Simultaneous Detection of SARS-CoV-2 and Six Other Human Coronaviruses by Multiplex PCR and MALDI-TOF MS (preprint)

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is challenging the health systems worldwide, and large population testing is a vital step to control this pandemic. Here, we developed a new method (named HCoV-MS), which combines multiplex PCR with matrix-assisted laser desorption/ionization-time of flight mass spectrometry to simultaneously detect and differentiate seven human coronaviruses (HCoVs). The HCoV-MS method had good specificity and sensitivity, with a detection limit of 1-5 copies/reaction. To validate the HCoV-MS method, we tested 151 clinical samples, and the results showed good concordance with real-time PCR. In addition, 41 D614G variants were identified, which were consistent with the sequencing results. This method was also used in EQAE-SARS-COV in 2020, and all the samples were accurately identified. Taken together, HCoV-MS could be used as an effective method for large-scale detection. It was also capable of detecting key single nucleotide polymorphism about variants.

Lung ultrasound score as a predictor of failure to wean COVID-19 patients off mechanical ventilation: a prospective observational study (preprint)

Background The lung ultrasound score was developed for rapidly assessing the extent of lung ventilation, and it can predict failure to wean various types of patients off mechanical ventilation. Whether it is also effective for COVID-19 patients is unclear.Methods This single-center, prospective, observational study was conducted to assess the ability of the 12-region lung ultrasound score to predict failure to wean COVID-19 patients off ventilation. In parallel, we assessed whether right hemidiaphragmatic excursion or previously published predictors of weaning failure can apply to these patients. Predictive ability was assessed in terms of the area under the receiver operating characteristic curve (AUC).Results Among the 35 patients in the study, 12 patients (37%) could not be weaned off mechanical ventilation. The lung ultrasound score predicted these failures with an AUC of 0.885 (95% CI 0.770–0.999, p < 0.001), and a threshold score of 10 provided specificity of 72.7% and sensitivity of 92.3%. AUCs were lower for previously published predictors of weaning failure, and right hemidiaphragmatic excursion did not differ significantly between the two groups.Conclusions The lung ultrasound score can accurately predict failure to wean critically ill COVID-19 patients off mechanical ventilation, whereas assessment of right hemidiaphragmatic excursion does not appear helpful in this regard.Trial registration: https://clinicaltrials.gov/ct2/show/NCT05706441

Investigating the cumulative lag effects of environmental exposure under urban differences on COVID-19.

Although all walks of life are paying less attention to COVID-19, the spread of COVID-19 has never stopped. As an infectious disease, its transmission speed is closely related to the atmosphere environment, particularly the temperature (T) and PM2.5 concentrations. However, How T and PM2.5 concentrations are related to the spread of SARS-CoV-2 and how much their cumulative lag effect differ across cities is unclear. To identify the characteristics of cumulative lag effects of environmental exposure under city differences, this study used a generalized additive model to investigate the associations between T/PM2.5 concentrations and the daily number of new confirmed COVID-19 cases (NNCC) during the outbreak period in the second half of 2021 in Shaoxing, Shijiazhuang, and Dalian. The results showed that except for PM2.5 concentrations in Shaoxing, the NNCC in the three cities generally increased with the unit increase of T and PM2.5 concentrations. In addition, the cumulative lag effects of T/PM2.5 concentrations on NNCC in the three cities reached a peak at lag 26/25, lag 10/26, and lag 18/13 days, respectively, indicating that the response of NNCC to T and PM2.5 concentrations varies among different regions. Therefore, combining local meteorological and air quality conditions to adopt responsive measures is an important way to prevent and control the spread of SARS-CoV-2.

Different effects of vaccine on VST in critical and non-critical COVID-19 patients: A retrospective study of 363 cases.

Aim: To explore the risk factors of prolonged viral shedding time (VST) in critical/non-critical COVID-19 patients during hospitalization. Methods: In this retrospective study, we enrolled 363 patients with SARS-CoV-2 infection admitted in a designated hospital during the COVID-19 outbreak in Nanjing Lukou International Airport. Patients were divided into critical (n = 54) and non-critical (n = 309) groups. We analyzed the relationship between the VST and demographics, clinical characteristics, medications, and vaccination histories, respectively. Results: The median duration of VST was 24 d (IQR, 20-29) of all patients. The VST of critical cases was longer than non-critical cases (27 d, IQR, 22.0-30.0 vs. 23 d, IQR 20-28, P < 0.05). Cox proportional hazards model showed that ALT (HR = 1.610, 95%CI 1.186-2.184, P = 0.002) and EO% (HR = 1.276, 95%CI 1.042-1.563, P = 0.018) were independent factors of prolonged VST in total cases; HGB (HR = 0.343, 95%CI 0.162-0.728, P = 0.005) and ALP (HR = 0.358, 95%CI 0.133-0.968, P = 0.043) were independent factors of prolonged VST in critical cases, while EO% (HR = 1.251, 95%CI 1.015-1.541, P = 0.036) was the independent factor of prolonged VST in non-critical cases. Vaccinated critical cases showed higher levels of SARS-CoV-2-IgG (1.725 S/CO, IQR 0.3975-28.7925 vs 0.07 S/CO, IQR 0.05-0.16, P < 0.001) and longer VSTs (32.5 d, IQR 20.0-35.25 vs 23 d, IQR 18.0-30.0, P = 0.011) compared with unvaccinated critical patients. Fully vaccinated non-critical cases, however, presented higher levels of SARS-CoV-2-IgG (8.09 S/CO, IQR 1.6975-55.7825 vs 0.13 S/CO IQR 0.06-0.41, P < 0.001) and shorter VSTs (21 d, IQR 19.0-28.0 vs 24 d, IQR 21.0-28.5, P = 0.013) compared with unvaccinated non-critical patients. Conclusions: Our results suggested that risk factors of prolonged VST were different between critical and non-critical COVID-19 patients. Increased level of SARS-CoV-2-IgG and vaccination did not shorten the VST and hospital stay in critical COVID-19 patients.

The relationship between eHealth literacy and palliative care knowledge, attitudes, and practice among nurses: a cross-sectional study.

BACKGROUND: The crucial role that nurses play in offering palliative care to patients with life-threatening diseases is widely acknowledged, but the correlation between their eHealth literacy and their knowledge, attitudes, and practice in this domain has yet to be investigated. This study is conducted to investigate the status of eHealth literacy and knowledge, attitudes, and practice regarding palliative care among nurses, and to examine their relationship. METHODS: A cross-sectional study design was conducted among 546 nurses selected from the first-class tertiary hospitals located both inside and outside of Zhejiang Province between May 12 and May 20, 2022. The online survey of eHealth literacy scale (eHEALS) and scale of knowledge, attitudes, and practice (KAP) regarding palliative care was performed using snowball sampling through the WeChat mini program "Questionnaire Star". The Spearman rank correlation and binary logistic regression model were used to analyze the independent association between eHealth literacy and KAP toward palliative care. RESULTS: The median scores of eHEALS and KAP regarding palliative care were 32 (interquartile range[IQR] 29 to 38) and 82 (IQR 54 to 106) points. The results of correlation analysis showed that the KAP regarding palliative care was significantly correlated with eHEALS (rho = 0.189, P < 0.001). In addition, the results of binary logistic regression analysis demonstrated that the eHEALS score was independently associated with the KAP score regarding palliative care when controlling for sociodemographic factors (OR = 2.109; P < 0.001). CONCLUSION: Nurses who worked in first-class tertiary hospitals have good levels of eHealth literacy, while the overall level of KAP regarding palliative care is moderate. Our findings highlight that the eHEALS score is independently associated with the KAP score regarding palliative care. Therefore, nursing managers should adopt multiple measures to comprehensively improve eHealth literacy among nurses, further enrich their knowledge of palliative care, promote a positive transformation of attitudes towards palliative care, and efficiently implement palliative care practice, in order to promote high-quality development of palliative care.

Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome.

Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn't alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic. Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging. It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues; factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal; results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed. With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white; changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected. In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response; metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered. The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.

Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome : 针刺调控慢性疲劳综合征中枢机制研究进展

Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn't alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic. Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging. It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues;factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal;results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed. With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white;changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected. In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response;metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered. The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.

Post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis.

Background: Post-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors. Methods: This study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I 2 index were used to evaluate heterogeneity in this meta-analysis. Results: Six observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90-5.32), anxiety (OR = 3.09, 95% CI = 1.47-6.47), myalgia (OR = 2.33, 95% CI = 1.02-5.33), and hair loss (OR = 2.76, 95% CI = 1.07-7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients. Conclusion: The findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.

AZD7442 (Tixagevimab/Cilgavimab) for Post-exposure Prophylaxis of Symptomatic COVID-19.

BACKGROUND: We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19). METHODS: Adults without prior SARS-CoV-2 infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2-infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab consecutively) or placebo. Primary endpoints were safety and first post-dose SARS-CoV-2 reverse-transcription-polymerase-chain-reaction (RT-PCR)-positive symptomatic COVID-19 event before day 183. RESULTS: 1121 participants were randomized and dosed (mean age 46 years; 49% females; AZD7442, n=749; placebo, n=372). Median (range) follow-up was 49 (5-115) and 48 (20-113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction 33.3%; 95% confidence interval [CI] -25.9 to 64.7; P=.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR-negative (n=974 [87%]) or missing an RT-PCR result (n=99 [9%]) at baseline, AZD7442 reduced RT-PCR-positive symptomatic COVID-19 by 73.2% (95% CI 27.1 to 90.1) versus placebo. CONCLUSIONS: This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined analysis of participants who were SARS-CoV-2 RT-PCR-negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19.

Correlation analysis of self-directed learning ability, self-efficacy and academic burnout of junior nursing college students in closed management colleges.

AIMS: To understand the status quo of self-directed learning ability, self-efficacy and academic burnout of junior nursing college students, since the closed management mode was implemented during COVID-19 pandemic disease. DESIGN: Cross-sectional study. METHODS: Participants came from 3,051 junior nursing college students of a college in Zhengzhou City, Henan Province, China. Data were collected by online questionnaire and analysed by SPSS25.0 (a statistical package for social science) and AMOS24.0 software. RESULTS: High self-directed learning ability and self-efficacy were related to low levels of academic burnout (p < .01). In addition, the analysis of mediation effect indicated that the influence of self-directed learning ability on academic burnout was not mediated by self-efficacy.

Qualitative descriptive study during the COVID-19 pandemic on the needs of informal caregivers of Chinese minors who underwent craniopharyngioma surgery.

PURPOSE: To determine the needs of informal caregivers during the long-term health management of minors who have undergone craniopharyngioma surgery. Design and methodology This is a qualitative and descriptive research study. Purposive sampling was used to select participants, and semi-structured interviews were conducted to explore the needs of 21 informal caregivers for postoperative minors. Due to the COVID-19 pandemic, the respondents were provided with the options of online video call or offline one-on-one interviews. Following this, a content analysis method was conducted. RESULTS: Four themes and 14 sub-themes were extracted from the results of the study, including needs for relieving psychological stress (including psychological pressure on both minors and on caregivers); requirement for on-campus assistance (physical activity, eliminating verbal violence in schools, special education needs for child, healthcare services provided by school hospitals); demands for medical help (acquiring medical knowledge, need for medication management, convenience and reliable access to medical services, need for technological development, expectations of multidisciplinary cooperation, the necessity of health review reminders); and the desire for financial aid (charity platform assistance, inclination of government policy). CONCLUSIONS: In China, informal caregivers of young patients with onset craniopharyngioma require both the multidisciplinary cooperation of medical institutions and the multi-departmental cooperation of society. Information and medical technology advancements may benefit families with young patients. Improving community hospitals' medical services and encouraging the practical use of online medical treatment and prescriptions are both necessary in the context of COVID-19. PRACTICE IMPLICATIONS: By identifying the needs of informal caregivers, medical professionals are able to develop care plans and interventions aimed at reducing the burden of care for minors who have undergone craniopharyngioma surgery.

Advances of mRNA vaccine in tumor: a maze of opportunities and challenges.

High-frequency mutations in tumor genomes could be exploited as an asset for developing tumor vaccines. In recent years, with the tremendous breakthrough in genomics, intelligence algorithm, and in-depth insight of tumor immunology, it has become possible to rapidly target genomic alterations in tumor cell and rationally select vaccine targets. Among a variety of candidate vaccine platforms, the early application of mRNA was limited by instability low efficiency and excessive immunogenicity until the successful development of mRNA vaccines against SARS-COV-2 broken of technical bottleneck in vaccine preparation, allowing tumor mRNA vaccines to be prepared rapidly in an economical way with good performance of stability and efficiency. In this review, we systematically summarized the classification and characteristics of tumor antigens, the general process and methods for screening neoantigens, the strategies of vaccine preparations and advances in clinical trials, as well as presented the main challenges in the current mRNA tumor vaccine development.

Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: A retrospective study of 25207 cases in a Fangcang hospital.

Objectives: To summarize the clinical characteristics of patients infected by SARS-CoV-2 omicron variant and explore the risk factors affecting the progression in a Fangcang hospital, Shanghai, China. Methods: A total of 25,207 patients were retrospectively enrolled. We described the clinical characteristics and performed univariate and multivariate logistic regression analysis to identify the risk factors for non-severe to severe COVID-19 or death. Results: According to the outcomes, there were 39 severe patients (including 1 death) and 25,168 non-severe patients enrolled in this study. Among the 25,207 cases, the median age was 45 years (IQR 33-54), and 65% patients were male. Cough (44.5%) and expectoration (38.4%) were the most two common symptoms. Hypertension (10.4%) and diabetes (3.5%) were most two common comorbidities. Most patients (81.1%) were fully vaccinated. The unvaccinated and partially vaccinated patients were 15.1% and 3.9%, respectively. The length of viral shedding time was six days (IQR 4-9) in non-severe patients. Multivariate logistic regression analysis suggested that age (OR=1.062, 95%CI 1.034-1.090, p<0.001), fever (OR=2.603, 95%CI 1.061-6.384, p=0.037), cough (OR=0.276, 95%CI 0.119-0.637, p=0.003), fatigue (OR=4.677, 95%CI 1.976-11.068, p<0.001), taste disorders (OR=14.917, 95%CI 1.884-118.095, p=0.010), and comorbidity (OR=2.134, 95%CI 1.059-4.302, p=0.034) were predictive factors for deterioration of SARS-CoV-2 omicron variant infection. Conclusions: Non-critical patients have different clinical characteristics from critical patients. Age, fever, cough, fatigue, taste disorders, and comorbidity are predictors for the deterioration of SARS-CoV-2 omicron variant infection.

Targeting autophagy regulation in NLRP3 inflammasome-mediated lung inflammation in COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late stage of COVID-19. Here, we discuss the autophagy regulation at different stages of COVID-19. Specifically, we highlight the therapeutic potential of autophagy activators in COVID-19 by inhibiting the NLRP3 inflammasome, thereby avoiding the cytokine storm. We hope this review provides enlightenment for the use of autophagy activators targeting the inhibition of the NLRP3 inflammasome, specifically the combinational therapy of autophagy modulators with the inhibitors of the NLRP3 inflammasome, antiviral drugs, or anti-inflammatory drugs in the fight against COVID-19.

Bioinformatics-based SARS-CoV-2 epitopes design and the impact of Spike protein mutants on epitope humoral immunities

Graphical Background Epitope selection is the key to peptide vaccines development. Bioinformatics tools can efficiently improve the screening of antigenic epitopes and help to choose the right ones. Objective To predict, synthesize and testify peptide epitopes at spike protein, assess the effect of mutations on epitope humoral immunity, thus provide clues for the design and development of epitope peptide vaccines against SARS-CoV-2. Methods Bioinformatics servers and immunological tools were used to identify the helper T lymphocyte, cytotoxic T lymphocyte, and linear B lymphocyte epitopes on the S protein of SARS-CoV-2. Physicochemical properties of candidate epitopes were analyzed using IEDB, VaxiJen, and AllerTOP online software. Three candidate epitopes were synthesized and their antigenic responses were evaluated by binding antibody detection. Results A total of 20 antigenic, non-toxic and non-allergenic candidate epitopes were identified from 1502 epitopes, including 6 helper T-cell epitopes, 13 cytotoxic T-cell epitopes, and 1 linear B cell epitope. After immunization with antigen containing candidate epitopes S206-221, S403-425, and S1157-1170 in rabbits, the binding titers of serum antibody to the corresponding peptide, S protein, receptor-binding domain protein were (415044, 2582, 209.3), (852819, 45238, 457767) and (357897, 10528, 13.79), respectively. The binding titers to Omicron S protein were 642, 12878 and 7750, respectively, showing that N211L, DEL212 and K417N mutations cause the reduction of the antibody binding activity. Conclusions Bioinformatic methods are effective in peptide epitopes design. Certain mutations of the Omicron would lead to the loss of antibody affinity to Omicron S protein.

The Association between Post-Traumatic Stress Disorder and Psychological Distress among Primary School and Middle School Teachers during the COVID-19 Epidemic: A Moderated Mediation Analysis

Background: The outbreak of the coronavirus disease (COVID-19) and its rapid spread may have led to individuals developing post-traumatic stress disorder (PTSD) and psychological distress. Under this context, teachers merit more attention as a group with high levels of work stress. The purpose of this study was to verify the relationship between PTSD and psychological distress and to explore sleep problems as a possible mediator in the relationship between PTSD and psychological distress, as well as the moderator of internet gaming disorders (IGD) in the relationship between sleep problems and psychological distress. Methods: A total of 11,014 Chinese primary and middle school teachers participated in this study. The survey was conducted online between 25 May and 30 June 2020. Results: PTSD was shown to have both a direct and indirect effect on teachers' psychological distress. The indirect effect was mediated by sleep problems. IGD played a moderating role between sleep problems and psychological distress. Conclusions: During the COVID-19 pandemic, PTSD has been shown to have had a serious impact on the psychological stress of teachers, which was mediated by sleep problems. In addition, IGD raised the harm brought from sleep problems on teachers' mental health.