A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Inflammatory ocular events after inactivated COVID-19 vaccination.

To report potential vaccine-induced inflammatory ocular adverse events following inactivated COVID-19 vaccination. Retrospective study of patients with uveitis and other ocular complications following inactivated coronavirus disease 2019 (COVID-19) vaccination at a tertiary referral center between May 2021 and August 2021. Data collection consisted of demographic and clinical data. The study included 8 eyes of 5 patients (4 females, 1 male), with a mean age of 37.2 ± 12.5 years (range 28-59 years). Mean time between vaccination and ocular complications onset was 13.2 ± 11.9 days (range 3-30 days), including two patients after the first dose of the vaccine and 3 patients after the second dose. The cases reported were three anterior uveitis, one herpetic keratitis and iridocyclitis, and one posterior uveitis. Patients received treatment with local and/or systemic steroids and all the patients had good visual outcomes. Ocular inflammatory events may occur after vaccination with possible gender preponderance. However, they are rare and manageable. Overall, the efficacy and safety of vaccination should be emphasized.

A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape.

The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel ß-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of ß-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.

Amantadine-assembled nanostimulator enhances dimeric RBD antigen-elicited cross-neutralization against SARS-CoV-2 strains.

There is an urgent need to develop new vaccination strategies to elevate the cross-neutralization against different SARS-CoV-2 strains. In this study, we construct the spherical amantadine-assembled nanostimulator (AAS). Amantadine as immunostimulating molecules are displayed on the outermost layer of AAS. Molecular mechanism analysis reveals that AAS can activate RIG-I-like receptor (RLR) signaling pathway to increase the expression of type I interferons in vivo. AAS-mediated activation of RLR signaling pathway further promotes the maturation and proliferation of dendritic cells (DCs) and T helper cells (Ths), finally activating B cells to produce potent antibody responses. In performance evaluation experiments, the mixture of AAS and dimeric RBD significantly enhances RBD-specific humoral responses (4-fold IgG, 3.5-fold IgG2a, 3.3-fold IgG2b, 3.8-fold IgG3 and 1.3-fold IgM), in comparison to aluminum adjuvant-assistant dimeric RBD. Importantly, AAS dramatically elevates dimeric RBD-elicited cross-neutralization against different SARS-CoV-2 strains such as Wuhan-Hu-1 (9-fold), B.1.1.7 (UK variant, 15-fold), B.1.351 (South African variant, 4-fold) and B.1.617.2 (India variant, 7-fold). Our study verifies the mechanism of AAS in activating RLR signaling pathway in host immune system and highlights the power of AAS in improving antigen-elicited cross-neutralization against different SARS-CoV-2 strains.

A nanofluidic preconcentrator integrated with an aluminum-based nanoplasmonic sensor for Epstein-Barr virus detection

Epstein-Barr virus (EBV) positivity is one of the indexes for diagnosing nasopharyngeal carcinoma (NPC). Moreover, systemic inflammatory responses can easily be triggered in patients who are both EBV- and coronavirus disease 2019 (COVID-19)-positive. Development of rapid and highly sensitive EBV screening methods has become important. In this study, a nanofluidic preconcentrator integrated with a nanoslit Fano resonance biosensor was developed to detect latent membrane protein 1 (LMP1) for an EBV diagnosis. Through nanoimprinting and aluminum deposition, the low-cost nanoslit plasmonic sensing chip can be mass-produced. The nanoporous membrane was patterned on a sensing chip as an ion selective channel to concentrate LMP1 proteins. Anti-LMP1 immunoglobulin G was then modified to a sensing chip to immunosense LMP1. The Fano resonant spectrum of the capped nanoslit array produced a transmission peak followed by a dip. We recorded and analyzed the spectrum using four methods, including area, center of mass, peak value, and dip value methods. With preconcentration, a limit of detection (LOD) of 100pg/ml and a sensing range of 100pg/ml to 10µg/ml was achieved using the peak value.

Health Anxiety and Its Correlates in the General Chinese Population During the COVID-19 Epidemic.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has had an adverse impact on the mental health of the general population. This study aimed to investigate the prevalence and correlates of health anxiety (HA) in the general Chinese population to inform psychological interventions in COVID-19-affected areas. Methods: We conducted an online survey of the general population in mainland China between 6 and 17 February 2020 (N = 1,450, 69.79% female; mean age = 37.5 ± 9.1 years). The Whiteley Index-7 (WI-7), COVID-19 knowledge quiz (CKQ), Generalised Anxiety Disorder scale (GAD-7), Patient Health Questionnaire Depression Scale (PHQ-9), and socio-demographic information were surveyed using the Questionnaire-Star program. Results: The prevalence of HA, depression and anxiety were 47.3, 31.3, and 35.7%, respectively. The WI-7 score showed a significant association with age, education level, income, occupation, chronic disease and daily time focused on COVID-19. On binary logistic regression analysis, individuals with masters or higher qualification degree [odds ratio (OR) = 0.632)], older age (OR = 0.981), 2-4 h daily time focused on COVID-19 (OR = 0.684), healthcare workers (OR = 0.749, p = 0.046) and those with more COVID-19 related knowledge (OR = 0.785) showed a significantly negative association with HA. Chronic disease (OR = 1.962), depression (OR = 1.05) and anxiety (OR = 1.228) were significant risk factors for HA. Conclusions: HA was highly prevalent among the general population during the early stages of the COVID-19 outbreak. More than two-fifths of the respondents had obvious HA. Chronic disease, depression and anxiety were risk factors for HA; psychological interventions offered during the pandemic should pay particular attention to these individuals.

Workplace violence against frontline clinicians in emergency departments during the COVID-19 pandemic.

BACKGROUND: Frontline clinicians working in emergency departments (ED) were at disportionate risk of workplace violence (WPV). We investigated the prevalence of WPV and its relationship with quality of life (QOL) in this group of health professionals in China during the COVID-19 pandemic. METHODS: A cross-sectional, online study was conducted. The nine-item Workplace Violence Scale measured WPV. RESULTS: A total of 1,103 ED clinicians participated in this study. The overall prevalence of WPV against ED clinicians was 29.2% (95% CI [26.5%-31.9%]). Having family/friends/colleagues infected with COVID-19 (Odds Ratio (OR) = 1.82, P = 0.01), current smoking (OR = 2.98, P < 0.01) and severity of anxiety symptoms (OR = 1.08, P < 0.01) were independently and positively associated with WPV, while working in emergency intensive care units (OR = 0.45, P < 0.01) was negatively associated with WPV. After controlling for covariates, clinicians experiencing WPV had a lower global QOL compared to those without (F(1, 1103) = 10.9,P < 0.01). CONCLUSIONS: Prevalence of workplace violence against ED clinicians was common in China during the COVID-19 pandemic. Due to the negative impact of WPV on QOL and quality of care, timely preventive measures should be undertaken for ED clinicians.

Prevalence of depression and its associated factors among adolescents in China during the early stage of the COVID-19 outbreak.

BACKGROUND: The outbreak of the 2019 coronavirus disease outbreak (COVID-19) had a detrimental impact on adolescents' daily life and studying, which could increase the risk of depression. This study examined the prevalence of depressive symptoms (depression hereafter) among Chinese adolescents and its associated factors. METHODS: An online survey was conducted during the COVID-19 outbreak in China. Adolescents aged 11-20 years who currently lived in China were invited to participate in the study. Data were collected with the "SurveyStar" platform using the Snowball Sampling method. Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: A total of 9,554 adolescents participated in the study. The prevalence of depression was 36.6% (95% CI [35.6%-37.6%]); the prevalence of mild and moderate-severe depression was 9.2% (95% CI [8.9%-9.5%]) and 27.4% (95% CI [26.9%-27.9%]), respectively. Female gender (OR = 1.235, P < 0.001), senior secondary school grade (OR = 1.513, P < 0.001), sleep duration of <6 h/day (OR = 2.455, P < 0.001), and living in Hubei province (total number of infected cases > 10,000) (OR = 1.245, P = 0.038) were significantly associated with higher risk of depression. Concern about COVID-19 (OR = 0.632, P < 0.001), participating in distance learning (OR = 0.728, P = 0.001), sleep duration of >8 h/day (OR = 0.726, P < 0.001), exercise of >30 min/day, and study duration of ≥4 h/day (OR = 0.835, P < 0.001) were associated with lower risk of depression. CONCLUSION: Depression was common among adolescents in China during the COVID-19 outbreak. Considering the negative impact of depression on daily life and health outcomes, timely screening and appropriate interventions are urgently needed for depressed adolescents during the COVID-19 outbreak.

Combating the Infodemic: A Chinese Infodemic Dataset for Misinformation Identification.

Misinformation posted on social media during COVID-19 is one main example of infodemic data. This phenomenon was prominent in China when COVID-19 happened at the beginning. While a lot of data can be collected from various social media platforms, publicly available infodemic detection data remains rare and is not easy to construct manually. Therefore, instead of developing techniques for infodemic detection, this paper aims at constructing a Chinese infodemic dataset, "infodemic 2019", by collecting widely spread Chinese infodemic during the COVID-19 outbreak. Each record is labeled as true, false or questionable. After a four-time adjustment, the original imbalanced dataset is converted into a balanced dataset by exploring the properties of the collected records. The final labels achieve high intercoder reliability with healthcare workers' annotations and the high-frequency words show a strong relationship between the proposed dataset and pandemic diseases. Finally, numerical experiments are carried out with RNN, CNN and fastText. All of them achieve reasonable performance and present baselines for future works.

The Prevalence and Correlative Factors of Depression Among Chinese Teachers During the COVID-19 Outbreak.

Background: Epidemiological data on outbreak-associated depression of Chinese teachers are not available. This study aimed to investigate the prevalence and correlates of depression among teachers during the coronavirus disease 2019 (COVID-19) outbreak in mainland China. Methods: A large cross-sectional online survey was conducted during the COVID-19 outbreak. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). The Connor-Davidson Resilience Scale 25 (CD-RISC 25) and Perceived Stress Scale-10 (PSS-10) were used to measure the mental resilience and stress of participants. The correlative factors of depression were analyzed. Results: In this study, 1,096 teachers were analyzed with a median (range) age of 41 (20-65) years. Of them, 624 (56.9%) suffered from depression (PHQ-9 total score of >4). The multivariate analyses showed that participants with aged ≥41 years (OR = 0.752, 95% CI:0.578-0.979, p = 0.034), participating in epidemic prevention and control (OR = 1.413, 95% CI:1.070-1.867, p = 0.015), thinking prolonged school closure have bad effect (OR = 1.385, 95% CI:1.017-1.885, p = 0.038), sleep duration/day of <6 h (OR = 1.814, 95% CI:1.240-2.655, p < 0.001), physical exercise duration/day of <30 min (OR = 1.619, 95% CI:1.247-2.103, p < 0.001), spending less time with family (OR = 1.729, 95% CI: 1.063-2.655, p = 0.002), being concerned about COVID-19 (OR = 0.609, 95% CI:0.434-0.856, p = 0.004), having poor mental resilience (OR = 6.570, 95% CI:3.533-12.22, p < 0.001) and higher PSS-10 scores (OR = 9.058, 95% CI:3.817-21.50, p < 0.001) were independently associated with depression. Conclusion: During the COVID-19 outbreak, depression was common among teachers. Age, participating in epidemic prevention and control, opinions toward distant teaching and prolonged school closure, sleep duration/day, physical exercise duration, spending time with family, attitude toward COVID-19, mental resilience and stress represented the independent factors for suffering from depression.

Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus.

Effective vaccines are vital to fight against the COVID-19 global pandemic. As a critical component of a subunit vaccine, the adjuvant is responsible for strengthening the antigen-induced immune responses. Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses. Notably, even at a 5-fold lower antigen dose and with fewer injections, the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) in vitro than that of Alum-adsorbed RBD vaccine (Alu-RBD). Furthermore, we found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DCs, CD4+ and CD8+ T lymphocytes. Our findings highlight the importance of MnARK adjuvant in the design of novel coronavirus vaccines and provide a rationale strategy to design protective vaccines through promoting cellular internalization and the activation of immune-related pathways.

COVID-19 infodemic on Chinese social media: A 4P framework, selective review and research directions

During the outbreak of the COVID-19 (2019 coronavirus disease), misinformation related to the virus spread rapidly online and have led to serious difficulties in controlling the disease. The term infodemic is coined to outline the bad effect from the extensive dissemination of misinformation during the outbreak. With regards to this phenomenon, the World Health Organization emphasized the need to fight against infodemic and asked all countries not only to make efforts in slowing down the spread of the COVID-19 but also in countering the risk caused by infodemic. Due to its negative impact, this paper analyzes infodemic on Chinese social media at the initial stage of the COVID-19 outbreak and presents a 4P framework standing for the four features of Chinese infodemic: Prevention Attention, Problem Orientation, Patterns Interaction and Points Globalization. Furthermore, a selective review of existing datasets in the neural networks domain is synthesized based on the 4P framework. Finally, research directions, including recommendations, about constructing a large-scale dataset for Chinese infodemic automatic detection are proposed.

Gut microbiota in antiviral strategy from bats to humans: a missing link in COVID-19.

Bats are a potential natural reservoir for SARS-CoV-2 virus and other viruses detrimental to humans. Accumulated evidence has shown that, in their adaptation to a flight-based lifestyle, remodeling of the gut microbiota in bats may have contributed to immune tolerance to viruses. This evidence from bats provides profound insights into the potential influence of gut microbiota in COVID-19 disease in humans. Here, we highlight recent advances in our understanding of the mechanisms by which the gut microbiota helps bats tolerate deadly viruses, and summarize the current clinical evidence on the influence of gut microbiota on the susceptibility to SARS-CoV-2 infection and risk of COVID-19 leading to a fatal outcome. In addition, we discuss the implications of gut microbiota-targeted approaches for preventing infection and reducing disease severity in COVID-19 patients.

Corrigendum: Longitudinal Analysis of T and B Cell Receptor Repertoire Transcripts Reveal Dynamic Immune Response in COVID-19 Patients.

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Longitudinal Analysis of T and B Cell Receptor Repertoire Transcripts Reveal Dynamic Immune Response in COVID-19 Patients.

Severe COVID-19 is associated with profound lymphopenia and an elevated neutrophil to lymphocyte ratio. We applied a novel dimer avoidance multiplexed polymerase chain reaction next-generation sequencing assay to analyze T (TCR) and B cell receptor (BCR) repertoires. Surprisingly, TCR repertoires were markedly diminished during the early onset of severe disease but recovered during the convalescent stage. Monitoring TCR repertoires could serve as an indicative biomarker to predict disease progression and recovery. Panoramic concurrent assessment of BCR repertoires demonstrated isotype switching and a transient but dramatic early IgA expansion. Dominant B cell clonal expansion with decreased diversity occurred following recovery from infection. Profound changes in T cell homeostasis raise critical questions about the early events in COVID-19 infection and demonstrate that immune repertoire analysis is a promising method for evaluating emergent host immunity to SARS-CoV-2 viral infection, with great implications for assessing vaccination and other immunological therapies.

An adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques.

The rapid spread of coronavirus SARS-CoV-2 greatly threatens global public health but no prophylactic vaccine is available. Here, we report the generation of a replication-incompetent recombinant serotype 5 adenovirus, Ad5-S-nb2, carrying a codon-optimized gene encoding Spike protein (S). In mice and rhesus macaques, intramuscular injection with Ad5-S-nb2 elicits systemic S-specific antibody and cell-mediated immune (CMI) responses. Intranasal inoculation elicits both systemic and pulmonary antibody responses but weaker CMI response. At 30 days after a single vaccination with Ad5-S-nb2 either intramuscularly or intranasally, macaques are protected against SARS-CoV-2 challenge. A subsequent challenge reveals that macaques vaccinated with a 10-fold lower vaccine dosage (1 × 1010 viral particles) are also protected, demonstrating the effectiveness of Ad5-S-nb2 and the possibility of offering more vaccine dosages within a shorter timeframe. Thus, Ad5-S-nb2 is a promising candidate vaccine and warrants further clinical evaluation.

Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers.

The coronavirus disease 2019 (COVID-19) pandemic has led to dramatic changes in oncology practice. It is currently unknown whether programmed death 1 (PD-1) blockade therapy affects severity of illness from COVID-19 in patients with cancer. To address this uncertainty, we examined consecutive patients with lung cancers who were diagnosed with COVID-19 and examined severity on the basis of no or prior receipt of PD-1 blockade. Overall, the severity of COVID-19 in patients with lung cancer was high, including need for hospitalization in more than half of patients and death in nearly a quarter. Prior PD-1 blockade was, as expected, associated with smoking status. After adjustment for smoking status, PD-1 blockade exposure was not associated with increased risk of severity of COVID-19. PD-1 blockade does not appear to affect the severity of COVID-19 in patients with lung cancers. SIGNIFICANCE: A key question in oncology practice amidst the COVID-19 pandemic is whether PD-1 blockade therapy affects COVID-19 severity. Our analysis of patients with lung cancers supports the safety of PD-1 blockade treatment to achieve optimal cancer outcomes.This article is highlighted in the In This Issue feature, p. 1079.