Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy.

Lymphoma, which is highly malignant, stems from lymph nodes and lymphoid tissue. Lymphoma cells express programmed death-ligand 1/2 (PD-L1/PD-L2), which binds with programmed cell death 1 protein (PD-1) to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance. Recently, immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors (nivolumab and pembrolizumab) have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients. Accordingly, the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually, which results in an increasing number of patients developing immune-related adverse events (irAEs). The occurrence of irAEs inevitably affects the benefits provided by immunotherapy, particularly when PD-1 inhibitors are applied. However, the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation. This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors. A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

Retrospective Study of Aging and Sex-Specific Risk Factors of COVID-19 with Hypertension in China.

Background: Coronavirus disease 2019 (COVID-19) has been a global threat that pushes healthcare to its limits. Hypertension is one of the most common risk factors for cardiovascular complications in COVID-19 and is strongly associated with disease severity and mortality. To date, clinical mechanisms by which hypertension leads to increased risk in COVID-19 are still unclear. Furthermore, additional factors might increase these risks, such as the consideration of age and sex, which are of interest when in search of personalized treatments for hypertensive COVID-19 patients. Methods: We conducted a retrospective cohort study of 543 COVID-19 patients in seven provinces of China to examine the epidemiological and clinical characteristics of COVID-19 in this population and to determine risk factors of hypertensive COVID-19 patients. We also used univariable and multivariable logistic regression methods to explore the risk factors associated with hypertensive COVID-19 patients in different age and sex subgroups. Results: Among the enrolled COVID-19 patients, the median age was 47 years (interquartile range (IQR) 34.0-57.0), and 99 patients (18.23%) were over 60 years old. With regard to comorbidities, 91 patients (16.75%) were diagnosed with hypertension, followed by diabetes, coronary disease, and cerebrovascular disease. Of the hypertensive COVID-19 patients, 51 (56.04%) were male. Multivariable analysis showed that old age, comorbid diabetes or coronary heart disease on admission, increased D-dimer, increased glucose, and decreased lymphocyte count were independent risk factors associated with hypertensive COVID-19 patients. Elevated total bilirubin (odds ratio [OR]: 1.014, 95% confidence interval [CI]: 0.23-1.05; p = 0.043) and triglycerides (OR: 1.173, 95% CI: 0.049-1.617; p = 0.007) were found to be associated with elderly hypertensive COVID-19 patients. In addition, we found that decreased lymphocytes, basophil, high-density lipoprotein, and increased fibrinogen and creatinine were related to a higher risk of disease severity in male patients. The most common abnormal clinical findings pertaining to female hypertensive COVID-19 patients were hemoglobin, total bile acid, total protein, and low-density lipoprotein. Conclusions: Factors associated with increased risk of hypertensive COVID-19 patients were identified. Results to the different age and sex subgroups in our study will allow for better possible personalized care and also provide new insights into specific risk stratification, disease management, and treatment strategies for COVID-19 patients with hypertension in the future.

Immune response and homeostasis mechanism following administration of BBIBP-CorV SARS-CoV-2 inactivated vaccine.

The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16+ monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8+ T cells, along with increased activation of CD4+ T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4+ T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination. Additionally, comparative analysis revealed higher neutralizing antibody levels, distinct expansion of naive T cells, a shared increased proportion of regulatory CD4+ T cells, and upregulated expression of functional genes in booster dose recipients with a longer interval after the second vaccination. Our research will support a comprehensive understanding of the systemic immune responses elicited by the BBIBP-CorV inactivated vaccine, which will facilitate the formulation of better vaccination strategies and the design of new vaccines.

Relationship between nosocomial infections and coronavirus disease 2019 in the neurosurgery unit: clinical characteristics and outcomes from a Chinese Tertiary-Care Hospital.

BACKGROUND: The COVID-19 pandemic has raised awareness of infection prevention and control. We found that the incidence of nosocomial infection in neurosurgery has changed. This study aimed to evaluate the impact of "coronavirus disease 2019 (COVID-19) prevention and control measures" on nosocomial infections in neurosurgery. METHODS: To explore changes in nosocomial infections in neurosurgery during the COVID-19 pandemic, the clinical data of inpatients undergoing neurosurgery at Taizhou Hospital of Zhejiang Province between January 1 and April 30, 2020 (COVID-19 era) were first analyzed and then compared with those from same period in 2019 (first pre-COVID-19 era). We also analyzed data between May 1 and December 31, 2020 (post-COVID-19 era) at the same time in 2019 (second pre-COVID-19 era). RESULTS: The nosocomial infection rate was 7.85% (54/688) in the first pre-COVID-19 era and 4.30% (26/605) in the COVID-19 era (P = 0.01). The respiratory system infection rate between the first pre-COVID-19 and COVID-19 eras was 6.1% vs. 2.0% (P < 0.01), while the urinary system infection rate was 1.7% vs. 2.0% (P = 0.84). Between the first pre-COVID-19 and COVID-19 eras, respiratory system and urinary infections accounted for 77.78% (42/54) vs. 46.15% (12/26) and 22.22% (12/54) vs. 46.15% (12/26) of the total nosocomial infections, respectively (P < 0.01). Between the second pre-COVID-19 and post-COVID-19 eras, respiratory system and urinary accounted for 53.66% (44/82) vs. 40.63% (39/96) and 24.39% (20/82) vs. 40.63% (39/96) of the total nosocomial infections, respectively (P = 0.02). CONCLUSIONS: The incidence of nosocomial infections in neurosurgery reduced during the COVID-19 pandemic. The reduction was primarily observed in respiratory infections, while the proportion of urinary infections increased significantly.

A map of bat virus receptors derived from single-cell multiomics.

Bats are considered reservoirs of many lethal zoonotic viruses and have been implicated in several outbreaks of emerging infectious diseases, such as SARS-CoV, MERS-CoV, and SARS-CoV-2. It is necessary to systematically derive the expression patterns of bat virus receptors and their regulatory features for future research into bat-borne viruses and the prediction and prevention of pandemics. Here, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) of major organ samples collected from Chinese horseshoe bats (Rhinolophus affinis) and systematically checked the expression pattern of bat-related virus receptors and chromatin accessibility across organs and cell types, providing a valuable dataset for studying the nature of infection among bat-borne viruses.

Trends in secondary inorganic aerosol pollution in China and its responses to emission controls of precursors in wintertime

The Chinese government recently proposed ammonia (NH3) emission reductions (but without a specific national target) as a strategic option to mitigate fine particulate matter (PM2.5) pollution. We combined a meta-analysis of nationwide measurements and air quality modeling to identify efficiency gains by striking a balance between controlling NH3 and acid gas (SO2 and NOx) emissions. We found that PM2.5 concentrations decreased from 2000 to 2019, but annual mean PM2.5 concentrations still exceeded 35 µg m-3 at 74 % of 1498 monitoring sites during 2015–2019. The concentration of PM2.5 and its components were significantly higher (16 %–195 %) on hazy days than on non-hazy days. Compared with mean values of other components, this difference was more significant for the secondary inorganic ions SO42-, NO3-, and NH4+ (average increase 98 %). While sulfate concentrations significantly decreased over this period, no significant change was observed for nitrate and ammonium concentrations. Model simulations indicate that the effectiveness of a 50 % NH3 emission reduction for controlling secondary inorganic aerosol (SIA) concentrations decreased from 2010 to 2017 in four megacity clusters of eastern China, simulated for the month of January under fixed meteorological conditions (2010). Although the effectiveness further declined in 2020 for simulations including the natural experiment of substantial reductions in acid gas emissions during the COVID-19 pandemic, the resulting reductions in SIA concentrations were on average 20.8 % lower than those in 2017. In addition, the reduction in SIA concentrations in 2017 was greater for 50 % acid gas reductions than for the 50 % NH3 emission reductions. Our findings indicate that persistent secondary inorganic aerosol pollution in China is limited by emissions of acid gases, while an additional control of NH3 emissions would become more important as reductions of SO2 and NOx emissions progress.

Flexible, anti-damage, and non-contact sensing electronic skin implanted with MWCNT to block public pathogens contact infection.

If a person comes into contact with pathogens on public facilities, there is a threat of contact (skin/wound) infections. More urgently, there are also reports about COVID-19 coronavirus contact infection, which once again reminds that contact infection is a very easily overlooked disease exposure route. Herein, we propose an innovative implantation strategy to fabricate a multi-walled carbon nanotube/polyvinyl alcohol (MWCNT/PVA, MCP) interpenetrating interface to achieve flexibility, anti-damage, and non-contact sensing electronic skin (E-skin). Interestingly, the MCP E-skin had a fascinating non-contact sensing function, which can respond to the finger approaching 0-20 mm through the spatial weak field. This non-contact sensing can be applied urgently to human-machine interactions in public facilities to block pathogen. The scratches of the fruit knife did not damage the MCP E-skin, and can resist chemical corrosion after hydrophobic treatment. In addition, the MCP E-skin was developed to real-time monitor the respiratory and cough for exercise detection and disease diagnosis. Notably, the MCP E-skin has great potential for emergency applications in times of infectious disease pandemics. Electronic Supplementary Material: Supplementary material (fabrication of MCP E-skin, laser confocal tomography, parameter optimization, mechanical property characterization, finite element simulation, sensing mechanism, signal processing) is available in the online version of this article at 10.1007/s12274-021-3831-z.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.

OBJECTIVE: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. METHODS: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. RESULTS: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. CONCLUSION: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Risk Factors in Patients with Diabetes Hospitalized for COVID-19: Findings from a Multicenter Retrospective Study.

METHODS: In this multicenter retrospective study, patients with COVID-19 in China were included and classified into two groups according to whether they were complicated with diabetes or not. Demographic symptoms and laboratory data were extracted from medical records. Univariable and multivariable logistic regression methods were used to explore the risk factors. RESULTS: 538 COVID-19 patients were finally included in this study, of whom 492 were nondiabetes and 46 were diabetes. The median age was 47 years (IQR 35.0-56.0). And the elderly patients with diabetes were more likely to have dry cough, and the alanine aminotransferase, lactate dehydrogenase, Ca, and mean hemoglobin recovery rate were higher than the other groups. Furthermore, we also found the liver and kidney function of male patients was worse than that of female patients, while female cases should be paid more attention to the occurrence of bleeding and electrolyte disorders. Moreover, advance age, blood glucose, gender, prothrombin time, and total cholesterol could be considered as risk factors for COVID-19 patients with diabetes through the multivariable logistic regression model in our study. CONCLUSION: The potential risk factors found in our study showed a major piece of the complex puzzle linking diabetes and COVID-19 infection. Meanwhile, focusing on gender and age factors in COVID-19 patients with or without diabetes, specific clinical characteristics, and risk factors should be paid more attention by clinicians to figure out a targeted intervention to improve clinical efficacy worldwide.

Clinical features and risk factors for severe inpatients with COVID-19: A retrospective study in China.

BACKGROUND: A worldwide outbreak of coronavirus disease (COVID-19), since 2019, has brought a disaster to people all over the world. Many researchers carried out clinical epidemiological studies on patients with COVID-19 previously, but risk factors for patients with different levels of severity are still unclear. METHODS: 562 patients with laboratory-confirmed COVID-19 from 12 hospitals in China were included in this retrospective study. Related clinical information, therapies, and imaging data were extracted from electronic medical records and compared between patients with severe and non-severe status. We explored the risk factors associated with different severity of COVID-19 patients by logistic regression methods. RESULTS: Based on the guideline we cited, 509 patients were classified as non-severe and 53 were severe. The age range of whom was 5-87 years, with a median age of 47 (IQR 35.0-57.0). And the elderly patients (older than 60 years old) in non-severe group were more likely to suffer from fever and asthma, accompanied by higher level of D-dimer, red blood cell distribution width and low-density lipoprotein. Furthermore, we found that the liver and kidney function of male patients was worse than that of female patients in both severe and non-severe groups with different age levels, while the severe females had faster ESR and lower inflammatory markers. Of major laboratory markers in non-severe cases, baseline albumin and the lymphocyte percentage were higher, while the white blood cell and the neutrophil count were lower. In addition, severe patients were more likely to be accompanied by an increase in cystatin C, mean hemoglobin level and a decrease in oxygen saturation. Besides that, advanced age and indicators such as count of white blood cell, glucose were proved to be the most common risk factors preventing COVID-19 patients from aggravating. CONCLUSION: The potential risk factors found in our study have shown great significance to prevent COVID-19 patients from aggravating and turning to critical cases during treatment. Meanwhile, focusing on gender and age factors in groups with different severity of COVID-19, and paying more attention to specific clinical symptoms and characteristics, could improve efficacy of personalized intervention to treat COVID-19 effectively.