Development and external validation of a prognostic tool for nonsevere COVID-19 inpatients.

To develop a machine learning model and nomogram to predict the probability of persistent virus shedding (PVS) in hospitalized patients with coronavirus disease 2019 (COVID-19), the clinical symptoms and signs, laboratory parameters, cytokines, and immune cell data of 429 patients with nonsevere COVID-19 were retrospectively reviewed. Two models were developed using the Akaike information criterion (AIC). The performance of these two models was analyzed and compared by the receiver operating characteristic (ROC) curve, calibration curve, net reclassification index (NRI), and integrated discrimination improvement (IDI). The final model included the following independent predictors of PVS: sex, C-reactive protein (CRP) level, interleukin-6 (IL-6) level, the neutrophil-lymphocyte ratio (NLR), monocyte count (MC), albumin (ALB) level, and serum potassium level. The model performed well in both the internal validation (corrected C-statistic = 0.748, corrected Brier score = 0.201) and external validation datasets (corrected C-statistic = 0.793, corrected Brier score = 0.190). The internal calibration was very good (corrected slope = 0.910). The model developed in this study showed high discriminant performance in predicting PVS in nonsevere COVID-19 patients. Because of the availability and accessibility of the model, the nomogram designed in this study could provide a useful prognostic tool for clinicians and medical decision-makers.

Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function.

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin (CAP), the main component of chili pepper. Despite studies in several neurological diseases, the role of TRPV1 in demyelinating diseases remains unknown. Herein, we reported that TRPV1 expression was increased within the corpus callosum during demyelination in a cuprizone (CPZ)-induced demyelination mouse model. TRPV1 deficiency exacerbated motor coordinative dysfunction and demyelination in CPZ-treated mice, whereas the TRPV1 agonist CAP improved the behavioral performance and facilitated remyelination. TRPV1 was predominantly expressed in Iba1+ microglia/macrophages in human brain sections of multiple sclerosis patients and mouse corpus callosum under demyelinating conditions. TRPV1 deficiency decreased microglial recruitment to the corpus callosum, with an associated increase in the accumulation of myelin debris. Conversely, the activation of TRPV1 by CAP enhanced the recruitment of microglia to the corpus callosum and potentiated myelin debris clearance. Using real-time live imaging we confirmed an increased phagocytic function of microglia following CAP treatment. In addition, the expression of the scavenger receptor CD36 was increased, and that of the glycolysis regulators Hif1a and Hk2 was decreased. We conclude that TRPV1 is an important regulator of microglial function in the context of demyelination and may serve as a promising therapeutic target for demyelinating diseases such as multiple sclerosis.

Ad5-nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants.

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

H3K9 acetylation modification and TLR9 immune regulation mechanism in patients after anti-HBV treatment.

To improve the curative effect of anti-hepatitis B virus (HBV) drugs, methods such as thymosin and entecavir combination have become a focus of clinical investigation. The aim of this retrospective experimental study was to explore the potential mechanism of action of thymosin a1 (Ta1) combined with entecavir in the treatment of HBV infection. A total of 28 patients with chronic hepatitis B, 29 patients treated with thymosin a1 and entecavir combination, and 15 healthy individuals were enrolled in this study. RT-qPCR was conducted to evaluate the mRNA levels of TLR9 in peripheral blood mononuclear cells (PBMCs). The serum level of TLR9 protein was analyzed by ELISA. The binding of TLR9 gene to the protein H3K9Ac in PBMCs was assessed by chromatin immunoprecipitation, and serum inflammatory factors were detected by Luminex technology. The expression levels of TLR9 mRNA and serum TLR9 protein in patients with HBV infection were significantly lower than those in subjects in the control group before treatment but increased after treatment with the Ta1 and entecavir combination. Moreover, the acetylation protein H3K9Ac was significantly bound to the promoter region of the TLR9 gene in patients with HBV infection treated with the Ta1 and entecavir combination compared to that in patients with HBV infection without treatment. Furthermore, the expression levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interferon gamma, and necrosis factor alpha in patients with HBV infection after the combination treatment were slightly decreased compared to those in patients with HBV infection without treatment. In conclusion, the histone acetylation modification of TLR9 was significantly improved in patients with HBV infection after treatment with the Ta1 and entecavir combination, which elevated the expression of TLR9 at the mRNA and protein levels and further regulated the expression of IL-6, IL-12, and other cytokines.

Prevalence of Dual-Positivity for Both Hepatitis B e Antigen and Hepatitis B e Antibody Among Hospitalized Patients with Chronic Hepatitis B Virus Infection.

OBJECTIVE: The detection of dual-positivity for both hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) is not typically performed for patients with hepatitis B virus (HBV). This cross-sectional study was designed to figure out the prevalence of dual-positivity for both HBeAg and anti-HBe (DEP) among hospitalized patients with chronic hepatitis B virus infection (C-HBVI). PATIENTS AND METHODS: Data from 2820 cases with C-HBVI from two centers in China were retrospectively analyzed. Univariate and multivariate logistic regression analyses were undertaken to identify the risk factors for liver fibrosis (LF) and acute-on-chronic liver failure (ACLF). RESULTS: There were 165 (5.9%), 688, and 1903 patients in DEP, HBeAg+/anti-HBe-, and HBeAg-/anti-HBe+ groups, respectively. The DEP patients' median age was 43.6 years old and 71.5% of them were male. They had higher levels of alanine transaminase, total bilirubin, and international normalized ratio. Furthermore, DEP cases had a higher proportion of liver cirrhosis, and it was associated with non-invasive testing of LF, including aspartate transaminase (AST)-to-platelet ratio index (APRI) >1.5 (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.27-3.03, P = 0.002) and fibrosis-4 (FIB-4) score >1.45 (OR = 2.07, 95% CI: 1.28-3.34, P = 0.003). DEP also contributed to the elevated risk of ACLF (OR = 4.80, 95% CI: 2.02-11.39, P < 0.001). CONCLUSION: DEP cases are at higher risks of LF and ACLF than other patients with HBV infection. A fast diagnosis and an active monitoring of liver diseases for DEP patients are extremely vital.

Comparison of Clinical Features and CT Temporal Changes Between Familial Clusters and Non-familial Patients With COVID-19 Pneumonia.

Purpose: This study aimed to compare the clinical characteristics, laboratory findings, and chest computed tomography (CT) findings of familial cluster (FC) and non-familial (NF) patients with coronavirus disease 2019 (COVID-19) pneumonia. Methods: This retrospective study included 178 symptomatic adult patients with laboratory-confirmed COVID-19. The 178 patients were divided into FC (n = 108) and NF (n = 70) groups. Patients with at least two confirmed COVID-19 cases in their household were classified into the FC group. The clinical and laboratory features between the two groups were compared and so were the chest CT findings on-admission and end-hospitalization. Results: Compared with the NF group, the FC group had a longer period of exposure (13.1 vs. 8.9 days, p < 0.001), viral shedding (21.5 vs. 15.9 days, p < 0.001), and hospital stay (39.2 vs. 22.2 days, p < 0.001). The FC group showed a higher number of involved lung lobes on admission (3.0 vs. 2.3, p = 0.017) and at end-hospitalization (3.6 vs. 1.7, p < 0.001) as well as higher sum severity CT scores at end-hospitalization (4.6 vs. 2.7, p = 0.005) than did the NF group. Conversely, the FC group had a lower lymphocyte count level (p < 0.001) and a significantly lower difference in the number of involved lung lobes (Δnumber) between admission and discharge (p < 0.001). Notably, more cases of severe or critical illness were observed in the FC group than in the NF group (p = 0.036). Conclusions: Patients in the FC group had a worse clinical course and outcome than those in the NF group; thus, close monitoring during treatment and follow-ups after discharge would be beneficial for patients with familial infections.

Mean platelet volume/platelet count ratio predicts severe pneumonia of COVID-19.

BACKGROUND: Although platelet mean volume/platelet count ratio (MPR) is considered to be a crucial marker of inflammatory and infectious diseases, the relationship between MPR and novel coronavirus infectious disease 2019 (COVID-19) remains unclear. METHODS: In this retrospective study, 85 patients with confirmed COVID-19 were enrolled and divided into low and high MPR group. Data from repeated measures were compared by the generalized estimating equations. Cox regression analyses were performed to assess the impact of MPR on the incidence of severe pneumonia (SP), with inverse probability of treatment weighting (IPTW) used to reduce confounding bias. The primary outcome is the incidence of SP of COVID-19. RESULTS: During follow-up, 17 (20.0%) patients were developed to SP. Compared with mild patients, patients with SP developed showed a higher MPR level at baseline, day 1, day 2, and day 3 after admission (P = .005, P = .015, P = .009, and P = .032, respectively). Kaplan-Meier method showed a higher incidence of SP in the high MPR group than the low MPR group (log-rank test = 10.66, P = .001). After adjustment, high MPR was associated with an elevated incidence of SP (HR, 5.841, 95% CI, 1.566-21.791, P = .009). The IPTW method also suggested that MPR was a significant factor related to the incidence of SP (HR, 8.337, 95% CI, 4.045-17.182, P < .001). CONCLUSION: High MPR level is an independent risk factor for severe pneumonia in patients with COVID-19.

Positive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19).

OBJECTIVES: To investigate the widely concerned issue about positive real-time reverse transcription polymerase chain reaction (RT-PCR) test results after discharge in patients recovered from coronavirus disease 2019 (COVID-19). METHODS: We identified seven cases of COVID-19 who was readmitted to hospital because of positive RT-PCR after discharge, including three pediatrics and four young adult patients. RESULTS: Six patients had positive rectal swabs but negative throat swabs, and one patient had positive throat swabs. All the patients continued to be asymptomatic and had unchanged chest computed tomography from previous images. The time from hospital discharge to positive RT-PCR after recovery was 7-11 days. The time from positive to negative rectal swabs was 5-23 days. CONCLUSION: The study might suggest the positive RT-PCR after recovery did not mean disease relapse or virus reinfection. Adding RT-PCR test of rectal swabs to the criteria for discharge or discontinuation of quarantine might be necessary.

Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

As of March 24, 2020, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for 379,661 infection cases with 16,428 deaths globally, and the number is still increasing rapidly. Herein, we present four critically ill patients with SARS-CoV-2 infection who received supportive care and convalescent plasma. Although all four patients (including a pregnant woman) recovered from SARS-CoV-2 infection eventually, randomized trials are needed to eliminate the effect of other treatments and investigate the safety and efficacy of convalescent plasma therapy.

Removal of cyanide from dilute solution using a cell with three-phase three-dimensional electrode.

The removal of cyanide from dilute solutions containing free cyanide or cuprocyanide was experimentally investigated using a new electrochemical reactor, three-phase three-dimensional electrode cell. The experimental results were assessed in term of removal efficiency of cyanide. The results showed that the reactor could efficiently remove cyanide from the two solutions. The removal efficiency reached as high as about 93% for the two solutions by electrolysis for 10 min at 20 V cell voltage and 0.16 m3/h airflow. It was also observed that the removal efficiency depended on the applied cell voltage, airflow, interelectrode and initial pH value of the containing-cyanide solution. The former two factors have a positive effect while the latter two have a negative effect on cyanide removal in the experimental range.