive immunity was acutely and strongly suppressed, which manifested as a striking increase in the number of myeloid-derived suppressor cells (MDSCs), a decrease in the number of lymphocytes and drastic downregulation of the expression levels of B-cell-related genes and MHC class II molecules. Transcriptomic analysis showed that systemic immunosuppression occurred not only in the peripheral blood but also in all other immune compartments, including the spleen, lymph nodes, and bone marrow. Patients diagnosed with infection in the emergency department with extremely low expression levels of adaptive immunity-related genes had a high risk for developing sepsis. CD47 was identified as the key molecule that triggered this immunosuppression by inducing the production of amyloid-β precursor protein (App), which caused adaptive immunosuppression via B-cell suppression. Our study outlines a framework for how the dysregulated host response occurs and provides translational opportunities for sepsis immunotherapies.

Background:There are limited data on etiology of viral pneumonia under the impact of COVID-19 pandemic. We aimed to investigate the changes of viral pneumonia before and after COVID-19 pandemic among patients diagnosed with pneumonia. Methods:This is a single-center retrospective study. Patients hospitalized with pneumonia during January 1,2016 and Dec 31,2021 in West China Hospital were included and divided into pre- and post-COVID-19 groups according to the point of COVID-19 outbreak in China which was December 8,2019. Results of the 13 viral nucleic acid tests were compared between the two groups. Results:5,928 patients were analyzed,3,945 in the pre-COVID-19 group while 1,983 in the post-COVID-19. Respiratory viral nucleic acid screening proportion was riseing after COVID-19 (14.8％ VS 22.8％).But the positive rate of post-COVID-19 total virus and Influenza virus had decreased 23.3% and 18.3%, respectively,p＜0.05. The top three viral pneumonia were InfAH1N1(2009),Human Rhinovirus,Human Adenovirus before COVID-19, while HRV, Human Parainfluenza virus, Human Respiratory Syncytial virus after COVID-19 pandemic. Notebly,InfAH1N1(2009) pneumonia decreased to 0％ after the pandemic. Conclusions:Proportion of viral pneumonia has significantly decreased under the impact of COVID-19 pneumonia and the incidence of InfAH1N1(2009) pneumonia is almost 0.

Background: During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. In general, continuous negative viral tests are thought to indicate that the virus has been cleared from the body and that the patients can be considered "recovered". However, because these patients were still critically ill, they obviously had not truly recovered from the disease. We sought to investigate why these patients were still critically ill even though they exhibited negative viral tests by analyzing the gene expression profiles of their peripheral immune cells using transcriptome sequencing.Methods: Fourteen severe COVID-19 patients with at least 3 negative virus tests but were still in critical ill and could not be discharged from the ICU were enrolled. Blood samples from 14 patients and 5 healthy donors were collected. Total RNA was extracted from nucleated cells for RNA-Sequencing. FeatureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. Results: All enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. This adaptive immune suppression is unlikely due to classic immune checkpoint molecules such as PD-1 or long-term use of glucocorticoids but may be caused by an unknown mechanism that has not yet been discovered.Conclusions: Our findings strongly suggest that an initial recovery of these severe COVID-19 patients, as indicated by negative viral tests, may not indicate actual recovery. They still suffer from secondary infections for a long period of time because of severe adaptive immunosuppression and need to receive a variety of antibiotics, antifungal drugs, or combination therapies. Appropriate methods should be used to detect their adaptive immune function, and appropriate immunotherapy that can activate the adaptive immune response should be developed. Trial registration: Not applicable (this study does not involve intervention on human participants).