PFC/M1 activation and excitability: a longitudinal cohort study on fatigue symptoms in healthcare workers post-COVID-19 (preprint)

Background Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection.Methods A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course.Results At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients.Conclusions Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation.Trial registration The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1, registered February 3, 2023. The Chinese Clinical Trial Registry, ChiCTR2300068444, registered February 20, 2023. https://www.chictr.org.cn

Patients with Advanced Pancreatic & Biliary Cancer Appear More Vulnerable to SARS-CoV-2 Omicron Variant: An Observational Study during the COVID-19 Outbreak in Shanghai (preprint)

Background:There is a great controversy about lethal effect of Omicron Variant on vulnerable populations and the measure of full-open or zero community transmission policy. Thus, we designed an observational study to evaluate the outcomes of Omicron-infected patients with pancreatic & biliary cancer (the so-called “King of Cancer”) in order to provide potential evidence for the most appropriate strategy to counter Omicron transmission in Shanghai.Methods: Omicron infected patients with advanced pancreatic & biliary cancer were enrolled from April 15 to May 31, 2022. Four groups were set in this study: Group 1, Omicron-infected cancer patients (N=4); Group 2, non-infected cancer patients (N=4); Group 3, infected non-cancer-afflicted subjects (N=4); Group 4, non-infected non-cancer-afflicted subjects (N=4). On Day 0, 7 and 14 after infection, the blood samples were dynamically collected from all subjects. The primary endpoints were disease severity and survival. Results:By the endpoints in this observational study, Patients No. 2, 3 and 4 died separately at Day 11, 25 and 13 after viral infection, all of whom were patients with advanced cancer, with the death rate up to 75%. Group 1 presented an overall T cell exhaustion status compared with other groups with obviously lower T cell populations and higher B cell% and CD4+T/CD8+T ratio (P<0.05). Time-course cytokine monitoring results showed that IL-1β was significantly decreased in Group 1 (P<0.05) and generally kept at a low level without obvious fluctuation. IL-6 was markedly increased in infected cancer patients (P<0.01), but remained a low level and had no apparent change during the whole infection process in non-cancer-afflicted subjects. Furthermore, several inflammatory parameter indexes indicated a tight association of Omicron infection with disease course and prognosis of Omicron-infected cancer patients.Conclusions:For patients with advanced pancreatic & biliary cancer, the strict & comprehensive control strategy for COVID-19 epidemic in Shanghai provided a guarantee of low infection and death rate. Conclusively, this policy shall be persisted upon the consideration of the welfare of vulnerable populations.

Incidence of Mortality, Acute Kidney Injury and Graft Loss in Adult Kidney Transplant Recipients with Coronavirus Disease 2019: Systematic Review and Meta-Analysis.

The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19-23%), an intensive care unit admission rate of 26% (95% CI: 22-31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62-81%), an acute kidney injury rate of 44% (95% CI: 39-49%), a kidney replacement therapy rate of 12% (95% CI: 9-15%), and a graft loss rate of 8% (95% CI: 5-15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.

Immunogenicity Rates After SARS-CoV-2 Vaccination in People With End-stage Kidney Disease: A Systematic Review and Meta-analysis.

Importance: Adults receiving dialysis treatment have a higher likelihood of death when infected with SARS-CoV-2 than adults not receiving dialysis treatment. To date, the immune response of people receiving dialysis after SARS-CoV-2 vaccination has not been systematically discussed. Objective: To assess immunogenicity rates in people with end-stage kidney disease (ESKD) receiving SARS-CoV-2 vaccines, explore postvaccination potential risk factors for nonresponse, and assess whether receiving dialysis is associated with different antibody response rates compared with the nondialysis population. Data Sources: This systematic review and meta-analysis used articles from PubMed, Medline, and Embase published before July 30, 2021, as well as articles in the medRxiv preprint server. Study Selection: Studies that evaluated the immunogenicity rate according to the postvaccine antibody response rate in patients with ESKD receiving dialysis were selected. Data Extraction and Synthesis: The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A random-effects model was used. Two independent reviewers conducted the literature search and extracted the data. Main Outcomes and Measures: The primary outcome was the pooled antibody postvaccine response rates in individuals with ESKD. The secondary outcomes were pooled response rates in individuals receiving and not receiving dialysis. Subgroup analysis and meta-regression were conducted to identify the sources of heterogeneity. Results: A total of 32 studies were included. The overall immunogenicity rate of the dialysis group was 86% (95% CI, 81%-89%). Meta-regression showed a significant difference was detected in the postvaccine response rate on the basis of prevalence of diabetes (regression coefficient, -0.06; 95% CI, -0.10 to -0.02; P = .004). Compared with nondialysis controls, patients in the dialysis group had a lower response rate after the first (relative risk [RR], 0.61; 95% CI, 0.47-0.79; I2 = 70.2%) and second (RR, 0.88; 95% CI, 0.82-0.93; I2 = 72.2%) doses, with statistically significantly increased RR between first and second doses (P = .007). Conclusions and Relevance: These findings suggest that the immunogenicity rate among patients receiving dialysis was 41% after the first dose and 89% after the second dose. Diabetes might be a risk factor for nonresponse in the dialysis population. Patients receiving dialysis had a poorer antibody response rate than did individuals not receiving dialysis, particularly after the first dose.

DNA damage contributes to age-associated differences in SARS-CoV-2 infection (preprint)

Coronavirus disease 2019 (COVID-19), caused by coronavirus SARS-CoV-2, is known to disproportionately affect older individuals1,2. How aging processes affect the disease progression remains largely unknown. Here we found that DNA damage, one of the major causes of aging3, promoted susceptibility to SARS-CoV-2 infection in cells and intestinal organoids. SARS-CoV-2 entry was facilitated by DNA damage caused by telomere attrition or extrinsic genotoxic stress and hampered by inhibition of DNA damage response (DDR). Mechanistic analysis revealed that DDR increased expression of ACE2, the receptor of SARS-CoV-2, by activation of transcription factor c-Jun in vitro and in vivo. Expression of ACE2 was elevated in the older tissues and positively correlated with γH2Ax and phosphorylated c-Jun (p-c-Jun). Finally, targeting DNA damage by increasing the DNA repair capacity, alleviated cell susceptibility to SARS-CoV-2. Our data provide insights into the age-associated differences in SARS-CoV-2 infection and a novel target for anti-viral intervention.

Exploring the Mechanisms of Lian Hua Qing Wen Capsule against COVID-19 by Network Pharmacology and Molecular Docking Approach (preprint)

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) disease has led to a wide-spread global pandemic. There is no specific antiviral drug proven effective for the treatment of patients with COVID-19 at present. Combination of western and traditional Chinese medicine (TCM) is recommended, and Lian Hua Qing Wen (LHQW) capsule is a basic prescription and widely used to treat COVID-19 in China. However, the mechanisms of LHQW capsule treating COVID-19 are not clear. The aim of the study is to explore the mechanisms of LHQW capsule treating COVID-19 based on network pharmacy and molecular docking approach. Methods The active compounds and targets of LHQW capsule were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). COVID-19 related target genes were obtained from GeneCards database and OMIM database. Protein–protein interaction (PPI) networks of LHQW capsule targets and COVID-19-related genes were visualized and merged to identify the candidate targets for LHQW capsule treating COVID-19. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed. The hub genes involved in the gene-related pathways were screened and their corresponding compounds were used for in vitro validation of molecular docking predictions.Results A total of 185 active compounds of LHQW capsule were screened out, and 263 targets were predicted. Third hundred and fifty-two COVID-19 related target genes were obtained from GeneCards database and OMIM database. GO functional enrichment analysis showed that the biological processes of LHQW capsule treating COVID-19 were closely linked with the regulation of inflammation, immunity, cytokines production, vascular permeability, oxidative stress and apoptosis. KEGG enrichment analysis revealed that the pathways of LHQW capsule treating COVID-19 were significantly enriched in AGE−RAGE signaling pathway in diabetic complications, Kaposi sarcoma−associated herpesvirus infection, TNF, IL−17, and Toll−like receptor (TLR) signaling pathway. The hub targets genes in the gene-related pathways analysis of LHQW capsule treating COVID-19 included MAPK1, MAPK3, RELA, IL-6 and CASP8, which closely associated with inflammation, cytokines storm and apoptosis. Finally, molecular docking showed that top 5 compounds of LHQW capsule also had good binding activities to the important targets in COVID-19.Conclusions The mechanisms of LHQW capsule treating COVID-19 may involve in inhibiting inflammatory response, cytokine storm and virus infection, and regulating immune reactions, apoptosis and endothelial barrier.

Construction of Integrated Emergency Management Model for Novel Coronavirus Pneumonia Epidemic Prevention and Control in Hospital Pharmacy Department / 中国药房

OBJECTIVE： To provide reference for improving emergency capacity of the hospital pharmacy department in response to the novel coronavirus pneumonia （COVID-19） epidemic. METHODS ：According to the related regulations and requirements of Law of the People ’s Republic of China on the Prevention and Control of Infectious Diseases ，combined with the situation of COVID- 19 epidemic prevention and control ，and management experience of relevant hospitals ，on the basis of in-depth analysis of drug supply and quality assurance ，drug dispensing management ，provision of clinical pharmaceutical services and other related material support of hospital pharmacy department，integrated emergency management model was constructed for COVID- 19 epidemic prevention and control ，and the precautions and response measures of each link were sorted out. RESULTS ：Integruted emergency management mode for COVID-19 epidemic prevention and control in hospital pharmacy department included but was not limited to human resource management，drug and disinfection products supply management （mainly including key treatment drugs and disinfection product list formulation，control，inventory increase ，etc.）；drug dispensing management （mainly including prescription ，pharmacy window ， planning quantitative reserve ， drug return ， etc.）；clinical pharmaceutical care management （mainly including providing pharmaceutical information support ，online pharmaceutical service ，monitoring drug safety ，etc.）；personnel protection and disinfection （mainly including personnel protection ，environment and window ，equipment and container ，paper prescription disinfection，etc.）；special management of donated drugs ；prevention and control knowledge training ；pharmaceutical education and scientific research management ，etc. CONCLUSIONS ：The integrated emergency management model for epidemic prevention and control is helpful for hospital pharmacy to manage public health emergencies. During the outbreak of COVID- 19，hospital pharmacy department should start integrated emergency management mode for epidemic prevention and control ，strengthen the risk control of each link ，and play a good role in the key functional departments in the special period.

Report of the first cases of mother and infant infections with 2019 novel coronavirus in Xinyang City Henan Province / 中华传染病杂志

Objective@#To report the first case of a neonatal pneumonia with 2019-nCoV infection, and the experience of successfully diagnosis and treatment in late pregnancy woman with novel coronavirus pneumonia (critical type) in Xinyang city.@*Methods@#The successfully diagnosis and treatment of a woman with 38 weeks singleton pregnancy complicated with novel coronavirus pneumonia (critical type), and a case of neonatal pneumonia with 2019-nCoV infection were retrospectively analyzed.@*Results@#A single male was successfully delivered at 38-week gestation of his mother by cesarean section under third level protection in operation room. The delivery woman was diagnosed with 2019-nCoV infection at day 2 of delivery. Dyspnea and severe hypoxemia soon developed, and invasive mechanical ventilation was given. After active rescue and treatment, the delivery woman had been taken off line successfully and the condition was stable. Pharyngeal swab specimen of the neonate was sent for examination 3 days after birth, and was positive for novel coronavirus nucleic acid by fluorescence reverse transcript polymerase chain reaction.@*Conclusion@#2019-nCoV may be transmitted vertically from mother to child.

Clinical analysis of 23 cases of 2019 novel coronavirus infection in Xinyang City, Henan Province / 中华危重病急救医学

Objective@#To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection, so as to provide basis for clinical diagnosis.@*Methods@#The epidemiology, clinical symptoms, laboratory and radiologic data of 23 patients with 2019-nCoV infection admitted to the Fifth People's Hospital of Xinyang City from January 22,2020 to January 29, 2020 were retrospectively analyzed.@*Results@#The 23 patients with 2019 nCov infection consisted of 15 men and 8 women, and the median age was 46.0 (40.5, 52.0) years (27-80 years); 9 of them had basic disease (39%), including hypertension (17%), cardiovascular diseases (17%), diabetes (9%), hypothyroidism (4%) and old tuberculosis (4%). All the 23 patients had contact history in Wuhan area or with confirmed infections. Clinical symptoms included: fever (100%), cough (70%), expectoration (43%), myalgia (26%), headache (17%) and dyspnea (17%), and the less common symptoms were diarrhea (4.3%). Blood routine test: white blood cells (WBC) < 4×109/L in 11 cases (48%), (4-10)×109/L in 10 cases (43%), >10 × 109/L in 2 cases (9%); lymphocytopenia in 13 cases (56%). All 23 patients had different degrees of infective lesions in chest CT examination, with 9 cases (39%) on one side and 14 cases (61%) on both sides. Classification: 19 mild cases, 4 severe cases, no critical or death case. Complications included acute respiratory distress syndrome [4 (17%)]. No case was reported with the damage of liver or kidney function and with secondary infection.@*Conclusions@#Epidemic history of contact, fever, pneumonia signs of chest CT, normal or decreased count of WBC and lymphocytopenia are the clinical basis for diagnosis of the disease. However, at present, the treatment of patients has not been completed, the effective treatment strategy and final prognosis are not clear.