Evaluation of a high-sensitivity SARS-CoV-2 antigen test on the fully automated light-initiated chemiluminescent immunoassay platform.

OBJECTIVES: To describe a high-sensitivity SARS-CoV-2 antigen test that is based on the fully automated light-initiated chemiluminescent immunoassay (LiCA®), and to validate its analytical characteristics and clinical agreement on detecting SARS-CoV-2 infection against the reference molecular test. METHODS: Analytical performance was validated and detection limits were determined using different types of nucleocapsid protein samples. 798-pair anterior nasal swab specimens were collected from hospitalized patients and asymptomatic screening individuals. Agreement between LiCA® antigen and real-time reverse transcription polymerase chain reaction (rRT-PCR) was evaluated. RESULTS: Repeatability and within-lab precision were 1.6-2.3%. The C5∼C95 interval was -5.1-4.6% away from C50. Detection limits in average (SD) were 325 (±141) U/mL on the national reference panel, 0.07 (±0.04) TCID50/mL on active viral cultures, 0.27 (±0.09) pg/mL on recombinant nucleocapsid proteins and 1.07 (±1.01) TCID50/mL on inactivated viral suspensions, respectively. LiCA detected a median of 374-fold (IQR 137-643) lower levels of the viral antigen than comparative rapid tests. As reference to the rRT-PCR method, overall sensitivity and specificity were determined to be 97.5% (91.4-99.7%) and 99.9% (99.2-100%), respectively. Total agreement between both methods was 99.6% (98.7-99.9%) with Cohen's kappa 0.98 (0.96-1). A positive detection rate of 100% (95.4-100%) was obtained as Ct≤37.8. CONCLUSIONS: The LiCA® system provides an exceptionally high-sensitivity and fully automated platform for the detection of the SARS-CoV-2 antigen in nasal swabs. The assay may have high potential use for large-scale population screening and surveillance of COVID-19 as an alternative to the rRT-PCR test.

Nucleic acid strategies for infectious disease treatments: The nanoparticle-based oral delivery route.

Therapies based on orally administrated nucleic acids have significant potential for the treatment of infectious diseases, including chronic inflammatory diseases such as inflammatory bowel disease (IBD)-associated with the gastrointestinal (GI) tract, and infectious and acute contagious diseases like coronavirus disease 2019 (COVID-19). This is because nucleic acids could precisely regulate susceptibility genes in regulating the pro- and anti-inflammatory cytokines expression related to the infections. Unfortunately, gene delivery remains a major hurdle due to multiple intracellular and extracellular barriers. This review thoroughly discusses the challenges of nanoparticle-based nucleic acid gene deliveries and strategies for overcoming delivery barriers to the inflammatory sites. Oral nucleic acid delivery case studies were also present as vital examples of applications in infectious diseases such as IBD and COVID-19.

Effect of SARS-CoV-2 infection on asthma patients

Background SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), a new coronavirus pneumonia, and containing such an international pandemic catastrophe remains exceedingly difficult. Asthma is a severe chronic inflammatory airway disease that is becoming more common around the world. However, the link between asthma and COVID-19 remains unknown. Through bioinformatics analysis, this study attempted to understand the molecular pathways and discover potential medicines for treating COVID-19 and asthma. Methods To investigate the relationship between SARS-CoV-2 and asthma patients, a transcriptome analysis was used to discover shared pathways and molecular signatures in asthma and COVID-19. Here, two RNA-seq data (GSE147507 and GSE74986) from the Gene Expression Omnibus were used to detect differentially expressed genes (DEGs) in asthma and COVID-19 patients to find the shared pathways and the potential drug candidates. Results There were 66 DEGs in all that were classified as common DEGs. Using a protein-protein interaction (PPI) network created using various bioinformatics techniques, five hub genes were found. We found that asthma has some shared links with the progression of COVID-19. Additionally, protein-drug interactions with common DEGs were also identified in the datasets. Conclusion We investigated possible links between COVID-19 and asthma using bioinformatics databases, which might be useful in treating COVID-19 patients. More studies on populations affected by these diseases are needed to elucidate the molecular mechanism behind their association.

Sociodemographic and Psychological Predictors of Resilience Among Frontline Nurses Fighting the COVID-19 Pandemic.

OBJECTIVE: According to a WHO report, the number of patients with coronavirus disease 2019 (COVID-19) has reached 456,797,217 worldwide as of 15 March, 2022. In Wuhan, China, large teams of health-care personnel were dispatched to respond to the COVID-19 emergency. This study aimed to determine the sociodemographic and psychological predictors of resilience among frontline nurses fighting the current pandemic. METHODS: A total of 143 nurses were recruited from February 15 to February 20, 2020, to participate in this study. The 10-item Connor-Davidson Resilience Scale and the 21-item Depression Anxiety Stress Scale were used to estimate the participants' resilience and mental wellbeing. RESULTS: Results showed that the nurses displayed a moderate resilience level. Their median depression, anxiety, and stress scores were 1, 2, and 3, respectively, which were negatively correlated with resilience. Female gender, being dispatched to Wuhan, and depression levels were the significant predictors of resilience. CONCLUSIONS: The results suggest that particular attention should be given to nurses who were dispatched to Wuhan and who exhibited depression symptoms, and appropriate measures should be taken to boost their resilience.

A high potent synthetic nanobody with broad-spectrum activity neutralizes SARS-Cov-2 virus and Omicron variant through a unique binding mode (preprint)

COVID-19 continues to be a severe public health thread worldwide. The major challenge to control this pandemic is the rapid mutation rate of the SARS-Cov-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is pivotal to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-Cov-2 variants. In this study, we first got a synthetic nanobody (named C5) which could interfere with ACE2 binding to SARS-Cov-2 spike protein and its RBD domain. The affinity matured format of C5 clone, named C5G2, has a single digit nanomolar affinity to RBD domain and inhibit its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assay indicated that the monovalent C5G2 could protect the cells from the infection of SARS-Cov-2 wild type virus as well as most of the virus of concern, i.e. Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against omicron among all the variants with the IC50 of 4.9ng/ml (0.3 nM). We further solved the Cryo-EM structure of C5G2 in complex with the Spike trimer. The structure data showed that C5G2 bind to RBD mainly through its CDR3 at a vast region that not overlapping with the ACE2 binding surface. Surprisingly, C5G2 also bind to a distinct epitope residing in the NTD domain of spike protein through the same CDR3 loop, which may further increase its potency against the virus infection. Thus, this bi-paratopic nanobody may be served as an effective drug for the prophylaxis and therapy of the Omicron infection.

Application of "family member-like" care strategies among COVID-19 patients in an isolation ward. / "家属"ç §æŠ¤ç­–ç•¥åœ¨éš”ç¦»ç— æˆ¿çš„2019å† çŠ¶ç— æ¯’ç— æ‚£è€ ä¸­çš„åº”ç”¨.

OBJECTIVES: To control the pandemic of coronavirus disease 2019 (COVID-19) effectively, strict isolation measures have been taken in China. Suspected patients must be isolated, and the confirmed patients specifically are isolated in negative-pressure isolation rooms. During the isolation, patients face difficulty in adapting to their surrounding environment, worry about the prognosis of the disease, lack confidence in treatment, separate from their families, and have a sense of distance from medical staff. Isolated patients may possess the feelings of negativity, including loneliness, anxiety, depression, insomnia, and despair. Hence, to reduce the risk of adverse psychological outcomes, "family member-like" care strategies were developed and implemented to solve problems associated with the COVID-19 pandemic. This study aims to examine whether using "family member-like" care strategies can improve psychological resilience and reduce depression, anxiety, and stress symptoms among patients with COVID-19 in an isolation ward. METHODS: A quasi-experimental design was used to evaluate the "family member-like" care strategies for adult patients with COVID-19 in an isolation ward. COVID-19 patients in the Xiangya ward of the West District of the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology in Wuhan, Hubei province, were included in this study from February 9 to March 20, 2020. Healthcare providers who volunteered as family members were assigned to patients. They practiced one-to-one care and provided continuous and whole care for the patients who were from admission to discharge. Connor-Davidson Resilience Scale-10 (CD-RISC-10) and Depression Anxiety Stress Scale-21 (DASS-21) were used to evaluate the resilience and psychological status of COVID-19 inpatients upon hospital admission, 2 weeks after admission, and at their discharge from the hospital. RESULTS: The questionnaire response rate of the "family member-like" strategies was 100%. Of the 60 patients, 39 (65.0%) were male, and 21 (35%) were female. The hospital stay was (27.5±3.5) days. All the 60 patients were cured and discharged without any death and serious complications. The total scores for CD-RISC were 8.83±6.86 at admission, 29.13±5.42 at 2 weeks after admission, and 33.87±6.14 at discharge, which were significantly improved at the 2 follow-ups (F=404.564, P<0.001). Multivariate analysis and repeated measurements also indicated that patients experienced significant improvements in tenacity (F=360.839, P<0.001), strength (F=368.217, P<0.001), and optimism (F=328.456, P<0.001) at the 2 follow-ups. The total scores of DASS-21 were 49.27±11.30 at admission, 30.77±16.71 at 2 weeks after admission, and 4.17±11.03 at discharge, and the scores were significantly decreased at the 2 follow-ups (F=270.536, P<0.001). Multivariate analysis and repeated measurements also indicated that patients experienced significant decreases in depression (F=211.938, P<0.001), anxiety (F=285.592, P<0.001), and stress (F=287.478, P<0.001) at the 2 follow-ups. CONCLUSIONS: "Family member-like" strategies had positive effects on improving psychological resilience and reducing the symptoms of anxiety and depression of COVID-19 patients. It might be an effective care method for COVID-19 patients. It should be incorporated into emergency care management to improve care quality during public health emergencies of infectious diseases.

Critical Care for Patients with Severe Covid-2019 in Sichuan Province, China: Provincial Cohort Study (preprint)

Background Data regarding critical care for patients with severe COVID-19 are limited. We aimed to describe the clinical course, multi-strategy management, and respiratory support usage for the severe COVID-19 at the provincial level. Methods Using data from Sichuan Provincial Department of Health and the multicentre cohort study, all microbiologically confirmed COVID-19 patients in Sichuan who met the national severe criteria were included and followed-up from the day of inclusion (D1), until discharge, death, or the end of the study. Findings Out of 539 COVID-19 patients, 81 severe cases (15.0%) were identified. The median (IQR) age was 50 (39-65) years, 37% were female, and 53.1% had chronic comorbidities. All severe cases were identified before requiring mechanical ventilation and treated in the intensive care units (ICUs), among whom 51 (63.0%) were treated in provisional ICUs and 77 patients (95.1%) were admitted by D1. On D1, 76 (93.8%) were administered by respiratory support, including 55 (67.9%) by conventional oxygen therapy (COT), 8 (9.9%) by high-flow nasal cannula (HFNC) and 13 (16.0%) by non-invasive ventilation (NIV). By D28, 53 (65.4%) were discharged, three (3.7%) were deceased, and 25 (30.9%) were still hospitalized. COT, administered to 95.1% of the patients, was the most commonly used respiratory support and met 62.7% of the respiratory support needed, followed by HFNC (19.3%), NIV ventilation (9.4%) and IV 8.5%. Interpretation The multi-strategy management for severe COVID-19 patients including early identification and timely critical care may contribute to the low case-fatailty. Preparation of sufficient conventional oxygen equipment should be prioritized.