Effect of the Timing of Amubarvimab/Romlusevimab (BRII-196/198) Administration on Progression to Severe Disease in Elderly Patients with COVID-19 Infection: A Retrospective Cohort Study

Objective Early intervention with neutralizing antibodies is considered to be effective in preventing disease progression in patients with mild to moderate COVID-19 infection. Elderly patients are the most susceptible and at a higher risk of COVID-19 infection. The present study aimed to assess the necessity and possible clinical benefits of the early administration of Amubarvimab/Romlusevimab (BRII-196/198) in the elderly population. Methods The present study was designed as a retrospective, multi-center cohort study conducted with 90 COVID-19 patients aged over 60, who were divided into two groups based on the timing of the administration of BRII-196/198 (administration at ≤ 3 days or > 3 days from the onset of infection symptoms). Results The ≤ 3 days group exhibited a greater positive effect (HR 5.94, 95% CI, 1.42–24.83;P < 0.01), with only 2 patients among 21 patients (9.52%) exhibiting disease progression, compared to the 31 patients among the 69 patients (44.93%) of the > 3 days group who exhibited disease progression. The multivariate Cox regression analysis revealed low flow oxygen support prior to BRII-196/198 administration (HR 3.53, 95% CI 1.42–8.77, P < 0.01) and PLT class (HR 3.68, 95% CI 1.37–9.91, P < 0.01) as independent predictors of disease progression. Conclusions In elderly patients with mild or moderate COVID-19 disease, who do not require oxygen support and had the risk factors for disease progression to severe COVID-19 disease, the administration of BRII-196/198 within 3 days resulted in a beneficial trend in terms of preventing disease progression.

Development and application of a multiplex fluorescent quantitative RT-PCR for detection of Porcine epidemic diarrhea virus, porcine coronavirus and porcine acute diarrhea syndrome coronavirus

To develop a multiplex fluorescent quantitative RT-PCR for the detection of porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV), in this study, specific primers/probes were designed based on the conserved regions of M, M and N gene sequences of PEDV, PDCoV and SADS-CoV, respectively. After optimization of the reaction conditions, a multiplex fluorescent quantitative RT-PCR for PEDV, PDCoV and SADS-CoV was established. The results of specificity assay showed that the method was positive for detection of PEDV, PDCoV and SADS-CoV, and negative for detection of porcine transmissible gastroenteritis virus, porcine rotavirus, porcine reproductive and respiratory syndrome virus, porcine pseudorabies virus, porcine circovirus type 2, porcine parvovirus, classical swine fever virus and foot-and-mouth disease virus. The results of sensitivity assay showed that the detection limit of this method for PEDV, PDCoV, and SADS-CoV plasmids standard was 1.0x101 copies/L, and had a good linear relationship with their Ct values in the range of 101 copies/L to 106 copies/L. The results of repeatability assay showed that the coefficients of variation (CVs) of intra- and inter-assay reproducibility ranged from 0.33% to 2.53%, indicating good repeatability and stability. To evaluate the effects of the developed method, 100 clinical samples collected from different parts of Henan province were used for detection of these three viruses and compared with those of single RT-PCR and standard methods. The results of multiplex fluorescent quantitative RT-PCR showed that the positive rates of PEDV, PDCoV and SADS-CoV were 38% (38/100), 14% (14/100) and 5% (5/100), respectively. There was no mixed infection. The coincidence rate with the standard detection methods of PEDV and PDCoV was 100%, and the sensitivity was higher than that of single RT-PCR. In this study, a specific, sensitive and rapid multiplex fluorescent quantitative RTPCR method was established for the first time, which could be used for the differential detection of PEDV, PDCoV and SADS-CoV, and laid a foundation for the differential diagnosis and control of porcine diarrheal diseases.

Persistent lymphocyte reduction and interleukin-6 levels are independently associated with death in patients with COVID-19.

To investigate the value of the peripheral blood lymphocyte count (LYM) combined with interleukin-6 (IL-6) in predicting disease severity and prognosis in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. This was a prospective observational cohort study. A total of 109 patients with SARS-CoV-2 pneumonia who were admitted to Nanjing First Hospital from December 2022 to January 2023 were enrolled. The patients were divided into two groups based on disease severity: severe (46 patients) and critically ill (63 patients). The clinical data of all patients were collected. The clinical characteristics, sequential organ failure assessment (SOFA) score, peripheral blood lymphocyte count, IL-6 level and other laboratory test results were compared between the two groups. A receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of each index for SARS-CoV-2 pneumonia severity; patients were regrouped using the optimal cut-off value of the ROC curve, and the relationship between different LYM and IL-6 levels and the prognosis of patients was analysed. Kaplan‒Meier survival curve analysis was performed; in the different LYM and IL-6 groups, the patients were regrouped based on whether thymosin was used, and the effect of thymosin on patient prognosis was compared between the groups. Patients in the critically ill group were significantly older than patients in the severe group (age: 78 ± 8 vs. 71 ± 17, t = 2.982, P < 0.05), and the proportion of patients with hypertension, diabetes and cerebrovascular disease was significantly higher in the critically ill group than in the severe group (69.8% vs. 45.7%, 38.1% vs. 17.4%, 36.5% vs. 13.0%; χ2 values, 6.462, 5.495, 7.496, respectively, all P < 0.05). Compared with the severe group, the critically ill group had a higher SOFA score on admission (score: 5.4 ± 3.0 vs. 1.9 ± 1.5, t = 24.269, P < 0.05); IL-6 and procalcitonin (PCT) in the critically ill group were significantly higher than those in the severe group on the first day of admission [288.4 (191.4, 412.9) vs. 513.0 (288.2, 857.4), 0.4 (0.1, 3.2) vs. 0.1 (0.05, 0.2); Z values, 4.000, 4.456, both P < 0.05]. The lymphocyte count continued to decline, and the lymphocyte count on the 5th day (LYM-5d) was still low (0.6 ± 0.4 vs. 1.0 ± 0.4, t = 4.515, both P < 0.05), with statistically significant differences between the two groups. ROC curve analysis indicated that LYM-5d, IL-6 and LYM-5d + IL-6 all had value for predicting SARS-CoV-2 pneumonia severity; the areas under the curve (AUCs) were 0.766, 0.725, and 0.817, respectively, and the 95% confidence intervals (95% CI) were 0.676-0.856, 0.631-0.819, and 0.737-0.897, respectively. The optimal cut-off values for LYM-5d and IL-6 were 0.7 × 109/L and 416.4 pg/ml, respectively. LYM-5d + IL-6 had the greatest value in predicting disease severity, and LYM-5d had higher sensitivity and specificity in predicting SARS-CoV-2 pneumonia severity. Regrouping was performed based on the optimal cut-off values for LYM-5d and IL-6. Comparing the IL-6 ≥ 416.4 pg/ml and LYM-5d < 0.7 × 109/L group with the other group, i.e., patients in the non-low-LYM-5d and high-IL-6 group, patients in the low-LYM-5d and high-IL-6 group had a higher 28-day mortality rate (71.9% vs. 29.9%, χ2 value 16.352, P < 0.05) and a longer hospital stay, intensive care unit (ICU) stay and mechanical ventilation time (days: 13.7 ± 6.3 vs. 8.4 ± 4.3, 9.0 (7.0, 11.5) vs. 7.5 (4.0, 9.5), 8.0 (6.0, 10.0) vs. 6.0 (3.3, 8.5); t/Z values, 11.657, 2.113, 2.553, respectively, all P < 0.05), as well as a higher incidence of secondary bacterial infection during the disease course (75.0% vs. 41.6%, χ2 value 10.120, P < 0.05). Kaplan‒Meier survival analysis indicated that the median survival time of patients in the low LYM-5d and high-IL-6 group was significantly shorter than that of patients in the non-low LYM-5d and high-IL-6 group (14.5 ± 1.8 d vs. 22.2 ± 1.1 d, Z value 18.086, P < 0.05). There was no significant difference in the curative effect between the thymosin group and the nonthymosin group. LYM and IL-6 levels are closely related to SARS-CoV-2 pneumonia severity. The prognosis for patients with IL-6 ≥ 416.4 pg/ml at admission and a lymphocyte count < 0.7 × 10 9/L on the 5th day is poor.

Sequential Administration of SARS-CoV-2 Strains-Based Vaccines Effectively Induces Potent Immune Responses against Previously Unexposed Omicron Strain.

In the past few years, the continuous pandemic of COVID-19 caused by SARS-CoV-2 has placed a huge burden on public health. In order to effectively deal with the emergence of new SARS-CoV-2 variants, it becomes meaningful to further enhance the immune responses of individuals who have completed the first-generation vaccination. To understand whether sequential administration using different variant sequence-based inactivated vaccines could induce better immunity against the forthcoming variants, we tried five inactivated vaccine combinations in a mouse model and compared their immune responses. Our results showed that the sequential strategies have a significant advantage over homologous immunization by inducing robust antigen-specific T cell immune responses in the early stages of immunization. Furthermore, the three-dose vaccination strategies in our research elicited better neutralizing antibody responses against the BA.2 Omicron strain. These data provide scientific clues for finding the optimal strategy within the existing vaccine platform in generating cross-immunity against multiple variants including previously unexposed strains.

A comprehensive analysis of systematically screened laboratory tests: based on a COVID-19 cohort.

INTRODUCTION: The study aimed at screening indicators with differential diagnosis values and investigating the characteristics of laboratory tests in COVID-19 patients. METHODOLOGY: All the laboratory tests from COVID-19 patients and non-COVID-19 patients in this cohort were included. Test values from the groups during the course, days 1-7, and days 8-14 were analyzed. Mann-Whitney U test, univariate logistic regression analysis, and multivariate regression analysis were performed. Regression models were established to verify the diagnostic performance of indicators. RESULTS: 302 laboratory tests were included in this cohort, and 115 indicators were analyzed; the values of 61 indicators had significant differences (p < 0.05) between groups, and 23 indicators were independent risk factors of COVID-19. During days 1-7, the values of 40 indicators had significant differences (p < 0.05) between groups, while 20 indicators were independent risk factors of COVID-19. During days 8-14, the values of 45 indicators had significant differences (p < 0.05) between groups, and 23 indicators were independent risk factors of COVID-19. About 10, 12, and 12 indicators showed significant differences (p < 0.05) in multivariate regression analysis in different courses respectively, and the diagnostic performance of the model from them was 74.9%, 80.3%, and 80.8% separately. CONCLUSIONS: The indicators obtained through systematic screening have preferable differential diagnosis values. Compared with non-COVID-19 patients, the screened indicators indicated that COVID-19 patients had more severe inflammatory responses, organ damage, electrolyte and metabolism disturbance, and coagulation disorders. This screening approach could find valuable indicators from a large number of laboratory test indicators.

Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents.

Introduction: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies. Methods: In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies. Results and discussion: We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.

Nirmatrelvir/ritonavir use in patients with COVID-19 on hemodialysis: a case series

Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to four patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.

Machine learning approach combined with causal relationship inferring unlocks the shared pathomechanism between COVID-19 and acute myocardial infarction.

Background: Increasing evidence suggests that people with Coronavirus Disease 2019 (COVID-19) have a much higher prevalence of Acute Myocardial Infarction (AMI) than the general population. However, the underlying mechanism is not yet comprehended. Therefore, our study aims to explore the potential secret behind this complication. Materials and methods: The gene expression profiles of COVID-19 and AMI were acquired from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed genes (DEGs) shared by COVID-19 and AMI, we conducted a series of bioinformatics analytics to enhance our understanding of this issue. Results: Overall, 61 common DEGs were filtered out, based on which we established a powerful diagnostic predictor through 20 mainstream machine-learning algorithms, by utilizing which we could estimate if there is any risk in a specific COVID-19 patient to develop AMI. Moreover, we explored their shared implications of immunology. Most remarkably, through the Bayesian network, we inferred the causal relationships of the essential biological processes through which the underlying mechanism of co-pathogenesis between COVID-19 and AMI was identified. Conclusion: For the first time, the approach of causal relationship inferring was applied to analyzing shared pathomechanism between two relevant diseases, COVID-19 and AMI. Our findings showcase a novel mechanistic insight into COVID-19 and AMI, which may benefit future preventive, personalized, and precision medicine.Graphical abstract.

Role of Parents' Perceived Risk and Responsibility in Deciding on Children's COVID-19 Vaccination.

OBJECTIVES: We examined associations between parents' reports for whether their children had been vaccinated against coronavirus disease 2019 (COVID-19) and parents' perceptions of the vaccine's long-term risk, as well as their own sense of responsibility on deciding to vaccinate or not vaccinate their children. METHODS: During the period when the Omicron variant was dominant (February-March 2022), we surveyed parents from a nationally representative, probability-based Internet panel about vaccination of their school-aged children, perceptions that the vaccine's long-term risk exceeds risks without vaccination (henceforth: comparative long-term risk), their tendency to feel more responsible if their child became sick from vaccination than when unvaccinated (henceforth: anticipated responsibility), and their own vaccination status. We used multivariate analyses to assess associations of children's COVID-19 vaccination with parental comparative long-term risk perceptions, anticipated responsibility, parents' vaccination status, and demographics. RESULTS: Among 1715 parent respondents (71% of eligible), 45% perceived vaccine-related comparative long-term risk and 18% perceived greater anticipated responsibility from vaccination than no vaccination. After accounting for parental vaccination, parents who were more concerned about comparative long-term risk and who reported greater anticipated responsibility were 6% (95% confidence interval, -0.09 to -0.03; P < .001) and 15% (95% confidence interval, -0.19 to -0.11; P < .001) less likely to have vaccinated their children, respectively. Findings were driven by vaccinated parents. CONCLUSIONS: Parents' perceptions of the COVID-19 vaccine's long-term comparative risk and their greater anticipated responsibility for children getting sick if vaccinated (versus not) were associated with lower vaccine uptake among children of vaccinated parents.

An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters.

Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.

A Phase 1, Randomized, Double-Blinded, Placebo-Controlled and Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Intranasal DelNS1-nCoV-RBD LAIV for COVID-19 in Healthy Adults.

An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18-55 and COVID-19 vaccines naïve, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 × 107 EID50/ dose and 1 × 107.7 EID50/ dose in 0.2 mL respectively. The placebo vaccine was composed of inert excipients/dose in 0.2 mL. Recruited participants were administered the vaccine intranasally on day 0 and day 28. The primary end-point was the safety of the vaccine. The secondary endpoints included cellular, humoral, and mucosal immune responses post-vaccination at pre-specified time-points. The cellular response was measured by the T-cell ELISpot assay. The humoral response was measured by the serum anti-RBD IgG and live-virus neutralizing antibody against SARS-CoV-2. The saliva total Ig antibody responses in mucosal secretion against SARS-CoV-2 RBD was also assessed. Twenty-nine healthy Chinese participants were vaccinated (low-dose: 11; high-dose: 12 and placebo: 6). The median age was 26 years. Twenty participants (69%) were male. No participant was discontinued due to an adverse event or COVID-19 infection during the clinical trial. There was no significant difference in the incidence of adverse events (p = 0.620). For the T-cell response elicited after full vaccination, the positive PBMC in the high-dose group increased to 12.5 SFU/106 PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/106 PBMC (day 42) from 2.5 SFU/106 PBMC (baseline) in the placebo group. The high-dose group showed a slightly higher level of mucosal Ig than the control group after receiving two doses of the vaccine (day 31, 0.24 vs. 0.21, p = 0.046; day 56 0.31 vs. 0.15, p = 0.45). There was no difference in the T-cell and saliva Ig response between the low-dose and placebo groups. The serum anti-RBD IgG and live virus neutralizing antibody against SARS-CoV-2 were undetectable in all samples. The high-dose intranasal DelNS1-nCoV-RBD LAIV is safe with moderate mucosal immunogenicity. A phase-2 booster trial with a two-dose regimen of the high-dose intranasal DelNS1-nCoV-RBD LAIV is warranted.

Longitudinal associations of serum survivin with the severity and prognosis of community-acquired pneumonia patients.

BACKGROUND: Survivin is a member of apoptosis inhibitor proteins that evokes cellular proliferation and inhibits apoptosis. However, the role of survivin in community-acquired pneumonia (CAP) patients remains to be firmly established. The aim of this cohort study was to evaluate the correlations of serum survivin with the severity and prognosis of CAP patients. METHODS: This research included 470 eligible CAP patients. Serum fasting samples were drawn from patients, and serum survivin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, demographic characteristics and clinical information were collected. The prognosis of CAP patients was tracked. RESULTS: Serum survivin gradually decreased with elevated CAP severity scores. Additionally, the correlative analysis suggested that serum survivin was associated with many clinical characteristics. Furthermore, mixed linear and logistic regression models indicated that serum survivin was negatively associated with severity. After adjusting for confounding factors, logistic regression analyses found that lower serum survivin on admission elevated the risks of mechanical ventilation, vasoactive agent usage, longer hospital stays, ICU admission, and even death during hospitalization. Serum survivin in combination with CAP severity scores elevated the predictive capacities for severity and death in CAP patients compared with a single indicator. CONCLUSION: On admission, there are inverse dose-response associations of serum survivin with severity and poor prognosis in CAP patients, demonstrating that serum survivin may be involved in the pathophysiology process of CAP. Serum survivin may serve as a potential biomarker for disease evaluation and prognosis in CAP patients.

Knowledge, attitude, and practices on COVID-19 prevention and diagnosis among medical workers in the radiology department: A multicenter cross-sectional study in China

Objective The aim of this study was to investigate the knowledge, attitude, and practice (KAP) of medical workers in the radiology department toward the prevention and diagnosis of COVID-19. Methods This multicenter cross-sectional study was conducted among medical workers in the radiology department of 17 hospitals between March and June 2022. Results A total of 324 medical workers were enrolled. The mean knowledge scores were 15.3 ± 3.4 (out of 23), attitude scores were 31.1 ± 5.6 (range 8–40), and practice scores were 35.1 ± 4.4 (range 8–40). Positive attitudes (OR = 1.235, 95% CI: 1.162–1.311, P < 0.001) and aged 41–50 years were independently associated with higher practice scores. Those with the better practice were more likely to be older (OR = 2.603, 95% CI: 1.242–5.452, P = 0.011), nurses (OR = 2.274, 95% CI: 1.210–4.272, P = 0.011) and with junior/intermediary/vice-senior title (OR = 2.326, 95% CI: 1.030–5.255, P = 0.042;OR = 2.847, 95% CI: 1.226–6.606, P = 0.015;OR = 4.547, 95% CI: 1.806–11.452, P = 0.001, respectively). Subgroup analysis revealed significant differences in knowledge between technicians and physicians and nurses and between staff working in tertiary hospitals and non-tertiary hospitals. Knowledge is positively correlated with attitude (β = 0.54, P < 0.001), and attitude is positively correlated with practice (β = 0.37, P < 0.001). Attitudes significantly mediated the association between knowledge and practice (β = 0.119, P < 0.001). Conclusion The radiology medical workers showed moderate knowledge but good attitudes and practices of prevention and diagnosis of COVID-19. Attitudes were found to be positively associated with better practices of prevention and diagnosis of COVID-19. Attitudes significantly mediated the association between knowledge and practice.

A DNA Vaccine Encoding the Full-Length Spike Protein of Beta Variant (B.1.351) Elicited Broader Cross-Reactive Immune Responses against Other SARS-CoV-2 Variants.

The SARS-CoV-2 pandemic remains an ongoing threat to global health with emerging variants, especially the Omicron variant and its sub-lineages. Although large-scale vaccination worldwide has delivered outstanding achievements for COVID-19 prevention, a declining effectiveness to a different extent in emerging SARS-CoV-2 variants was observed in the vaccinated population. Vaccines eliciting broader spectrum neutralizing antibodies and cellular immune responses are urgently needed and important. To achieve this goal, rational vaccine design, including antigen modeling, screening and combination, vaccine pipelines, and delivery, are keys to developing a next-generation COVID-19 vaccine. In this study, we designed several DNA constructs based on codon-optimized spike coding regions of several SARS-CoV-2 variants and analyzed their cross-reactive antibodies, including neutralizing antibodies, and cellular immune responses against several VOCs in C57BL/6 mice. The results revealed that different SARS-CoV-2 VOCs induced different cross-reactivity; pBeta, a DNA vaccine encoding the spike protein of the Beta variant, elicited broader cross-reactive neutralizing antibodies against other variants including the Omicron variants BA.1 and BA.4/5. This result demonstrates that the spike antigen from the Beta variant potentially serves as one of the antigens for multivalent vaccine design and development against variants of SARS-CoV-2.

Comment on "Crosstalk between gut microbiota and COVID-19 impacts pancreatic cancer progression".

The coronavirus disease 2019 (COVID-19) pandemic has become a global burden, further exacerbating the occurrence of risk events in cancer patients. The high risk of death from pancreatic cancer makes it one of the most lethal malignancies. Recently, it was reported in the World Journal of Gastrointestinal Oncology that COVID-19 influences pancreatic cancer progression via the lung-gut-pancreatic axis, and the authors provided insights into the intrinsic crosstalk mechanisms in which the gut microbiota is involved, the characteristics and effects of inflammatory factors, and immunotherapeutic strategies for treating both diseases. Here, we review the latest cutting-edge researches in the field of the lung-gut-pancreatic axis and discuss future perspectives to address the severe survival challenges posed by the COVID-19 pandemic in patients with pancreatic cancer.

Impact of the COVID-19 pandemic on emergent stroke care in Beijing, China.

The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented disruption to health care systems around the globe. Stroke is still an ongoing issue during the pandemic. We investigated the impact of the COVID-19 outbreak on emergent stroke care in Beijing, China. This is a retrospective analysis of two groups of patients with acute ischaemic stroke (AIS) registered in the Beijing Emergency Care Database between January 1, 2019, and December 31, 2020. Based on a database including 77 stroke centres, the quantity and quality of emergency care for stroke were compared. Subgroup analyses based on hospitals in different areas (high-risk and low/medium-risk areas) were carried out. A total of 6440 and 8699 admissions with suspected stroke were recorded in 2020 and 2019, respectively. There were no significant differences in the mean age and sex distribution for the patients between the two observational periods. The number of AIS admissions decreased by approximately 23.9% during the COVID-19 pandemic compared to that during the prepandemic period. The proportions of intravenous thrombolysis and endovascular treatment were 76.4% and 13.1%, respectively, in 2020, which were higher than those in 2019 (71.7% and 9.3%, respectively). There was no statistically significant difference in the time from stroke onset to arrival at the hospital (97.97 ± 23.09 min vs. 99.40 ± 20.76 min, p = 0.832) between the two periods. The door-to-needle time for thrombolysis (44.92 ± 9.20 min vs. 42.37 ± 9.06 min, p < 0.001) and door-to-thrombectomy time (138.56 ± 32.45 min vs. 120.55 ± 32.68 min, p < 0.001) were increased significantly in the pandemic period compared to those in the prepandemic period, especially in hospitals in high-risk areas. The decline in the number of patients with AIS and delay in treatment started after the launch of the level-1 public health emergency response and returned to stability after the release of professional protocols and consensus statements. Disruptions to medical services during the COVID-19 pandemic have substantially impacted AIS patients, with a clear drop in admission and a decline in the quality of emergent AIS care, especially in hospitals in high-risk areas and at the time of the initial outbreak of COVID-19. Health care systems need to maintain rapid adaptation to possible outbreaks of COVID-19 or similar crises in the future.

A novel, ultrafast, ultrasensitive diagnosis platform for the detection of SARS-COV-2 using restriction endonuclease-mediated reverse transcription multiple cross displacement amplification.

Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Though many methods have been used for detecting SARS-COV-2, development of an ultrafast and highly sensitive detection strategy to screen and/or diagnose suspected cases in the population, especially early-stage patients with low viral load, is significant for the prevention and treatment of COVID-19. In this study, a novel restriction endonuclease-mediated reverse transcription multiple cross displacement amplification (MCDA) combined with real-time fluorescence analysis (rRT-MCDA) was successfully established and performed to diagnose COVID-19 infection (COVID-19 rRT-MCDA). Two sets of specific SARS-COV-2 rRT-MCDA primers targeting opening reading frame 1a/b (ORF1ab) and nucleoprotein (NP) genes were designed and modified according to the reaction mechanism. The SARS-COV-2 rRT-MCDA test was optimized and evaluated using various pathogens and clinical samples. The optimal reaction condition of SARS-COV-2 rRT-MCDA assay was 65°C for 36 min. The SARS-COV-2 rRT-MCDA limit of detection (LoD) was 6.8 copies per reaction. Meanwhile, the specificity of SARS-COV-2 rRT-MCDA assay was 100%, and there was no cross-reaction with nucleic acids of other pathogens. In addition, the whole detection process of SARS-COV-2 rRT-MCDA, containing the RNA template processing (15 min) and real-time amplification (36 min), can be accomplished within 1 h. The SARS-COV-2 rRT-MCDA test established in the current report is a novel, ultrafast, ultrasensitive, and highly specific detection method, which can be performed as a valuable screening and/or diagnostic tool for COVID-19 in clinical application.

Knowledge, attitude, and practices on COVID-19 prevention and diagnosis among medical workers in the radiology department: A multicenter cross-sectional study in China.

Objective: The aim of this study was to investigate the knowledge, attitude, and practice (KAP) of medical workers in the radiology department toward the prevention and diagnosis of COVID-19. Methods: This multicenter cross-sectional study was conducted among medical workers in the radiology department of 17 hospitals between March and June 2022. Results: A total of 324 medical workers were enrolled. The mean knowledge scores were 15.3 ± 3.4 (out of 23), attitude scores were 31.1 ± 5.6 (range 8-40), and practice scores were 35.1 ± 4.4 (range 8-40). Positive attitudes (OR = 1.235, 95% CI: 1.162-1.311, P < 0.001) and aged 41-50 years were independently associated with higher practice scores. Those with the better practice were more likely to be older (OR = 2.603, 95% CI: 1.242-5.452, P = 0.011), nurses (OR = 2.274, 95% CI: 1.210-4.272, P = 0.011) and with junior/intermediary/vice-senior title (OR = 2.326, 95% CI: 1.030-5.255, P = 0.042; OR = 2.847, 95% CI: 1.226-6.606, P = 0.015; OR = 4.547, 95% CI: 1.806-11.452, P = 0.001, respectively). Subgroup analysis revealed significant differences in knowledge between technicians and physicians and nurses and between staff working in tertiary hospitals and non-tertiary hospitals. Knowledge is positively correlated with attitude (ß = 0.54, P < 0.001), and attitude is positively correlated with practice (ß = 0.37, P < 0.001). Attitudes significantly mediated the association between knowledge and practice (ß = 0.119, P < 0.001). Conclusion: The radiology medical workers showed moderate knowledge but good attitudes and practices of prevention and diagnosis of COVID-19. Attitudes were found to be positively associated with better practices of prevention and diagnosis of COVID-19. Attitudes significantly mediated the association between knowledge and practice.

Anxiety, depression, and sleep disturbances among people on long-term efavirenz-based treatment for HIV: a cross-sectional study in Beijing, China.

BACKGROUND: Efavirenz (EFV)-induced neuropsychiatric toxicity bothers people living with HIV (PLHIV). Neuropsychiatric adverse effects of EFV may differ by length of time on EFV-based antiretroviral treatment (ART). METHODS: A cross-sectional, single-center study was conducted at Beijing Ditan Hospital in China from June-August 2020 among ART-experienced PLHIV who were on long-term EFV-based ART. 424 eligible virological suppressed participants were enrolled and divided into four groups according to time on EFV-based ART: group A (0.5 ≤ ART < 2 year), B (2 ≤ ART < 4 year), C (4 ≤ ART < 6 year), and D (ART ≥ 6 year). The questionnaires about 12-item Short Form Health Survey (SF-12), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were administered to assess neuropsychiatric adverse events of EFV among different groups. RESULTS: Overall mental component summary scores (MCS) of SF-12 in PLHIV was 50.2, which was lower than general population. Overall prevalence of anxiety, depression and sleep disturbances was 15.6%, 15.3% and 58%, respectively. Prevalence of anxiety, depression and sleep disturbances did not vary significantly between the time-on-ART groups. Anxiety, depression, sleep disturbances had no correlation with time on EFV-based ART or CD4+ T cells counts. CONCLUSIONS: In ART-experienced PLHIV in China, neuropsychiatric adverse events exist persistently and prevalence do not significantly change with prolonged time on EFV-based ART. The prevalence of sleep disturbances was high, suggesting that clinicians should pay more attention to long-standing psychiatric health to perform early and effective interventions.