Clinical characteristics of pediatric cases infected with the SARS-CoV-2 Omicron variant in a tertiary children's medical center in Shanghai, China.

BACKGROUND: The number of pediatric cases of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has increased. Here, we describe the clinical characteristics of children in a tertiary children's medical center in Shanghai. METHODS: A total of 676 pediatric coronavirus disease 2019 (COVID-19) cases caused by the Omicron variant who were admitted to the Shanghai Children's Medical Center from March 28 to April 30, 2022 were enrolled in this single-center, prospective, observational real-world study. Patient demographics and clinical characteristics, especially COVID-19 vaccine status, were assessed. RESULTS: Children of all ages appeared susceptible to the SARS-CoV-2 Omicron variant, with no significant difference between sexes. A high SARS-CoV-2 viral load upon admission was associated with leukocytopenia, neutropenia, and thrombocytopenia (P = 0.003, P = 0.021, and P = 0.017, respectively) but not with physical symptoms or radiographic chest abnormalities. Univariable linear regression models indicated that comorbidities (P = 0.001) were associated with a longer time until viral clearance, and increasing age (P < 0.001) and two doses of COVID-19 vaccine (P = 0.001) were associated with a shorter time to viral clearance. Multivariable analysis revealed an independent effect of comorbidities (P < 0.001) and age (P = 0.003). The interaction effect between age and comorbidity showed that the negative association between age and time to virus clearance remained significant only in patients without underlying diseases (P < 0.001). CONCLUSION: This study describes the clinical characteristics of children infected with the Omicron variant of SARS-CoV-2 and calls for additional studies to evaluate the effectiveness and safety of vaccination against COVID-19 in children.

The Interaction between Flavonoids and Intestinal Microbes: A Review.

In recent years, research on the interaction between flavonoids and intestinal microbes have prompted a rash of food science, nutriology and biomedicine, complying with future research trends. The gut microbiota plays an essential role in the maintenance of intestinal homeostasis and human health, but once the intestinal flora dysregulation occurs, it may contribute to various diseases. Flavonoids have shown a variety of physiological activities, and are metabolized or biotransformed by gut microbiota, thereby producing new metabolites that promote human health by modulating the composition and structure of intestinal flora. Herein, this review demonstrates the key notion of flavonoids as well as intestinal microbiota and dysbiosis, aiming to provide a comprehensive understanding about how flavonoids regulate the diseases by gut microbiota. Emphasis is placed on the microbiota-flavonoid bidirectional interaction that affects the metabolic fate of flavonoids and their metabolites, thereby influencing their metabolic mechanism, biotransformation, bioavailability and bioactivity. Potentially by focusing on the abundance and diversity of gut microbiota as well as their metabolites such as bile acids, we discuss the influence mechanism of flavonoids on intestinal microbiota by protecting the intestinal barrier function and immune system. Additionally, the microbiota-flavonoid bidirectional interaction plays a crucial role in regulating various diseases. We explain the underlying regulation mechanism of several typical diseases including gastrointestinal diseases, obesity, diabetes and cancer, aiming to provide a theoretical basis and guideline for the promotion of gastrointestinal health as well as the treatment of diseases.

Ultrasound features of abdominal thrombosis in COVID 19 patients.

PURPOSE: Abdominal thromboses are a poorly characterized thrombotic complication of COVID-19. The aim of this paper is to report multimodality ultrasound imaging findings of the abdomen in evaluation of thrombotic lesions in hospitalized patients with COVID-19. PATIENTS & METHODS: In this retrospective observational study, patients admitted to a single University Hospital from April 1 2020 to April 30, 2022, who tested positive for COVID-19 and developed acute abdominal pain over the course of hospitalization were included. Abdominal ultrasound imaging studies performed in these patients were reviewed, including B mode ultrasound (BMUS), color-coded Doppler ultrasound (CCDS) and contrast enhanced ultrasound (CEUS). Thromboembolic findings on CT were also recorded. RESULTS: Finally, 13 cases of abdominal thrombosis in 226 Patients with COVID 19 infections were included (mean age, 56.69±8.97 years; 10 men, 3 women). Thromboembolic events including: iliac thrombosis (n = 4), portal venous (PV) thrombosis (n = 3), superior mesenteric vein (VMS) thrombosis (n = 2), inferior vena cava (IVC) thrombosis (n = 5) and inferior mesenteric vein (VMI) thrombosis (n = 1). In all cases of abdominal thrombosis, during high resolution BMUS scan, intra-luminary hypoechogenic appositional thrombi could be detected. Meanwhile blood flow with reduced speed less than 20 cm/s could be observed by CCDS. High arterial flow speed was a sign of collateral flow changes with diffuse venous dilatation. On CEUS, changes of the microcirculation of the liver, spleen, kidneys or small bowel by infarctions or micro-emboli could be detected. In 3 cases of PV thrombosis and in 2 cases of IVC thrombosis, catheter interventions were successful performed for recanalization without relevant lumen reduction afterwards. In other cases, without interventional procedure, partial recanalization happened with venous flow speed over 15 cm/s and lumen reduction more than 50% . CONCLUSIONS: Our study highlights those thromboembolic complications can be seen in hospitalized patients with COVID-19. Multimodality ultrasound examinations is helpful for early and accurate diagnosis of these complications.

Predicting Antecedents of Employee Smart Work Adoption Using SEM-Multilayer Perceptron Approach

The COVID-19 pandemic forced many organizations to move to telework and smart work (SW), and this practice is expected to continue even later in the postpandemic period. Hence, it is very important for managers and organizations to identify the motivating and deterrent factors in adopting smart work and plan to manage them. Therefore, the present study using an innovative methodology tried to identify and prioritize the factors influencing employee SW adoption. In the first stage, the conceptual model of the research was designed, inspired by the literature. In the next step, using structural equation modeling (SEM), antecedents whose effects on employee SW adoption were confirmed were identified. Finally, the output of the SEM model was considered as the input of the multilayer perceptron (MLP) model, which is an artificial neural network model, to determine the importance of each antecedent in the prediction of employee behavior. The present study provides quantitative empirical evidence that perceived value, institutional and technological support, perceived limited communication, and perceived cost are antecedents of employee SW adoption that are, respectively, important in predicting the behavioral intentions of employees in acceptance of SW. The findings of this study contribute to both the SW and the behavioral intention theory literature. [ FROM AUTHOR]

Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2.

The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated recurring worldwide infection outbreaks. These highly mutated variants reduce the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines, which are designed to target only the spike (S) protein of the original virus. Except for the S of SARS-CoV-2, the immunoprotective potential of other structural proteins (nucleocapsid, N; envelope, E; membrane, M) as vaccine target antigens is still unclear and worthy of investigation. In this study, synthetic DNA vaccines encoding four SARS-CoV-2 structural proteins (pS, pN, pE, and pM) were developed, and mice were immunized with three doses via intramuscular injection and electroporation. Notably, co-immunization with two DNA vaccines that expressed the S and N proteins induced higher neutralizing antibodies and was more effective in reducing the SARS-CoV-2 viral load than the S protein alone in mice. In addition, pS co-immunization with either pN or pE + pM induced a higher S protein-specific cellular immunity after three immunizations and caused milder histopathological changes than pS alone post-challenge. The role of the conserved structural proteins of SARS-CoV-2, including the N/E/M proteins, should be investigated further for their applications in vaccine design, such as mRNA vaccines.

Seroepidemiology of pertussis in the east of China: Estimates of incidence of infection in adolescents and adults pre- and post-COVID-19.

Introduction: The dramatic decrease in the number of reported cases of pertussis during COVID-19 pandemic has been underestimated. The objective was to compare the estimated incidence rate of pertussis in populations pre- and post-COVID-19 pandemic by analyzing the anti-pertussis toxin (anti-PT) IgG and anti-filamentous hemagglutininant (anti-FHA) IgG antibodies in healthy Chinese population from 2018 to 2021. Methods: All serum samples (N = 1,000) were collected from healthy population (aged ≥ 15 years) who attended an annual monitoring project of antibody levels in Jiangsu province in 2018-2021 were measured by ELISA. Results: The positive rates of anti-PT IgG and anti-FHA IgG antibodies were 11.4% (114/1,000) and 20.2% (202/1,000) (≥40 IU/ml), the GMC were 17.25 (95% CI: 15.49-19.03) IU/mL and 24.94 (95% CI: 22.73-27.16) IU/mL in the study population, respectively. The percentage of participants with anti-PT IgG antibodies higher than 40 IU/mL was 5.20% (11/212) in 2018, 5.5% (19/348) in 2019, 21.2% (46/217) in 2020 and 17.0% (38/223) in 2021, respectively. The non-detectable rate (<5 IU/mL) of anti-PT IgG antibodies was 16.9, 17.7, 28.1, and 37.3% in 2018, 2019, 2020, and 2021, respectively. We assumed that the infection occurred within 58.6 days, and based on the overall proportion (2.9%) of individuals with anti-PT IgG antibody ≥100 IU/ml, the incidence rate (/100) was estimated by the formula to be 18.08 (95% CI: 12.40-26.11). In addition, the estimated incidence of Post-COVID-19 was higher than that of Pre-COVID-19 (36.33/100 vs. 12.84/100), and the difference was statistically significant (p < 0.05). Conclusions: Our results suggest a high rate of under-reporting of pertussis in Jiangsu Province both pre- and post-COVID-19 pandemic, and there are a large number of adults of childbearing age who are susceptible to pertussis. It seems imperative that vaccination of adolescents and adults should be considered for inclusion in vaccination programs.

The Incidence of Myocarditis Following an Influenza Vaccination: A Population-Based Observational Study.

BACKGROUND AND OBJECTIVE: Recently, studies have pointed to a link between coronavirus disease 2019 vaccinations and myocarditis. Myocarditis following an influenza vaccine has been sporadically reported. However, it is not known whether this adverse event occurs among elderly individuals who have received influenza vaccines. We used a population-based database and a self-controlled case-series design to estimate the incidence of myocarditis following an influenza vaccination. METHODS: Data were extracted from Taiwan's National Health Insurance Research Database. The study population consisted of elderly people aged ≥ 65 years who had de novo myocarditis, which required hospitalization, within 6 months after receiving an influenza vaccination between 2003 and 2017. The first 1-7, 1-14, and 1-42 days after vaccination were defined as risk intervals, and the other periods were defined as control intervals. Poisson regression was used to calculate the incidence rate ratio for myocarditis between the risk and control periods. RESULTS: Within 180 days following a vaccination, 191 people were hospitalized for myocarditis among 19,678,904 people. In comparison with control intervals, the incidence rate ratios of an admission for myocarditis for days 1-7, 1-14, and 1-42 were 0.80 (95% confidence interval 0.36-1.81), 0.72 (95% confidence interval 0.39-1.32), and 0.73 (95% confidence interval 0.50-1.05), respectively. Subgroup analyses by sex, age, Charlson Comorbidity Index scores, and comorbidities did not yield significant differences in the incidence rate ratio. CONCLUSIONS: Regardless of the post-vaccination time and underlying baseline characteristics, the incidence risk of myocarditis is not significantly increased in the elderly following an influenza vaccination.

External quality assessment of nucleic acid testing in provincial or municipal CDC laboratories in the COVID-19 surveillance network in China

Objective: To understand the RNA detection performance of SARS-CoV-2 Variants of Concern (VOCs) in 32 provincial or municipal CDC laboratories in COVID-19 surveillance network in China through an external quality assessment (EQA), and evaluate the clinical performance of the current SARS-CoV-2 nucleic acids detection kits used and provided by the participating laboratories.

Immunogenicity of inactivated coronavirus disease 2019 vaccines in patients with chronic hepatitis B undergoing antiviral therapy.

Objectives: To investigate the effect and its mechanisms of different antiviral agents on the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic hepatitis B (CHB). Methods: A total of 125 patients with CHB receiving nucleos(t)ide analogs (NAs) monotherapy or combined with Peg-interferon-alpha (Peg-IFNα) therapy and 29 healthy controls (HCs) were enrolled. Adverse reactions (ADRs) and levels of neutralizing antibody (NAb), immunoglobulin G (IgG), immunoglobulin M (IgM), and peripheral cytokines post-vaccination were analyzed. Results: All ADRs were tolerable in CHB patients. Overall, no significant difference was observed in the antibody levels between patients and HCs after two doses of vaccination. An inverse correlation between NAb, IgG titers and the days after two doses was found in non-IFN group but not in IFN group. Correspondingly, peripheral interferon-γ levels were significantly higher in IFN group than in non-IFN group. After a booster dose, NAb and IgG antibodies were maintained at high levels in NA-treated patients. Conclusion: Peg-interferon-alpha-based therapy may be beneficial for maintaining the immunogenicity of SARS-CoV-2 vaccines in CHB patients, which may be related to the high levels of IFN-γ induced by Peg-IFNα therapy. A booster dose can effectively recall the robust and long-lasting immunogenicity of SARS-CoV-2 vaccines.

Managing Risk in Dynamic Conditions: Emerging Crises, Changing Technologies, and the Collective Capacity to Learn

Governing unexpected, extreme events requires a fundamental change in the design of planning processes and responsibilities to enable communities to manage novel risks in sustainable ways. The challenge is to create continuous learning processes for communities that include participants at diverse levels of knowledge, skill, vulnerability, and commitment to reducing risk not only for themselves, but for the whole community. To investigate the problem of collective learning under stress, we analyzed processes of organizational learning in the operational context of Taiwan over a series of extreme events, 1999-2020. While collective learning did occur in Taiwan, it is not clear that sustainable management of novel risks has been achieved. Finding the balance between social coherence and system control likely needs to be recalibrated for each new event.

Multisystem inflammatory syndrome (MIS-C) with SARS-CoV-2 omicron variant BA.2.38 in a four-year-old Chinese girl: A case report.

We report a severe COVID-19 complicated with MIS-C in a girl treated by the author in China, and discuss the current research status and progress in the diagnosis and therapy of MIS-C in children. The patient was a 4-year-old child previously healthy who was referred to the hospital with a complaint of fever, finally, Multisystem inflammatory syndrome was diagnosed with COVID-19.

Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review.

Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.

Boosting the detection performance of severe acute respiratory syndrome coronavirus 2 test through a sensitive optical biosensor with new superior antibody.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in late 2019 leading to the COVID-19 disease pandemic that triggered socioeconomic turmoil worldwide. A precise, prompt, and affordable diagnostic assay is essential for the detection of SARS-CoV-2 as well as its variants. Antibody against SARS-CoV-2 spike (S) protein was reported as a suitable strategy for therapy and diagnosis of COVID-19. We, therefore, developed a quick and precise phase-sensitive surface plasmon resonance (PS-SPR) biosensor integrated with a novel generated anti-S monoclonal antibody (S-mAb). Our results indicated that the newly generated S-mAb could detect the original SARS-CoV-2 strain along with its variants. In addition, a SARS-CoV-2 pseudovirus, which could be processed in BSL-2 facility was generated for evaluation of sensitivity and specificity of the assays including PS-SPR, homemade target-captured ELISA, spike rapid antigen test (SRAT), and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Experimentally, PS-SPR exerted high sensitivity to detect SARS-CoV-2 pseudovirus at 589 copies/ml, with 7-fold and 70-fold increase in sensitivity when compared with the two conventional immunoassays, including homemade target-captured ELISA (4 × 103 copies/ml) and SRAT (4 × 104 copies/ml), using the identical antibody. Moreover, the PS-SPR was applied in the measurement of mimic clinical samples containing the SARS-CoV-2 pseudovirus mixed with nasal mucosa. The detection limit of PS-SPR is calculated to be 1725 copies/ml, which has higher accuracy than homemade target-captured ELISA (4 × 104 copies/ml) and SRAT (4 × 105 copies/ml) and is comparable with qRT-PCR (1250 copies/ml). Finally, the ability of PS-SPR to detect SARS-CoV-2 in real clinical specimens was further demonstrated, and the assay time was less than 10 min. Taken together, our results indicate that this novel S-mAb integrated into PS-SPR biosensor demonstrates high sensitivity and is time-saving in SARS-CoV-2 virus detection. This study suggests that incorporation of a high specific recognizer in SPR biosensor is an alternative strategy that could be applied in developing other emerging or re-emerging pathogenic detection platforms.

Immunomolecular assay based on selective virion capture by spike antibody and viral nucleic acid amplification for detecting intact SARS-CoV-2 particles.

BACKGROUND: Effective therapeutics and vaccines for coronavirus disease 2019 (COVID-19) are currently lacking because of the mutation and immune escape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on the propagation characteristics of SARS-CoV-2, rapid and accurate detection of complete virions from clinical samples and the environment is critical for assessing infection risk and containing further COVID-19 outbreaks. However, currently applicable methods cannot achieve large-scale clinical application due to factors such as the high viral load, cumbersome virus isolation steps, demanding environmental conditions, and long experimental periods. In this study, we developed an immuno molecular detection method combining capture of the viral spike glycoprotein with monoclonal antibodies and nucleic acid amplification via quantitative reverse transcription PCR to rapidly and accurately detect complete virions. RESULTS: After constructing a novel pseudovirus, screening for specific antibodies, and optimizing the detection parameters, the assay achieved a limit of detection of 9 × 102 transduction units/mL of viral titer with high confidence (~ 95%) and excellent stability against human serum and common virus/pseudovirus. The coefficients of variation were 1.0 ~ 2.0% for intra-assay and inter-assay analyses, respectively. Compared with reverse transcription-PCR, the immunomolecular method more accurately quantified complete virions. SARS-CoV-2/pseudovirus was more stable on plastic and paper compared with aluminum and copper in the detection of SARS-CoV-2 pseudovirus under different conditions. Complete virions were detected up to 96 h after they were applied to these surfaces (except for copper), although the titer of the virions was greatly reduced. CONCLUSION: Convenient, inexpensive, and accurate complete virus detection can be applied to many fields, including monitoring the infectivity of convalescent and post-discharge patients and assessing high-risk environments (isolation rooms, operating rooms, patient living environments, and cold chain logistics). This method can also be used to detect intact virions, including Hepatitis B and C viruses, human immunodeficiency virus, influenza, and the partial pulmonary virus, which may further improve the accuracy of diagnoses and facilitate individualized and precise treatments.

Chlorination of isothiazolinone biocides: kinetics, reactive species, pathway, and toxicity evolution.

Due to the Covid-19 pandemic, the worldwide biocides application has been increased, which will eventually result in enhanced residuals in treated wastewater. At the same time, chlorine disinfection of secondary effluents and hospital wastewaters has been intensified. With respect to predicted elevated exposure in wastewater, the chlorination kinetics, transformation pathways and toxicity evolution were investigated in this study for two typical isothiazolinone biocides, methyl-isothiazolinone (MIT) and chloro-methyl-isothiazolinone (CMIT). Second-order rate constants of 0.13 M-1·s-1, 1.95 × 105 M-1·s-1 and 5.14 × 105 M-1·s-1 were determined for the reaction of MIT with HOCl, Cl2O and Cl2, respectively, while reactivity of CMIT was around 1-2 orders of magnitude lower. While chlorination of isothiazolinone biocides at pH 7.1 was dominated by Cl2O-oxidation, acidic pH and elevated Cl- concentration favored free active chlorine (FAC) speciation into Cl2 and increased overall isothiazolinone removal. Regardless of the dominant FAC species, the elimination of MIT and CMIT resulted in an immediate loss of acute toxicity under all experimental conditions, which was attributed to a preferential attack at the S-atom resulting in subsequent formation of sulfoxides and sulfones and eventually an S-elimination. However, chlorination of isothiazolinone biocides in secondary effluent only achieved <10% elimination at typical disinfection chlorine exposure 200 mg·L-1·min, but was predicted to be remarkably increased by acidizing solution to pH 5.5. Alternative measures might be needed to minimize the discharge of these toxic chemicals into the aquatic environment.

Coronaviruses in wild animals sampled in and around Wuhan at the beginning of COVID-19 emergence.

Over the last several decades, no emerging virus has had a profound impact on the world as the SARS-CoV-2 that emerged at the end of 2019 has done. To know where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated from and how it jumped into human population, we immediately started a surveillance investigation in wild mammals in and around Wuhan when we determined the agent. Herein, coronaviruses were screened in the lung, liver, and intestinal tissue samples from fifteen raccoon dogs, seven Siberian weasels, three hog badgers, and three Reeves's muntjacs collected in Wuhan and 334 bats collected around Wuhan. Consequently, eight alphacoronaviruses were identified in raccoon dogs, while nine betacoronaviruses were found in bats. Notably, the newly discovered alphacoronaviruses shared a high whole-genome sequence similarity (97.9 per cent) with the canine coronavirus (CCoV) strain 2020/7 sampled from domestic dog in the UK. Some betacoronaviruses identified here were closely related to previously known bat SARS-CoV-related viruses sampled from Hubei province and its neighbors, while the remaining betacoronaviruses exhibited a close evolutionary relationship with SARS-CoV-related bat viruses in the RdRp gene tree and clustered together with SARS-CoV-2-related bat coronaviruses in the M, N and S gene trees, but with relatively low similarity. Additionally, these newly discovered betacoronaviruses seem unlikely to bind angiotensin-converting enzyme 2 because of the deletions in the two key regions of their receptor-binding motifs. Finally, we did not find SARS-CoV-2 or its progenitor virus in these animal samples. Due to the high circulation of CCoVs in raccoon dogs in Wuhan, more scientific efforts are warranted to better understand their diversity and evolution in China and the possibility of a potential human agent.

Response of Scalp and Skull Metastasis to Anti-PD-1 Antibody Combined with Regorafenib Treatment in a Sorafenib-Resistant Hepatocellular Carcinoma Patient and a Literature Review.

Background: Scalp and skull metastasis of hepatocellular carcinoma (HCC) is extremely rare. Modalities for the treatment of this disease include craniotomy, radiotherapy and chemotherapy, which are unsatisfactory. We report a case of HCC with scalp and skull metastasis and review similar cases from the literature to accumulate experience for better management of this type of HCC metastasis. Case Presentation: A 54-year-old female was diagnosed with advanced HCC with posterior portal vein tumor thrombus (PVTT) at admission. She received laparoscopic microwave therapy for a large tumor in Segment 6, which was then followed by sorafenib therapy. One year later, sorafenib resistance developed, metastasis occurred in the scalp and skull, left sacroiliac joint, and lung; PVTT extended into the main portal vein and alpha-feta protein (AFP) levels exceeded 65,000 ng/mL. Systemic therapy was then substituted by regorafenib combined with sintilimab. Three months later, AFP decreased to 2005 ng/mL; meanwhile, skull and lung metastatic lesions shrank significantly. Furthermore, both lump and limp disappeared. One year after the combination of regorafenib and sintilimab, skull and lung metastasis, and PVTT were completely relieved. Moreover, primary liver lesions showed no sign of activity. With comprehensive therapy, the patient has survived for 5 years and 7 months. Conclusion: Sorafenib-regorafenib sequential treatment combined with sintilimab is safe and effective when used to treat HCC skull metastasis, for which high-level evidence is needed to support this treatment strategy.

Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors.

The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CLpro) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8H-indeno[1,2-d]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CLpro. Among them, the representative compound 7a displayed inhibitory activity with an IC50 of 1.28 ± 0.17 µM against SARS-CoV-2 3CLpro. Molecular docking of 7a against 3CLpro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CLpro.

Impact of COVID-19 Pandemic on Elevated Anxiety Symptoms of Maintenance Hemodialysis Patients in China: A One-Year Follow-Up Study.

Recent studies have shown that coronavirus disease 2019 (COVID-19) aggravates anxiety in patients with maintenance hemodialysis (MHD), but it is still unclear how long this adverse effect will last. This study aims to investigate the impact of COVID-19 on the elevated anxiety symptoms of MHD patients 1 year after the outbreak. Assessment of elevated anxiety symptoms was performed on patients with MHD during early COVID-19 (February 17-February 29, 2020) and 1-year follow-up (March 1-March 13, 2021), and a total of 100 patients had completed face-to-face questionnaires at the first and 1-year follow-up. At the beginning of the outbreak, 40% of the patients with MHD had anxiety symptoms [self-rating anxiety scale (SAS) score ≥ 50], and 11% (SAS score: 60-69) and 2% (SAS score ≥ 70) of the patients had moderate and severe anxiety symptoms, respectively. Multivariate analysis shows that possibility of unaccompanied transfer, possibility of family members or themselves being infected in a hospital, added body temperature monitoring during dialysis, and increased medical procedures are the risk factors in elevated anxiety symptoms during early COVID-19. At the 1-year follow-up, the incidence of anxiety symptoms in the same group of patients declined to 28%, and all the patients had mild anxiety symptoms (SAS score: 50-59), which is significantly lower than that of the early COVID-19 pandemic with statistically significant difference (p = 0.003). Increased protective measures taken by the medical staves were the only risk factor in elevated anxiety symptoms during the 1-year follow-up. This study shows that COVID-19 has a direct impact on the deterioration of anxiety symptoms in patients with MHD. With the changes of the requirements for COVID-19 prevention and control, as well as the enhancement of propaganda and education of the pandemic and psychological care, the severity and risk factors of anxiety symptoms in the patients with MHD are changing. Thus, targeted interventions are suggested to improve the psychological endurance of the patients with MHD.