Omicron Breakthrough Infection Elicits Superior Humoral and Mucosal Immune Responses to SARS-CoV-2 Variants than an Intramuscular Booster Dose (preprint)

Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show that mild BT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary IgG and IgA levels against the Omicron Spike and enhanced reactivity to the ancestral Spike for the IgA isotype, which also reacted with SARS-CoV-1. Serum neutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for mucosal vaccines to emulate the enhanced mucosal and humoral immunity induced by Omicron without exposing individuals to the risks associated with SARS-CoV-2 infection.

Electrochemical immunosensor nanoarchitectonics with the Ag-rGO nanocomposites for the detection of receptor-binding domain of SARS-CoV-2 spike protein

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a grave threat to human life and health, it is essential to develop an efficient and sensitive detection method to identify infected individuals. This study described an electrode platform immunosensor to detect SARS-CoV-2-specific spike receptor-binding domain (RBD) protein based on a bare gold electrode modified with Ag-rGO nanocomposites and the biotin-streptavidin interaction system. The Ag-rGO nanocomposites was obtained by chemical synthesis and characterized by electrochemistry and scanning electron microscope (SEM). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to record the electrochemical signals in the electrode modification. The differential pulse voltammetry (DPV) results showed that the limit of detection (LOD) of the immunosensor was 7.2 fg mL−1 and the linear dynamic detection range was 0.015 ~ 158.5 pg mL−1. Furthermore, this sensitive immunosensor accurately detected RBD in artificial saliva with favorable stability, specificity, and reproducibility, indicating that it has the potential to be used as a practical method for the detection of SARS-CoV-2.

SCTV-UNet: A COVID-19 CT Segmentation Network Based on Attention Mechanism (preprint)

The global outbreak of COVID-19 has become an important research topic in healthcare since 2019. RT-PCR is the main method for detecting COVID-19, but the long detection time is a problem. Therefore, the pathological study of COVID-19 with CT image is an important supplement to RT-RCT. The current TVLoss based segmentation promotes the connectivity of diseased areas. However, normal pixels between some adjacent diseased areas are wrongly identified as diseased pixels. In addition, the proportion of diseased pixels in CT images is small, and the traditional BCE based U-shaped network only focuses on the whole CT without diseased pixels, which leads to blurry border and low contrast in the predicted result. In this way, this paper proposes a SCTV-UNet to solve these problems. By combining spatial and channel attentions on the encoder, more visual layer information are obtained to recognize the normal pixels between adjacent diseased areas. By using the composite function DTVLoss that focuses on the pixels in the diseased area, the problem of blurry boundary and low contrast caused by the use of BCE in traditional U-shaped networks is solved. The experiment shows that the segmentation effect of the proposed SCTV-UNet has significantly improved by comparing with the SOTA COVID-19 segmentation networks, and can play an important role in the detection and research of clinical COVID-19.

Immune response of primary and booster immunity of SARS-CoV-2 vaccination among patients with chronic liver disease: a real-world study (preprint)

Aim: The present study discussed the humoral immune response and antibody dynamics after primary and booster immunity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic liver disease (CLD) in the real world. Thus, it provided data to develop SARS-CoV-2 vaccination strategy. Methods: Patients with confirmed CLD and completed primary or booster immunity of SARS-CoV-2 vaccines were enrolled. Serological specimens were collected after primary or booster immunity of SARS-CoV-2 vaccines to detect novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD). Thus, we could evaluate the humoral immune response and antibody dynamics after primary and booster immunity of SARS-CoV-2 vaccines among patients with CLD. Simultaneously, baseline demographics, liver disease-related situations, comorbidity-related situations, SARS-CoV-2 vaccination information, and laboratory examination-related indicators of patients were collected. Results: A total of 315 patients received SARS-CoV-2 vaccines, including 223 patients who completed the primary immunity of SARS-CoV-2 vaccines, 114 patients who completed booster immunity of SARS-CoV-2 vaccines, and 22 patients who underwent the antibody detection of SARS-CoV-2 vaccines after both primary and booster immunities. The positive rate of nCoV NTAb was 59.64% in Primary and 87.72% in Booster (P<0.001). The median level of nCoV NTAb was 11.53 AU/mL in Primary and 31.98 AU/mL in Booster (P<0.001). The positive rate of nCoV S-RBD was 69.06% in Primary and 91.23% in Booster (P<0.001). The median level of nCoV S-RBD was 21.60AU/mL in Primary and 112.65 AU/mL in Booster (P<0.001). After booster immunity of SARS-CoV-2 vaccines in 22 patients, the positive rate of nCoV NTAb increased from 59.09% to 86.36%, and that of nCoV S-RBD increased from 68.18% to 90.91%. The median level of nCoV NTAb increased from 11.24 AU /mL to 59.14 AU /mL after booster immunity. The median level of nCoV S-RBD increased from 27.28 AU/mL to 219.10 AU/mL. Compared to the antibody level of primary immunity, the median level of nCoV NTAb and nCoV S-RBD in 22 patients was increased by 5.26 and 8.03 times, respectively. Among 22 patients, 9 were negative for nCoV NTAb after primary immunity, while 6 were transformed positive after booster immunity, and the positive conversion rate of nCoV NTAb was 66.7%. On the other hand, 7 patients were negative for nCoV S-RBD after primary immunity, while 5 were transformed positive after booster immunity, and the positive conversion rate of nCoV S-RBD was 71.4%. Conclusion: Patients with CLD show improved humoral immune response after completing primary and booster immunity of SARS-CoV-2 vaccines, while booster immunity further improves the positive rate and antibody level of patients with CLD. Finally, the positive conversion rate among patients with primary immunity failure also can be improved after booster immunity. Keywords: immune response; primary and booster immunity; SARS-CoV-2 vaccination; chronic liver disease

Behavioral compliance with preventive health measures for students with and without hearing disability during COVID-19 pandemic: A cross-sectional study

Background Hearing loss affects over 1.5 billion individuals worldwide. Their disability and limited access to the coronavirus (COVID-19) pandemic information make them suffer a greater degree than ordinary people. However, the quantitative studies on the implementation of behavior compliance with preventive health measures for vulnerable groups such as people with hearing disability were limited. The purpose of this study was to explore the compliance with pandemic-related protective health measures among people with hearing disability. Design A cross-sectional survey, population-based cohort study of students aged 12–26 years with and without hearing disability was conducted. Behavioral compliance with preventive health measures was collected from the general education institutions and special education schools using an online questionnaire. Logistic regression and structural equation model were used to determine the associations among the demographic variables, different degrees of mental health status and psychological impacts, and preventive health behaviors. Results Among 1,589 participants, 485 (30.5%) students are with hearing disability (SHD), and 1,104 (69.5%) students with normal hearing (SNH). The SHD has a significantly lower degree of behavioral compliance with the preventive health measures than SNH has. Hearing disability and anxiety [odds ratio (OR) = 1.54–1.76, p < 0.05] are risk factors for avoiding sharing of utensils during mealtime. Hearing disability, male sex, father's education level, mother's profession, bedtime after 11:00 p.m., anxiety, and depression (OR = 1.45–2.95, p < 0.05) are risk factors for hand hygiene. Male sex (OR = 2.13, p < 0.001) is risk factor and being aged below 18 years old (OR = 0.62, p = 0.03) is protective factor for wearing masks. Exercise (OR = 0.32–0.70, p < 0.01) is the most protective factor for preventive health behaviors. Mediating effect of mental health status and psychological impacts between hearing level and the compliance with the preventive health measures was −0.044 (95% CI: −0.068 to −0.027). Conclusions To reduce the risk of contraction, update pandemic information, essential communication services, extra assistance, and support should be provided to these disabled persons who are more susceptible to a public health emergency.

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants (preprint)

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Reproduction number estimation and epidemic analysis of coronavirus disease 2019 in Shandong Province based on poisson process. (Special Issue: Spatio-temporal dynamics analysis, risk assessment and emergency management for COVID-19 epidemic.) [Chinese]

Objective: To explore the epidemic dynamics of coronavirus disease 2019(COVID-19)in Shandong Province, and to provide a scientific basis for the future prevention and control of new outbreaks of COVID-19 and other emerging infectious diseases.

An intranasal influenza virus-vectored vaccine blocks SARS-CoV-2 replication in respiratory tissues of mice and hamsters (preprint)

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, blocked 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.

Study workplace space occupancy: a review of measures and technologies

Purpose>The purpose of this paper is to review the use of technologies for measuring space occupancy to guide the selection of appropriate tools for workplace post-occupancy evaluation (POE) studies. The authors focus on how actual space occupancy was measured in previous studies and the pros and cons of the different technologies and tools. This paper also addresses research gaps and directions for future research.Design/methodology/approach>The space occupancy measures/tools are categorized based on the three types of technologies: environmental/ambient sensors, wearable sensors/smartphones and computer vision. A total of 50 studies are reviewed to identify the capabilities and limitations of these measurements.Findings>Based on review results, the authors propose that although sensor technology can be a useful addition to the measures/tools list, a comprehensive review of the research goal, the occupants' behavior, and the environmental settings' characteristics should be conducted beforehand. Selecting appropriate technology is critical for collecting the proper behavioral data type, with a lower level of surveillance and increased validity.Originality/value>This paper urges critical thinking about existing occupancy measures/tools across various fields, to inform the adoption and creation of new building occupancy measures. The knowledge of emerging sensor technology allows researchers to better study the temporal patterns of occupant behavior over extended periods and in a wide range of settings.

Non-targeted characterization of dissolved organic matter from a wastewater treatment plant by FT-ICR-MS: A case study of hospital sewage

Hospitals generate large volumes of wastewater. Dissolved organic matter (DOM) in wastewater effluent can act as precursors of disinfection by-products, transporter of pollutants, and affect the performance of treatment plants. This study aims to characterize the composition of DOM in medical wastewater and investigate the selectivity of the hospital treatment plant in the removal of DOM. DOM was characterized by Fourier-transform ion-cyclotron resonance mass spectrometry (FT-ICR-MS) and excitation-emission matrix fluorescence spectroscopy (EEMs). DOM of medical wastewater was dominated by aliphatic and highly unsaturated compounds, a feature that is remarkably different from that of natural DOM. In the membrane bioreactor (MBR) unit, more CHNO compounds and highly unsaturated compounds were formed. After disinfection, the highly unsaturated and humic-like compounds were reduced, accompanying a decrease in aromaticity. After reverse osmosis, the highly unsaturated and CHO compounds were concentrated and removed. These steps were complementary in the removal of DOM, suggesting effective transformation and elimination of DOM. This study contributes to a better understanding of the features of DOM in medical wastewater and treatment plant performance in the removal of DOM, which is indispensable for the large-scale design and application of technologies for hospital wastewater treatment, especially in the context of the COVID-19 pandemic.

Trends in secondary inorganic aerosol pollution in China and its responses to emission controls of precursors in wintertime

The Chinese government recently proposed ammonia (NH3) emission reductions (but without a specific national target) as a strategic option to mitigate fine particulate matter (PM2.5) pollution. We combined a meta-analysis of nationwide measurements and air quality modeling to identify efficiency gains by striking a balance between controlling NH3 and acid gas (SO2 and NOx) emissions. We found that PM2.5 concentrations decreased from 2000 to 2019, but annual mean PM2.5 concentrations still exceeded 35 µg m-3 at 74 % of 1498 monitoring sites during 2015–2019. The concentration of PM2.5 and its components were significantly higher (16 %–195 %) on hazy days than on non-hazy days. Compared with mean values of other components, this difference was more significant for the secondary inorganic ions SO42-, NO3-, and NH4+ (average increase 98 %). While sulfate concentrations significantly decreased over this period, no significant change was observed for nitrate and ammonium concentrations. Model simulations indicate that the effectiveness of a 50 % NH3 emission reduction for controlling secondary inorganic aerosol (SIA) concentrations decreased from 2010 to 2017 in four megacity clusters of eastern China, simulated for the month of January under fixed meteorological conditions (2010). Although the effectiveness further declined in 2020 for simulations including the natural experiment of substantial reductions in acid gas emissions during the COVID-19 pandemic, the resulting reductions in SIA concentrations were on average 20.8 % lower than those in 2017. In addition, the reduction in SIA concentrations in 2017 was greater for 50 % acid gas reductions than for the 50 % NH3 emission reductions. Our findings indicate that persistent secondary inorganic aerosol pollution in China is limited by emissions of acid gases, while an additional control of NH3 emissions would become more important as reductions of SO2 and NOx emissions progress.

Rapid differentiation of SARS-CoV-2 variants on a nanotechnology enhanced DNA-chip (preprint)

With the persistence of the COVID-19 pandemic caused primarily by constant viral mutations, rapid identification of different lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by large-scale screening at the point-of-care could be key to monitoring and assessing viral evolutions. Herein, we developed a Fluorescence Enhanced Microarray for Multiplex Analysis of Nucleic acids (FEMMAN) for detecting 8 SARS-CoV-2 variants simultaneously in ~ 3 hours without the need of RNA extraction, opening the possibility of point-of-care testing of multiple SARS-CoV-2 variants while reducing the cost significantly to ~ $ 7 per sample from ~ $100 by Next-Generation Sequencing (NGS). Combined with isothermal amplification, the multiplexed RNA assay achieved single-copy detection sensitivity and single nucleotide variant (SNV) distinction owing to the nanotechnology based plasmonic gold (pGOLD) near-infrared fluorescence enhancing platform. Probing 10 targets of three mutational hotspots in S gene, we differentiated 8 viral lineages (Wild type, Alpha, Beta, Gamma, Delta, Lambda, Mu, and Omicron) of SARS-CoV-2, validated using nasopharyngeal swabs obtained from 127 individuals, achieving a 100% sensitivity and 100% specificity in SARS-CoV-2 detection, and a 91.1% concordance with NGS in variant identification. The scalable, multiplexed FEMMAN assay could shift the paradigm of COVID-19 diagnostic and surveillance from positive/negative assessments to simultaneous lineage identification in large-scale screening, greatly facilitating the global monitoring of SARS-CoV-2 variants.

Predictors of all-cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS-CoV-2 (preprint)

Background: Identification of shared and divergent predictors of clinical severity across respiratory viruses may support clinical decision-making and resource planning in the context of a novel or re-emergent respiratory pathogen. Methods: We conducted a retrospective cohort study to identify predictors of 30-day all-cause mortality following hospitalization with influenza (N=45,749; 2011-09 to 2019-05), respiratory syncytial virus (RSV, N=24,345; 2011-09 to 2019-04), or SARS-CoV-2 (N=8,988; 2020-03 to 2020-12; pre-vaccine) using population-based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude and confidence intervals of risk ratios to identify shared and divergent predictors of mortality. Results: 3,186 (7.0%), 697 (2.9%) and 1,880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS-CoV-2, respectively. Common predictors of increased mortality included: older age, male sex, residence in a long-term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS-CoV-2. Few comorbidities were associated with mortality among patients with SARS-CoV-2 as compared to those with influenza or RSV. Conclusions: Our findings may help identify patients at highest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local preventions and therapeutics to communities with high prevalence of risk factors.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial (preprint)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level (preprint)

Cardiac manifestations are commonly observed in COVID-19 patients and prominently contributed to overall mortality. Human myocardium could be infected by SARS-CoV-2, and human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are susceptible to SARS-CoV-2 infection. However, molecular mechanisms of SARS-CoV-2 gene-induced injury and dysfunction of human CMs remain elusive. Here, we find overexpression of three SARS-CoV-2 coding genes, Nsp6, Nsp8 and M, could globally compromise transcriptome of hPSC-CMs. Integrated transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with hPSC-CMs of Nsp6, Nsp8 or M overexpression identified concordantly activated genes enriched into apoptosis and immune/inflammation responses, whereas reduced genes related to heart contraction and functions. Further, Nsp6, Nsp8 or M overexpression induce prominent apoptosis and electrical dysfunctions of hPSC-CMs. Global interactome analysis find Nsp6, Nsp8 and M all interact with ATPase subunits, leading to significantly reduced cellular ATP level of hPSC-CMs. Finally, we find two FDA-approved drugs, ivermectin and meclizine, could enhance the ATP level, and ameliorate cell death and dysfunctions of hPSC-CMs overexpressing Nsp6, Nsp8 or M. Overall, we uncover the global detrimental impacts of SARS-CoV-2 genes Nsp6, Nsp8 and M on the whole transcriptome and interactome of hPSC-CMs, define the crucial role of ATP level reduced by SARS-CoV-2 genes in CM death and functional abnormalities, and explore the potentially pharmaceutical approaches to ameliorate SARS-CoV-2 genes-induced CM injury and abnormalities.

Safety and immunogenicity of a heterologous boost with a recombinant vaccine, NVSI-06-07, in the inactivated vaccine recipients from UAE: a phase 2 randomised, double-blinded, controlled clinical trial (preprint)

Background: The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. Methods: This study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. Findings: A total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20.47%) participants in the heterologous boost groups and 177 (19.64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89.96% - 97.52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36.80% - 81.75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21.01 - 63.85 folds from baseline to 28 days post-boosting vaccination, whereas only 4.20 - 16.78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37.91 (95%CI, 30.35-47.35), however, a significantly higher level of neutralizing antibodies with GMT 292.53 (95%CI, 222.81-384.07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. Interpretation: Our findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV.

Automated assessment of disease severity of COVID-19 using artificial intelligence with synthetic chest CT (preprint)

Background: Triage of patients is important to control the pandemic of coronavirus disease 2019 (COVID-19), especially during the peak of the pandemic when clinical resources become extremely limited. Purpose: To develop a method that automatically segments and quantifies lung and pneumonia lesions with synthetic chest CT and assess disease severity in COVID-19 patients. Materials and Methods: In this study, we incorporated data augmentation to generate synthetic chest CT images using public available datasets (285 datasets from "Lung Nodule Analysis 2016"). The synthetic images and masks were used to train a 2D U-net neural network and tested on 203 COVID-19 datasets to generate lung and lesion segmentations. Disease severity scores (DL: damage load; DS: damage score) were calculated based on the segmentations. Correlations between DL/DS and clinical lab tests were evaluated using Pearson's method. A p-value < 0.05 was considered as statistical significant. Results: Automatic lung and lesion segmentations were compared with manual annotations. For lung segmentation, the median values of dice similarity coefficient, Jaccard index and average surface distance, were 98.56%, 97.15% and 0.49 mm, respectively. The same metrics for lesion segmentation were 76.95%, 62.54% and 2.36 mm, respectively. Significant (p << 0.05) correlations were found between DL/DS and percentage lymphocytes tests, with r-values of -0.561 and -0.501, respectively. Conclusion: An AI system that based on thoracic radiographic and data augmentation was proposed to segment lung and lesions in COVID-19 patients. Correlations between imaging findings and clinical lab tests suggested the value of this system as a potential tool to assess disease severity of COVID-19.

Unsupervised COVID-19 Lesion Segmentation in CT Using Cycle Consistent Generative Adversarial Network (preprint)

COVID-19 has become a global pandemic and is still posing a severe health risk to the public. Accurate and efficient segmentation of pneumonia lesions in CT scans is vital for treatment decision-making. We proposed a novel unsupervised approach using cycle consistent generative adversarial network (cycle-GAN) which automates and accelerates the process of lesion delineation. The workflow includes lung volume segmentation, "synthetic" healthy lung generation, infected and healthy image subtraction, and binary lesion mask creation. The lung volume volume was firstly delineated using a pre-trained U-net and worked as the input for the later network. The cycle-GAN was developed to generate synthetic "healthy" lung CT images from infected lung images. After that, the pneumonia lesions are extracted by subtracting the synthetic "healthy" lung CT images from the "infected" lung CT images. A median filter and K-means clustering were then applied to contour the lesions. The auto segmentation approach was validated on two public datasets (Coronacases and Radiopedia). The Dice coefficients reached 0.748 and 0.730, respectively, for the Coronacases and Radiopedia datasets. Meanwhile, the precision and sensitivity for lesion segmentationdetection are 0.813 and 0.735 for the Coronacases dataset, and 0.773 and 0.726 for the Radiopedia dataset. The performance is comparable to existing supervised segmentation networks and outperforms previous unsupervised ones. The proposed unsupervised segmentation method achieved high accuracy and efficiency in automatic COVID-19 lesion delineation. The segmentation result can serve as a baseline for further manual modification and a quality assurance tool for lesion diagnosis. Furthermore, due to its unsupervised nature, the result is not influenced by physicians' experience which otherwise is crucial for supervised methods.

Relationship between parental rearing styles, self-directed learning ability and depressive symptoms among high school students during the COVID-19 outbreak

Objective: Explored the characteristics of parental rearing styles, and its association with depressive symptoms and the self-directed learning ability among high school students during COVID-19 epidemic, while providing a basis for family intervention in the area of adolescent mental health and students' learning abilities.

Declined eGFR Associated With Poor Prognosis in COVID-19 Patients in Wuhan, China: A Retrospective Cohort Study (preprint)

Background: Increasing evidence revealed that kidney was one of the targets of SARS-CoV-2. However, the incidences of kidney abnormalities were significantly different, from 0·5 to 75·4% in coronavirus disease 2019 (COVID-19) patients. The association of kidney injury with prognosis remain controversial.Methods: In this retrospective cohort study, laboratory confirmed COVID-19 in patients with severe type were enrolled. Demographic, clinical, and laboratory data were collected. Association of estimated glomerular filtration rate (eGFR) with 28-days mortality was analyzed.Findings: The total 28-days mortality of hospitalization was 22·3% (79/354). Non-survivors had a significantly declined eGFR levels than survivors (75·95 [IQR: 47·22,92·84] ml/min/1·73m2 vs. 96·43 [IQR: 84·11,108·47] ml/min/1·73m2, P <0·0001). The 28-days mortality in declined eGFR group (<90 ml/min/1·73m2) was significantly higher than that in normal eGFR group (38·5% vs. 10·7%, P <0·0001). Multivariate logistic regression revealed that the independent risk factors of 28-days outcome included lower eGFR (OR: 3·97, 95%CI: 1·42-11·11), elevated WBC (OR: 7·08, 95%CI: 3·15-15·90), lymphopenia (OR: 2·58, 95%CI: 1·21-5·49), and IL-6 (OR: 7·90, 95%CI: 2·19-28·49). Kaplan-Meier analysis indicated the survival disadvantage in patients with declined eGFR. ROC curve showed the eGFR cut-off value for predicting 28-days death was 82·2 μmol/L, with the sensitivity of 76·7%, and specialty of 66·3%.Interpretation: Declined eGFR was associated with poor prognosis, and could be used an independent risk factor of 28-days mortality in COVID-19 patients. Early detection, and surveillance for eGFR may benefit to identify patients with high-risk of progression.Funding Information: Program of Key Talents of Medical Science in Jiangsu Province, Suzhou science and technology development plan.Declaration of Interests: The authors have declared that no conflict of interest exists.Ethics Approval Statement: This study was approved by the institutional review boards at the First Affiliated Hospital of Soochow University and Wuhan Tongji Hospital. As COVID-19 is an emerging infectious disease, the written informed consent was exempted.