Discovery of dual S-RBD/NRP1-targeting peptides: structure-based virtual screening, synthesis, biological evaluation, and molecular dynamics simulation studies.

Both receptor-binding domain in spike protein (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human neuropilin-1 (NRP1) are important in the virus entry, and their concomitant inhibition may become a potential strategy against the SARS-CoV-2 infection. Herein, five novel dual S-RBD/NRP1-targeting peptides with nanomolar binding affinities were identified by structure-based virtual screening. Particularly, RN-4 was found to be the most promising peptide targeting S-RBD (Kd = 7.4 ± 0.5 nM) and NRP1-BD (the b1 domain of NRP1) (Kd = 16.1 ± 1.1 nM) proteins. Further evidence in the pseudovirus infection assay showed that RN-4 can significantly inhibit the SARS-CoV-2 pseudovirus entry into 293 T cells (EC50 = 0.39 ± 0.09 µM) without detectable side effects. These results suggest that RN-4, a novel dual S-RBD/NRP1-targeting agent, holds potential as an effective therapeutic to combat the SARS-CoV-2 infection.

Framework for virtual education of COVID-19 vaccines for Mandarin-speaking learners: an educational intervention module

Background: In the United States, patients with limited English proficiency face significant barriers to comprehending and acting upon health-related information, particularly during the COVID-19 pandemic. The ability of health professionals to communicate COVID-19-related information to Mandarin-speaking patients has proved critical in discussions about vaccine efficacy, side effects, and post-vaccine protection. Methods: The authors created a one-hour educational module to help Mandarin-speaking medical students better convey COVID-19 vaccine information to Mandarin-only speakers. The module is composed of an educational guide, which introduced key terminology and addressed commonly asked questions, and pre- and post-surveys. The authors recruited 59 Mandarin-speaking medical students all of whom had previously completed a medical Mandarin elective. The module and surveys were distributed and completed in August 2021. Data analysis measured the change in aggregate mean for subjective five-point Likert-scale questions and change in percent accuracy for objective knowledge-based questions. Results: The educational module significantly improved participants' subjective comfort level in discussing the COVID-19 vaccine in English and Mandarin. The largest improvement in both English and Mandarin was demonstrated in the participants ability to explain differences between the COVID-19 vaccines, with an aggregate mean improvement of 0.39 for English and 1.48 for Mandarin. Survey respondents also demonstrated increased percent accuracy in knowledge-based objective questions in Mandarin. Conclusions: This module provides Mandarin-learning medical students with skills to deliver reliable information to the general population and acts as a model for the continued development of educational modules for multilingual medical professionals.

Increases in CLIA-Waived Testing Sites Since the Start of the COVID-19 Pandemic.

The number of testing sites receiving their first Certificate of Waiver (CoW) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) increased significantly after the start of the COVID-19 pandemic. We compared the first-time CoWs in 2020-2021 to those in 2018-2019. The total number of first-time CoWs during 2020-2021 was more than twice what it was in 2018-2019, corresponding to population testing needs during the COVID-19 pandemic, especially in assisted living facility, pharmacy, physician office, and school/student health service settings. This study highlighted the need to strengthen clinical testing strategies to be better prepared for future public health emergencies.

Whole genome sequence analysis of SARS-CoV-2 from 40 imported cases of confirmed COVID-19 in Sichuan

Objective To understand the genomic characteristics of SARS-CoV-2 from 40 imported cases with confirmed COVID-19 in Sichuan during January and March 2022. Methods Total viral RNA was extracted from respiratory samples of 182 confirmed COVID-19 cases who entered China through Chendu International Airport from January to March 2022.Mutation nucleic acid detection kit was used to identify the mutant strains and Illumina sequencing platform was applied for whole genome sequence（WGS） of virus.SARS-CoV-2 reference sequences were downloaded from NCBI database for genetic evolution and antigen variation analysis.The Nextclade and Pangolin online virus analysis platform were used to determine the virus family and type,and to analyze the mutation loci of the virus.The phylogenetic tree was constructed,along with the epidemiological data of cases to analyze the source and correlation of viruses. Results Among 182 imported COVID-19 cases,B.1.617.2 mutations were identified in 3 cases and B.1.1.529 mutations were detected in 57 cases.A total of 40 SARS-CoV-2 whole genome sequences with coverage>95% were obtained in this study.Nextclade typing analysis showed that 3 sequences belonged to 21J（Delta）,5 sequences belonged to 21K（Omicron）and the remaining 32 sequences belonged to 21L（Omicron）.Pangolin typing analysis showed that the 3 sequences of 21J（Delta）belonged to AY.4,AY.109and B.1.617.2,the 5sequences of 21K（Omicron）all belonged to BA.1.1,and the remaining 32 sequences of 21L（Omicron）belonged to BA.2.Our sequence results were99.7% consistency with the Omicron variants sequences in current GISAID database.Compared with the reference sequence strain Wuhan-Hu-1（NC＿045512.2）,45,47and 42nucleotide variation sites and 36,25 and 36amino acid variation sites were found in the 3 sequences of 21J（Delta）.There were average 59（26-64）nucleotide mutation sites and 48（10-53）amino acid mutation sites in the 5sequences of 21K（Omicron）.The median number of nucleotide mutation sites of 71（66-76）and amino acid mutation sites of 53（40-56）were identified in the 32sequences of 21L（Omicron）.Phylogenetic tree analysis showed that 40SARS-CoV-2WGSs were all related to the current variants of concern（VOC）. Conclusions Continuous sequencing of SARS-CoV-2whole genome from imported cases with confirmed COVID-19is of great significance for the prevention and control of the outbreak and prevalence of local epidemic caused by imported viruses in Sichuan.

Association Between Clinical Competencies and Mental Health Symptoms Among Frontline Medical Staff During the COVID-19 Outbreak: A Cross-Sectional Study.

Background: In China, mental health of frontline medical staff might be influenced by clinicians' ability to handle the outbreak of coronavirus disease 2019 (COVID-19). Few studies to-date have addressed the association between clinicians' competencies and mental health in this context. This cross-sectional study was to examine the prevalence of mental health symptoms among frontline medical staff that fought against the COVID-19 outbreak, and explore the associations between their competencies, and separate and concurrent depressive and anxiety symptoms. Methods: A total of 623 frontline medical staff was included in this study. Competencies, depressive symptoms, and anxiety symptoms were assessed using a self-reported short form of the Chinese clinical physicians' competency model, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 questionnaire, respectively. Logistic regression models were used to evaluate the associations between one SD increase in competency scores and the prevalence of mental health problems. Results: The prevalence of depressive, anxiety, and comorbid depressive and anxiety symptoms was 40.93, 31.78, and 26.00%, respectively. Among the medical staff with higher total competency scores, the prevalence of depressive [odds ratios (ORs) = 0.67, 95% confidence intervals (CIs): 0.55-0.81], anxiety (OR = 0.68, 95% CI: 0.56-0.83), and comorbid anxiety and depressive symptoms (OR = 0.69, 95% CI: 0.55-0.83) was lower than among their lower-scoring counterparts. Subgroup analyses stratified by core competency scores revealed similar associations as the main analyses. Conclusion: The present findings highlight the association between high core competency scores and lower prevalence of depressive, anxiety, and comorbid anxiety and depressive symptoms.

Gastrointestinal Symptoms Are Associated with Increased Risk of Progression from Non- severe to Severe Illness in COVID-19 Patients (preprint)

BackgroundThe involvement of gastrointestinal (GI) symptoms in the progression of illness in COVID-19 patients has not been illustrated, with the association between GI symptoms and illness severity remaining controversial. The present study aimed to evaluate the association between GI symptoms and the illness progression, severity, and prognosis in COVID-19 patients.MethodsThis study retrospectively recruited consecutive patients with laboratory-confirmed COVID-19 from three hospitals in Wuhan. The severity of illness was classified as non-severe and severe for analyses. The primary outcome was the association between GI symptoms and progression from non-severe to severe illness (PNTS) in COVID-19 patients. ResultsOf the 934 COVID-19 patients (mean age 59.3 years; 43.7% males), the prevalence of overall and specific GI symptoms at/prior to admission were 59.9% and 13.0%, respectively. Patients with GI symptoms were associated with increased risk of fever (56.1% vs. 48.1%; P=0.02), increased IL-6 (18.2% vs. 11.7%; P=0.04), ground-glass opacity (56.8% vs. 43.1%; P<0.001), bilateral pneumonia (80.4% vs. 72.3%; P=0.005), secondary infections (12.6% vs. 6.5%;, P=0.003), and hypoalbuminemia (26.2% vs. 18.4%; P=0.01). Patients with GI symptoms had a higher risk for PNTS (2.9% vs. 0.6%; P=0.02), even after full adjustments (OR, 6.50; (95%CI:1.34-31.6); P=0.02), but comparable risk for severe illness or deaths. GI symptoms and the specific GI symptoms were identified as the independent risk factors for PNTS.Conclusions The occurrence of GI symptoms is proved to be an independent risk factor for PNTS, which might be a predicting indicator in the prevention of illness deterioration at an early stage.

The occurrence and risk factors associated with post-traumatic stress disorder among discharged COVID-19 patients in Tianjin, China.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a serious mental health condition that is triggered by a terrifying event. We aimed to investigate the occurrence and risk factors of PTSD among discharged COVID-19 patients. METHODS: This study included 144 discharged COVID-19 patients. PTSD was assessed by using validated cut-offs of the impact of event scale-revised (IES-R, score ≥25). All patients completed a detailed questionnaire survey, and clinical parameters were routinely measured in the hospital. Binary logistic regression models were applied to identify factors associated with PTSD. RESULTS: Of the 144 participants with laboratory-confirmed COVID-19, the occurrence of PTSD was 16.0%. In multivariable analyses, age above 40 years (adjusted OR [95% CI], 5.19 [2.17-12.32]), female sex (adjusted OR [95% CI], 7.82 [3.18-18.21]), current smoker (adjusted OR [95% CI], 6.72 [3.23-15.26]), and ≥3 involved pulmonary lobes (adjusted OR [95% CI], 5.76 [1.19-15.71]) were significantly associated with a higher risk of PTSD. Conversely, history of hypertension and serum hemoglobin levels were significantly associated with a lower risk of PTSD with adjusted ORs (95% CI) of 0.37 (0.12-0.87) and 0.91 (0.82-0.96), respectively. CONCLUSION: Old age, gender (being female), current smoking, bacterial pneumonia, and ≥3 involved pulmonary lobes were associated with an increased occurrence of PTSD among discharged COVID-19 patients.

Clinical characteristics of COVID-19 patients with complications: implications for management.

BACKGROUND: A novel coronavirus disease 2019 (COVID-19) has caused outbreaks worldwide, and the number of cases is rapidly increasing through human-to-human transmission. Because of the greater transmission capacity and possible subsequent multi-organ damage caused by the virus, it is crucial to understand precisely and manage COVID-19 patients. However, the underlying differences in the clinical features of COVID-19 with and without comorbidities are not fully understood. AIM: The objective of this study was to identify the clinical features of COVID-19 patients with and without complications to guide treatment and predict the prognosis. METHOD: We collected the clinical characteristics of COVID-19 patients with and without different complications, including hypertension, cardiovascular disease and diabetes. Next, we performed a baseline comparison of each index and traced the dynamic changes in these factors during hospitalization to explore the potential associations. RESULT: A clinical index of differential expression was used for the regression to select top-ranking factors. The top-ranking clinical characteristics varied in each subgroup, such as indices of liver function, renal function and inflammatory markers. Among them, the indices of renal function were highly ranked in all subgroups and displayed significant differences during hospitalization. CONCLUSION: Organ functions of COVID-19 patients, particularly renal function, should be cautiously taken care of during management and might be a crucial factor for a poor prognosis of these patients with complications.

A rapid screening classifier for diagnosing COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) has caused a global pandemic. A classifier combining chest X-ray (CXR) with clinical features may serve as a rapid screening approach. Methods: The study included 512 patients with COVID-19 and 106 with influenza A/B pneumonia. A deep neural network (DNN) was applied, and deep features derived from CXR and clinical findings formed fused features for diagnosis prediction. Results: The clinical features of COVID-19 and influenza showed different patterns. Patients with COVID-19 experienced less fever, more diarrhea, and more salient hypercoagulability. Classifiers constructed using the clinical features or CXR had an area under the receiver operating curve (AUC) of 0.909 and 0.919, respectively. The diagnostic efficacy of the classifier combining the clinical features and CXR was dramatically improved and the AUC was 0.952 with 91.5% sensitivity and 81.2% specificity. Moreover, combined classifier was functional in both severe and non-serve COVID-19, with an AUC of 0.971 with 96.9% sensitivity in non-severe cases, which was on par with the computed tomography (CT)-based classifier, but had relatively inferior efficacy in severe cases compared to CT. In extension, we performed a reader study involving three experienced pulmonary physicians, artificial intelligence (AI) system demonstrated superiority in turn-around time and diagnostic accuracy compared with experienced pulmonary physicians. Conclusions: The classifier constructed using clinical and CXR features is efficient, economical, and radiation safe for distinguishing COVID-19 from influenza A/B pneumonia, serving as an ideal rapid screening tool during the COVID-19 pandemic.

Etiology of Severe Community-Acquired Pneumonia in Adults Based on Metagenomic Next-Generation Sequencing: A Prospective Multicenter Study.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) has the potential to improve the pathogen identification in severe community-acquired pneumonia (SCAP). METHODS: In this 1.5-year, multicenter, prospective study, we investigated the usefulness of mNGS of BALF for identifying pathogens of SCAP in hospitalized adults, comparing it with other laboratory methods. RESULTS: Of 329 SCAP adults, a microbial etiology was established in 304 cases (92.4%). The overall microbial yield was 90.3% for mNGS versus 39.5% for other methods (P < 0.05). The most frequently detected pathogens in immunocompetent patients were Streptococcus pneumoniae (14.8%), rhinovirus (9.8%), Haemophilus influenzae (9.1%), Staphylococcus aureus (8.7%), and Chlamydia psittaci (8.0%), while in immunocompromised patients they were Pneumocystis jirovecii (44.6%), Klebsiella pneumoniae (18.5%), Streptococcus pneumoniae (15.4%), Haemophilus influenzae (13.8%), and Pseudomonas aeruginosa (13.8%). Notably, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified from two patients solely by mNGS in January 2020; uncommon pathogens including Orientia tsutsugamushi and Nocardia otitidiscaviarum were identified from one patient, respectively. Furthermore, mixed infections were detected in 56.8% of the patients. CONCLUSIONS: A high microbial detection rate was achieved in SCAP adults using mNGS testing of BALF. The most frequently detected pathogens of SCAP differed between immunocompetent and immunocompromised patients. mNGS testing may be an powerful tool for early identification of potential pathogens for SCAP to initiate a precise antimicrobial therapy.

Gastrointestinal Symptoms Are Associated with the Increased Risk of Progression from Non-Severe to Severe Illness in COVID-19 Patients: A Multicenter, Retrospective Study (preprint)

Background: The involvement of gastrointestinal (GI) symptoms in the progression of COVID-19 patients has not been illustrated, with the association between GI symptoms and severity of illness remaining controversial. The present study aimed to evaluate the association between GI symptoms and the illness progression, severity, and prognosis of COVID-19 patients. Design: This retrospective study recruited 1024 consecutive patients with laboratory-confirmed COVID-19 from three hospitals in Wuhan. The severity of illness was classified as non-severe and severe for analyses. The primary outcome was the association between GI symptoms and the progression from non-severe to severe illness (PNTS) in COVID-19 patients. Results: Of the 934 COVID-19 patients (mean age 59.3 years; 43.7% males), the prevalence of overall and specific GI symptoms at/prior to admission were 59.9% and 13.0%, respectively. Patients with GI symptoms were associated with increased risk of fever (56.1% vs. 48.1%; P=0.02), increased IL-6 (18.2% vs. 11.7%; P=0.04), ground-glass opacity (56.8% vs. 43.1%; P<0.001), bilateral pneumonia (80.4% vs. 72.3%; P=0.005), secondary infections (12.6% vs. 6.5%;, P=0.003), and hypoalbuminemia (26.2% vs. 18.4%; P=0.01). Patients with GI symptoms had a higher risk for PNTS (2.9% vs. 0.6%; P=0.02), even after full adjustments (OR, 6.50; (95%CI:1.34-31.6); P=0.02), but no risk for severe illness or deaths. GI symptoms and the specific GI symptoms were identified as the independent risk factors for PNTS. Conclusion: The occurrence of GI symptoms is proved to be the independent risk factor for PNTS, which might be a crucial indicator in the early prevention of illness deterioration.Funding Statement: National Key R&D Program of China (2018YFC1313103), and National Natural Science Foundation of China (Grant No. 81670473 and 81873546), "Shu Guang" project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 19SG30).Declaration of Interests: There is no conflict of interests for each authorEthics Approval Statement: This study was approved by the Ethics Committee of the Changhai hospitals. The requirement for informed patient consent was waived by the ethics committee due to the retrospective design and as the data analyzed were considered as a part of a continuing investigation of a public health emergency of international concern by the National Health Commission (NHC) of the People's Republic of China.

The proportion and effect of corticosteroid therapy for patients with COVID-19 infection: a systematic review and meta-analysis (preprint)

Objectives: COVID-19 remains a global challenge. Corticosteroids are a group of anti-inflammatory and suppressive immune response drugs that are widely used in the treatment of COVID-19, especially when it presents with viral pneumonia. Comprehensive reviews investigating the comparative proportion and efficacy of corticosteroid use are scarce. Therefore, we conducted a systematic review and meta-analysis of clinical trials to evaluate the proportion and efficacy of corticosteroid use for the treatment of COVID-19.Methods: We conducted a comprehensive literature review of PubMed, EMBASE, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Database for relevant trials on glucocorticoid therapy in COVID-19 patients. Outcome measures were the proportion of patients administered corticosteroids, viral clearance and mortality. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with associated 95% confidence intervals (CIs).Results: Forty-three trials involving 6603 patients were included. The meta-analysis demonstrated that the proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. In addition, our meta-analysis demonstrated no significant difference in the proportions of severe and nonsevere patients who were administered corticosteroids. We also performed subgroup analyses stratified by severity, indicating that the proportion of patients administered corticosteroids was significantly higher among intensive care unit (ICU) patients than among non-ICU patients. The results of our meta-analysis indicated that corticosteroid treatment significantly delayed the viral clearance time. Finally, our meta-analysis demonstrated no significant difference between the use of corticosteroids for COVID-19 patients who died and those who survived. This result indicated that mortality was not correlated with corticosteroid therapy.Conclusion: The proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. Corticosteroid use in subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections delayed virus clearance and did not convincingly improve survival;therefore, corticosteroids should be used with caution in the treatment of COVID-19.

[Analysis of 131 cases of COVID-19 treated with Ganlu Xiaodu Decoction].

In this study, Donghua Hospital information management system and Meikang clinical pharmacy management system were used to collect medical records of all inpatients diagnosed as coronavirus disease 2019(COVID-19) in Wuhan Third Hospital. The statistics was based on the data of the cases treated with Ganlu Xiaodu Decoction, including demographic statistics, clinical cha-racteristics before medication, outcome of after medication and efficacy of drug combination. Excel 2003 and SPSS Clementine 12.0 software were used to conduct statistics on the included cases, and Apriori algorithm and association rules were used for the association analysis on drug combination. A total of 131 cases of COVID-19 were treated with Ganlu Xiaodu Decoction combined with Chinese and Western medicine. All of the patients were cured and discharged. The drug combination mainly included Ganlu Xiaodu Decoction, abidor, Lianhua Qingwen, moxifloxacin, Qiangli Pipa Lu, vitamin C, glycyrrhizinate diammonium, pantoprazole and Shufeng Jiedu. There is a certain regularity and effectiveness in the treatment of COVID-19 infection patients with the combination of Ganlu Xiaodu Decoction and other drugs, but the rationality and safety still need to be further verified.