Nirmatrelvir and ritonavir for inpatients with severe or critical COVID-19 beyond five days of symptom onset: a propensity score-matched, multicenter, retrospective cohort study.

BACKGROUND: There is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient. METHODS: A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated. RESULTS: In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited. CONCLUSIONS: Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.

Impairment of antigen-presenting function of peripheral γδ T cells in patients with sepsis.

Impairment of antigen-presenting functions is a key mechanism contributing to sepsis-induced immunosuppression. Recently, γδ T cells have been demonstrated as professional antigen-presenting cells (APCs); however, their role in sepsis remains unknown. In this in vitro study, the APC function of human peripheral γδ T cells was assessed using samples collected from 42 patients with sepsis and 27 age-matched healthy controls. The APC-related markers HLA-DR, CD27, CD80, and CCR7 on fresh γδT cells were significantly higher in patients with sepsis compared with matched controls; however, they responded poorly to 4-hydroxy-3-methyl-2-butenyl pyrophosphate (HMBPP) stimulation, characterized by the deactivation of these APC markers and impaired proliferation. Furthermore, the adhesion function of γδ T cells, essential for antigen presentation, was greatly reduced in patients with sepsis; for instance, in co-cultures with green fluorescent protein-expressing Escherichia coli, HMBPP-activated γδT cells from healthy individuals adhered to E. coli efficiently, whereas no such phenomenon was observed with respect to γδT cells from patients with sepsis. In line with these results, in co-cultures with isolated CD4+ αß T cells, HMBPP-activated γδT cells of healthy individuals promoted the efficient proliferation of CD4+ αß T cells, whereas γδT cells from patients with sepsis did not do so. In conclusion, our findings show that the antigen-presenting function of γδT cells is severely impaired in patients with sepsis and the mechanisms behind need further study.

Comparative study on the incidence of non-COVID-19 viral pneumonia before and after the COVID-19 pandemic: A retrospective analysis based on respiratory non-COVID viral nucleic acid results.

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on the etiology of non-COVID-19 viral pneumonia remains to be identified. We investigated the evolution of non-COVID-19 viral pneumonia in hospitalized patients before and after the COVID-19 pandemic. Methods: This is a single-center retrospective study. Patients who came to West China Hospital of Sichuan University diagnosed with non-COVID-19 viral pneumonia from January 1, 2016 to December 31, 2021, were included and divided into pre- and post-COVID-19 groups according to the date of the COVID-19 outbreak in China. The results of 13 viral nucleic acid tests were compared between the two groups. Results: A total of 5937 patients (3954 in the pre-COVID-19 group and 1983 in the post-COVID-19 group) were analyzed. Compared with the pre-COVID-19 group, the proportion of patients tested for respiratory non-COVID-19 viral nucleic acid was significantly increased in the post-COVID-19 group (14.78% vs. 22.79%, P <0.05). However, the non-COVID-19 virus-positive rates decreased from 37.9% to 14.6% after the COVID-19 outbreak (P < 0.001). Notably, non-COVID-19 viral pneumonia caused by the influenza A virus H1N1 (InfAH1N1) (2009) dropped to 0% after the pandemic. The top three viruses were InfAH1N1 (2009) (13.9%), human rhinovirus (7.4%), and human adenovirus (3.4%) in the pre-COVID-19 group, and human rhinovirus (3.8%), human respiratory syncytial virus (2.0%), human parainfluenza virus (1.1%) and InfAH3N2 (1.1%) in the post-COVID-19 group. Conclusions: The proportion of non-COVID-19 viral pneumonia decreased significantly after the COVID-19 outbreak, among which InfAH1N1 (2009) pneumonia decreased the most dramatically.

Bibliometric study of sepsis-associated liver injury from 2000 to 2023.

BACKGROUND: Sepsis-associated liver injury (SLI) is a severe and prevalent complication of sepsis. AIM: To explore the literature on SLI via a bibliometric approach. METHODS: Reviews and articles correlated with SLI published from January 1, 2000 to October 28, 2023 were searched from the Web of Science Core Collection. Then, the searched data were analyzed using VOSviewer, CiteSpace, and R language. RESULTS: There were 787 publications involved in this paper, comprising 745 articles and 42 reviews. China, the United States, and Germany are the primary publication sources in this area. Studies related to SLI primarily focused on mechanisms of pathogenesis, as evidenced by analyzing keywords, references, and the counting of original research. These studies mainly involved tumor necrosis factor alpha, inflammation, oxidative stress, and nuclear factor-kappa B. CONCLUSION: There is significant growth in the research on SLI. Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms. According to the analyzed literature, the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.

Effect of single-patient room design on the incidence of nosocomial infection in the intensive care unit: a systematic review and meta-analysis.

Background: Previous studies have yielded varying conclusions regarding the impact of single-patient room design on nosocomial infection in the intensive care unit (ICU). We aimed to examine the impact of ICU single-patient room design on infection control. Methods: We conducted a comprehensive search of PubMed, Embase, the Cochrane Library, Web of Science, CNKI, WanFang Data, and CBM databases from inception to October 2023, without language restrictions. We included observational cohort and quasi-experimental studies assessing the effect of single- versus multi-patient rooms on infection control in the ICU. Outcomes measured included the nosocomial infection rate, incidence density of nosocomial infection, nosocomial colonization and infection rate, acquisition rate of multidrug-resistant organisms (MDROs), and nosocomial bacteremia rate. The choice of effect model was determined by heterogeneity. Results: Our final analysis incorporated 12 studies involving 12,719 patients. Compared with multi-patient rooms in the ICU, single-patient rooms demonstrated a significant benefit in reducing the nosocomial infection rate (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.59, 0.79; p < 0.00001). Analysis based on nosocomial infection incidence density revealed a statistically significant reduction in single-patient rooms (OR: 0.64; 95% CI: 0.44, 0.92; p = 0.02). Single-patient rooms were associated with a marked decrease in nosocomial colonization and infection rate (OR: 0.44; 95% CI: 0.32, 0.62; p < 0.00001). Furthermore, patients in single-patient rooms experienced lower nosocomial bacteremia rate (OR: 0.73; 95% CI: 0.59, 0.89; p = 0.002) and lower acquisition rate of MDROs (OR: 0.41; 95% CI: 0.23, 0.73; p = 0.002) than those in multi-patient rooms. Conclusion: Implementation of single-patient rooms represents an effective strategy for reducing nosocomial infections in the ICU. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/).

Targeted Antibiotics for Lower Respiratory Tract Infection with Corynebacterium striatum.

Purpose: To assess the impact of targeted antibiotic therapy on clinical outcomes of patients with lower respiratory tract (LRT) infection with Corynebacterium striatum (C. striatum). Methods: A new propensity score-inverse probability of treatment weighting (IPTW) cohort study was conducted by using 10-year data. The study included LRT infection patients with respiratory secretions cultured positive for C. striatum simultaneously. The primary outcome was all-cause hospital mortality; the secondary outcomes included hospital stay, ICU stay and ventilation time. The safety outcomes were drug-related serum creatinine (Cr) increase and thrombocytopenia. Results: A total of 339 patients were included in the cohort, and 84 (24.78%) initiated vancomycin or linezolid therapy. In the new IPTW cohort, targeted antibiotic therapy did not improve all-cause hospital mortality (P=0.632), and the OR (95% CI) was 0.879 (0.519-1.488). Moreover, targeted antibiotic therapy was not associated with hospital stay (P=0.415), ICU stay (P=0.945) or ventilation time (P=0.885). The side effects of drug-related higher serum Cr (P=0.044) and thrombocytopenic levels (P=0.038) cannot be ignored. Conclusion: Clinical benefits by vancomycin or linezolid targeted against LRT infection with C. striatum were limited and with drug-related side effects. A prospectively designed study is needed to further confirm the results.