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Conversion disorder-called functional neurological symptom disorder in the DSM-5 -has roots that trace back to antiquity. The term conversion , originating from psychoanalysis, signifies the appearance of physical symptoms as an effort to resolve or convey unconscious and distressing intrapsychic conflicts- "converting" them from manifesting in the mind to manifesting in the body. Despite efforts made in elucidating the neurobiological etiologies of functional neurological symptom disorder, a psychodynamic lens remains indispensable in understanding the patient. This article presents two patients who developed functional neurological symptom disorder, one after a COVID-19 vaccination and one in the context of long COVID. A discussion follows on the intrapersonal, interpersonal, and systemic etiological factors that predispose, precipitate, and perpetuate COVID-related functional neurological symptom disorder. We elaborate on psychodynamic psychological processes and conflicts that may unfold between patients with COVID-related functional neurological symptom disorder and their health care providers. We also share suggestions on how a consultation-liaison psychiatry team may offer support to the primary treating team to facilitate a therapeutic space within which patients with COVID-related functional neurological symptom disorder may recover.

The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN-stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper respiratory tract and least favorable in the lower respiratory cell line, and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals., Importance: Comparative analysis of infections by SARS-CoV-2 ancestral virus and variants of concern, including Alpha, Beta, Delta, and Omicron, indicated that variants were selected for efficiency in replication. In infections of patient-derived primary nasal cultures grown at air-liquid interface to model upper respiratory infection, Omicron reached the highest titers at early time points, a finding that was confirmed by parallel population sampling studies. While all infections overcame dsRNA-mediated host responses, infections with Omicron induced the strongest interferon and interferon-stimulated gene response. In both primary nasal cultures and lower respiratory cell line, infections by Delta were most damaging to the cells as indicated by syncytia formation, loss of cell barrier integrity, and nasal ciliary function., Competing Interests: The authors declare no conflict of interest.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since its emergence in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV infections including murine coronavirus and Middle East respiratory syndrome (MERS)-CoV. To determine how nsp15 functions during SARS-CoV-2 infection, we constructed a recombinant SARS-CoV-2 (nsp15 mut ) expressing catalytically inactivated nsp15, which we show promoted increased dsRNA accumulation. Infection with SARS-CoV-2 nsp15 mut led to increased activation of the IFN signaling and PKR pathways in lung-derived epithelial cell lines and primary nasal epithelial air-liquid interface (ALI) cultures as well as significant attenuation of replication in ALI cultures compared to wild-type virus. This replication defect was rescued when IFN signaling was inhibited with the Janus activated kinase (JAK) inhibitor ruxolitinib. Finally, to assess nsp15 function in the context of minimal (MERS-CoV) or moderate (SARS-CoV-2) innate immune induction, we compared infections with SARS-CoV-2 nsp15 mut and previously described MERS-CoV nsp15 mutants. Inactivation of nsp15 had a more dramatic impact on MERS-CoV replication than SARS-CoV-2 in both Calu3 cells and nasal ALI cultures suggesting that SARS-CoV-2 can better tolerate innate immune responses. Taken together, SARS-CoV-2 nsp15 is a potent inhibitor of dsRNA-induced innate immune response and its antagonism of IFN signaling is necessary for optimal viral replication in primary nasal ALI cultures., Competing Interests: Competing interests statement:S.R.W. consults for Powell Gilbert LLP. N.A.C. consults for GSK, AstraZeneca, Novartis, Sanofi/Regeneron. N.A.C. has US Patent “Therapy and Diagnostics for Respiratory Infection” (10,881,698 B2, WO20913112865) and a licensing agreement with GeneOne Life Sciences.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety., Methods: A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR)., Results: We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR., Conclusion: Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic., Competing Interests: None

Background: The coronavirus disease 2019 (COVID-19) caused a global pandemic, with potential severity. We aimed to investigate whether genetically predicted gut microbiome is associated with susceptibility and severity of COVID-19 risk., Methods: Mendelian randomization (MR) analysis of two sets with different significance thresholds was carried out to infer the causal relationship between the gut microbiome and COVID-19. SNPs associated with the composition of the gut microbiome (n = 5,717,754) and with COVID-19 susceptibility (n = 14,328,058), COVID-19 severity (n = 11,707,239), and COVID-19 hospitalization (n = 12,018,444) from publicly available genome-wide association studies (GWAS). The random-effect inverse variance weighted (IVW) method was used to determine causality. Three more MR techniques-MR Egger, weighted median, and weighted mode-and a thorough sensitivity analysis were also used to confirm the findings., Results: IVW showed that 18 known microbial taxa were causally associated with COVID-19. Among them, six microbial taxa were causally associated with COVID-19 susceptibility; seven microbial taxa were causally associated with COVID-19 severity ; five microbial taxa were causally associated with COVID-19 hospitalization. Sensitivity analyses showed no evidence of pleiotropy or heterogeneity. Then, the predicted 37 species of the gut microbiome deserve further study., Conclusion: This study found that some microbial taxa were protective factors or risky factors for COVID-19, which may provide helpful biomarkers for asymptomatic diagnosis and potential therapeutic targets for COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Xie, Feng, Zhang, Xia, Tan, Chen, Su, Zhang, Feng and Guo.)

Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as FcγRIIa- and FcγRIIIa-binding antibodies, in plasma from two-dose BNT162b2-vaccine recipients and mild-COVID-19 convalescent subjects obtained during the first wave using a custom-designed bead-based 39-plex array. IgG-recognition and FcγR-binding antibodies were decreased against the RBD of Beta and Omicron, as well as point mutation G446S, found in several Omicron sub-variants as compared to wild type. Notably, while there was a profound decrease in ACE2 inhibition against Omicron, FcγR-binding antibodies were less affected, suggesting that Fc functional antibody responses may be better retained against the RBD of Omicron in comparison to neutralization. Furthermore, while measurement of RBD-ACE2-binding affinity via biolayer interferometry showed that all VOC RBDs have enhanced affinity to human ACE2, we demonstrate that human ACE2 polymorphisms, E35K (rs1348114695) has reduced affinity to VOCs, while K26R (rs4646116) and S19P (rs73635825) have increased binding kinetics to the RBD of VOCs, potentially affecting virus-host interaction and, thereby, host susceptibility. Collectively, our findings provide in-depth coverage of the impact of RBD mutations on key facets of host-virus interactions., (© 2023. The Author(s).)

COVID-19 vaccination programmes have helped reduce deaths and morbidity from the pandemic and allowed for the resumption of normal life. However, vaccine hesitancy remains an issue even with recurrent surges in COVID-19 cases due to new SARS-CoV-2 variants. Purpose: To elucidate psychosocial factors that contribute to our understanding of vaccine hesitancy. 676 Participants in Singapore took part in an online survey on vaccine hesitancy and uptake between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness and hesitancy factors were collected. The responses were analyzed using structural equation modeling (SEM). The study found that confidence in the COVID-19 vaccines and risk perception of the COVID-19 situation are significantly associated with vaccination intention, while vaccination intention is also significantly associated with reported vaccination status. Additionally, certain chronic medical conditions moderate the relationship between vaccine confidence/risk perception and vaccine intention. This study contributes to our understanding of factors behind vaccination uptake which can help anticipate challenges to future vaccination campaigns for the next pandemic., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The purpose of this study was to evaluate available evidence on the association between the human oral microbiota and coronavirus disease 2019 (COVID-19) and summarize relevant data obtained during the pandemic., Methods: We searched EMBASE, PubMed, and the Cochrane Library for human studies published up to October 2022. The main outcomes of the study were the differences in the diversity (α and β) and composition of the oral microbiota at the phylum and genus levels between patients with laboratory-confirmed SARS-CoV-2 infection (CPs) and healthy controls (HCs). We used the Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA) database, Protein-protein interaction (PPI) network (STRING) and Gene enrichment analysis (Metascape) to evaluate the expression of dipeptidyl peptidase 4 (DPP4) (which is the cell receptor of SARS CoV-2) in oral tissues and evaluate its correlation with viral genes or changes in the oral microbiota., Results: Out of 706 studies, a meta-analysis of 9 studies revealed a significantly lower alpha diversity (Shannon index) in CPs than in HCs (standardized mean difference (SMD): -0.53, 95% confidence intervals (95% CI): -0.97 to -0.09). Subgroup meta-analysis revealed a significantly lower alpha diversity (Shannon index) in older than younger individuals (SMD: -0.54, 95% CI: -0.86 to -0.23/SMD: -0.52, 95% CI: -1.18 to 0.14). At the genus level, the most significant changes were in Streptococcus and Neisseria, which had abundances that were significantly higher and lower in CPs than in HCs based on data obtained from six out of eleven and five out of eleven studies, respectively. DPP4 mRNA expression in the oral salivary gland was significantly lower in elderly individuals than in young individuals. Spearman correlation analysis showed that DPP4 expression was negatively correlated with the expression of viral genes. Gene enrichment analysis showed that DPP4-associated proteins were mainly enriched in biological processes, such as regulation of receptor-mediated endocytosis of viruses by host cells and bacterial invasion of epithelial cells., Conclusion: The oral microbial composition in COVID-19 patients was significantly different from that in healthy individuals, especially among elderly individuals. DPP4 may be related to viral infection and dysbiosis of the oral microbiome in elderly individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tan, Zhong, Liu, Chen, Zhao, Zhao, Dusenge, Feng, Ye, Hu, Ou-Yang, Zhou, Guo and Feng.)

The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary human nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal [Severe acute respiratory syndrome (SARS)-CoV-2 and Middle East respiratory syndrome-CoV (MERS-CoV)] and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures, though replication is differentially modulated by temperature. Infections conducted at 33 °C vs. 37 °C (reflective of temperatures in the upper and lower airway, respectively) revealed that replication of both seasonal HCoVs (HCoV-NL63 and -229E) is significantly attenuated at 37 °C. In contrast, SARS-CoV-2 and MERS-CoV replicate at both temperatures, though SARS-CoV-2 replication is enhanced at 33 °C late in infection. These HCoVs also diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not. Treatment of nasal cultures with type 2 cytokine IL-13 to mimic asthmatic airways differentially impacts HCoV receptor availability as well as replication. MERS-CoV receptor DPP4 expression increases with IL-13 treatment, whereas ACE2, the receptor used by SARS-CoV-2 and HCoV-NL63, is down-regulated. IL-13 treatment enhances MERS-CoV and HCoV-229E replication but reduces that of SARS-CoV-2 and HCoV-NL63, reflecting the impact of IL-13 on HCoV receptor availability. This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.

Purpose: To figure out whether enhanced recovery after surgery (ERAS) could effectively improve the prognosis of colorectal cancer (CRC) patients and reduce hospitalization expenses under the shadow of COVID-19, furthermore to alleviate the current situation of medical resource for the whole society. Methods: Patients who underwent CRC surgery in the department of gastrointestinal surgery of the First Affiliated Hospital from January 2020 to March 2022 were retrospectively enrolled. According to protocol adherence, all patients were divided into the ERAS group and the non-ERAS group. Short-term outcomes were compared between the two groups. Results: A total of 918 patients were enrolled in the study. Based on protocol adherence ≥70%, 265 patients were classified into the ERAS group and the other 653 patients were classified into the non-ERAS group. Patients in the ERAS group had shorter operation time ( P  < .01), less intraoperative blood loss ( P  < .01), shorter overall hospital stay ( P  < .01) and postoperative hospital stay ( P  < .01), less hospital costs ( P  < .01), earlier first flatus ( P  < .01), earlier first stool ( P  < .01), earlier food tolerance ( P  < .01), and lower postoperative complications ( P  < .01). Univariate and multivariate logistic regression analysis manifested that ERAS and cerebrovascular disease were predictive factors of postoperative overall complications. In univariate analyses, cerebrovascular disease ( P  = .033, OR = 2.225, 95% CI = 1.066-4.748), time of the surgery ( P  = .026, OR = 1.417, 95% CI = 1.043-1.925), and ERAS ( P  < .01, OR = 0.450, 95% CI = 0.307-0.661) were predictive factors. Furthermore, in the multivariate analysis, ERAS ( P  < .01, OR = 0.440, 95% CI = 0.295-0.656) and cerebrovascular disease ( P  = .016, OR = 2.575, 95% CI = 1.190-5.575) were independent predictive factors of postoperative overall complications. Conclusion: In summary, under the impact of the COVID-19 pandemic, ERAS could still reduce the financial burden of patients and reduce the incidence of short-term postoperative complications. However, whether the effects of ERAS were enhanced after the pandemic and the long-term outcomes of CRC obey ERAS remained to be further explored.

The ingestion and accumulation of microplastics is a serious threat to the health and survival of humans and other organisms given the increasing use of daily-use plastic products, especially during the COVID-19 pandemic. However, whether direct microplastic contamination from plastic packaging is a threat to human health remains unclear. We analyzed the market demand for plastic packaging in Asia-Pacific, North America, and Europe and identified the commonly used plastic food packaging products. We found that food containers exposed to high-temperature released more than 10 million microplastics per mL in water. Recycled plastic food packaging was demonstrated to continuously leach micro- and nanoplastics. In vitro cell engulfing experiments revealed that both micro- and nanoplastic leachates are readily taken up by murine macrophages without any preconditioning, and that short-term microplastic exposure may induce inflammation while exposure to nanoplastic substantially suppressed the lysosomal activities of macrophages. We demonstrated that the ingestion of micro- and nanoplastics released from food containers can exert differential negative effects on macrophage activities, proving that the explosive growth in the use of plastic packaging can poses significant health risks to consumers., (Copyright © 2022. Published by Elsevier B.V.)

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein 269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A ∗ 02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as "variants of concern," was not recognized by the large CD8 T cell response seen across cohorts of HLA A ∗ 02 + convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants., Competing Interests: Declaration of interests The authors declare no competing interests in regard to this work., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The coronavirus disease 2019 (COVID-19) pandemic has impacted nursing home care and activities in profound ways. We sought to understand whether the COVID-19 pandemic had any impact on hospital admissions of nursing home residents., Methods: A retrospective analysis of hospital admissions of nursing home residents to a tertiary general hospital in Singapore during the COVID-19 pandemic in 2020 was conducted and compared to admissions in the preceding year. Patients' demographics, length of stay, primary diagnosis on admission, death and causes of death were recorded., Results: Our study found reduced number of hospital admissions of nursing home residents to a tertiary hospital in Singapore. There was a significant decrease in pneumonia (p < 0.001) and fall (p = 0.001) as a primary diagnosis on admission and a decrease in pneumonia as the cause of death (p < 0.001) for nursing home residents admitted to hospital during the COVID-19 pandemic., Conclusions: This suggests that measures implemented during the pandemic may have impacted outcomes of nursing home residents. Further study is warranted to lead to practise changing outcomes for nursing home settings., (© 2021 AJA Inc.)

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into humans in 2012, causing highly lethal respiratory disease. The severity of disease may be, in part, because MERS-CoV is adept at antagonizing early innate immune pathways—interferon (IFN) production and signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L)—activated in response to viral double-stranded RNA (dsRNA) generated during genome replication. This is in contrast to severe acute respiratory syndrome CoV-2 (SARS-CoV-2), which we recently reported to activate PKR and RNase L and, to some extent, IFN signaling. We previously found that MERS-CoV accessory proteins NS4a (dsRNA binding protein) and NS4b (phosphodiesterase) could weakly suppress these pathways, but ablation of each had minimal effect on virus replication. Here we investigated the antagonist effects of the conserved coronavirus endoribonuclease (EndoU), in combination with NS4a or NS4b. Inactivation of EndoU catalytic activity alone in a recombinant MERS-CoV caused little if any effect on activation of the innate immune pathways during infection. However, infection with recombinant viruses containing combined mutations with inactivation of EndoU and deletion of NS4a or inactivation of the NS4b phosphodiesterase promoted robust activation of dsRNA-induced innate immune pathways. This resulted in at least tenfold attenuation of replication in human lung–derived A549 and primary nasal cells. Furthermore, replication of these recombinant viruses could be rescued to the level of wild-type MERS-CoV by knockout of host immune mediators MAVS, PKR, or RNase L. Thus, EndoU and accessory proteins NS4a and NS4b together suppress dsRNA-induced innate immunity during MERS-CoV infection in order to optimize viral replication.

Objective: Achieving high vaccination rates is key to containing the coronavirus disease 2019 (COVID-19). This study evaluated the factors associated with uptake of the COVID-19 vaccine., Methods: Six hundred and seventy-six respondents were surveyed online between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness and hesitancy factors were collected., Results: Approximately 54.6% of the respondents had received the COVID-19 vaccination. Age (p = 0.001), males (OR 1.7, 95% CI 1.1-2.6, p = 0.026), ethnicity (p = 0.004), occupation (p = 0.003)), working in healthcare (OR 6.1, 95% CI 2.8-13.2, p < 0.001), smoking (OR 3.3, 95% CI 1.3-8.8, p = 0.014), seeing vaccination as a social responsibility (OR 3.8, 95% CI 1.2-12.0, p = 0.022) and believing the vaccine is important to end the COVID-19 pandemic (OR 2.7, 95% CI 1.1-6.1, p = 0.020) were associated with greater vaccination uptake., Conclusion: Social responsibility and well-being of collective society are important values associated with vaccine uptake in an Asian society. Understanding factors behind vaccine uptake can help advise public health measures and strategies to achieve high levels of vaccination.

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017., Competing Interests: The authors have declared that no competing interests exist.

Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel noncovalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease (M pro ) by employing a scalable high-throughput virtual screening (HTVS) framework and a targeted compound library of over 6.5 million molecules that could be readily ordered and purchased. Our HTVS framework leverages the U.S. supercomputing infrastructure achieving nearly 91% resource utilization and nearly 126 million docking calculations per hour. Downstream biochemical assays validate this M pro inhibitor with an inhibition constant ( K i ) of 2.9 μM (95% CI 2.2, 4.0). Furthermore, using room-temperature X-ray crystallography, we show that MCULE-5948770040 binds to a cleft in the primary binding site of M pro forming stable hydrogen bond and hydrophobic interactions. We then used multiple μs-time scale molecular dynamics (MD) simulations and machine learning (ML) techniques to elucidate how the bound ligand alters the conformational states accessed by M pro , involving motions both proximal and distal to the binding site. Together, our results demonstrate how MCULE-5948770040 inhibits M pro and offers a springboard for further therapeutic design.

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to respiratory failure and multi-organ failure or death. The pathogenesis of SARS-CoV-2 infection is attributed to a complex interplay between virus and host immune response. It involves activation of multiple inflammatory pathways leading to hyperinflammation and cytokine storm, resulting in tissue damage, acute respiratory distress syndrome (ARDS) and multi-organ failure. Accumulating evidence has raised concern over the long-term health effects of COVID-19. Importantly, the neuroinvasive potential of SARS-CoV-2 may have devastating consequences in the brain. This review provides a conceptual framework on how the virus tricks the host immune system to induce infection and cause severe disease. We also explore the key differences between mild and severe COVID-19 and its short- and long-term effects, particularly on the human brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Komarasamy and RMT Balasubramaniam.)

Aim: To assess the prevalence of burnout, secondary traumatic stress, and compassion satisfaction and explore their impacts on self-reported hand hygiene among medical aid teams in the COVID-19 period in Wuhan, China., Design: Cross-sectional study., Method: A total of 1,734 healthcare workers from 17 medical aid teams were surveyed. The survey included burnout, secondary traumatic stress and compassion satisfaction measured by the professional quality of life scale and self-reported hand hygiene. Data were collected between 5-7 March 2020. Multiple regression analyses were performed., Results: Burnout and secondary trauma stress were at low and average levels, and compassion satisfaction was at average and high levels. Burnout was negatively associated with hand hygiene, while compassion satisfaction was positively associated. Hospital administrators should pay attention to burnout and compassion satisfaction to improve infection control behaviours. Management of healthcare workers in our study may be constructive in emerging infectious diseases., (© 2021 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 10 4 -fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2., Competing Interests: Competing interest statement: P.P., A.A., and W.-H.T. are inventors on a provisional patent covering the nanobodies described in this manuscript., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: The severity and outcome of COVID-19 cases has been associated with the percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), lactic acid (LA), and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear., Methods: We retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity., Findings: CRP, PCT, IL-6, LYM%, and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP, and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe, and moderate types and between survivors and non-survivors., Conclusions: CRP, PCT, IL-6, LYM%, and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19., Funding: This study was supported in part by awards from the National Natural Science Foundation of China, the Foundation and Frontier Research Project of Chongqing, and the Chongqing Youth Top Talent Project., Competing Interests: The authors declare no competing interests., (© 2020 Elsevier Inc.)

Purpose: We present the implementation of e-learning in the Master of Medical Physics programme at the University of Malaya during a partial lockdown from March to June 2020 due to the COVID-19 pandemic., Methods: Teaching and Learning (T&L) activities were conducted virtually on e-learning platforms. The students' experience and feedback were evaluated after 15 weeks., Results: We found that while students preferred face-to-face, physical teaching, they were able to adapt to the new norm of e-learning. More than 60% of the students agreed that pre-recorded lectures and viewing videos of practical sessions, plus answering short questions, were beneficial. Certain aspects, such as hands-on practical and clinical experience, could never be replaced. The e-learning and study-from-home environment accorded a lot of flexibility. However, students also found it challenging to focus because of distractions, lack of engagement and mental stress. Technical problems, such as poor Internet connectivity and limited data plans, also compounded the problem., Conclusion: We expect e-learning to prevail in future. Hybrid learning strategies, which includes face-to-face classes and e-learning, will become common, at least in the medical physics programme of the University of Malaya even after the pandemic., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Introduction: The outbreak of COVID-19 has spread worldwide. The evidence about risk factors of healthcare workers who infected COVID-19 is limited. This study aims to describe characteristics and influencing factors of the COVID-19 infection in healthcare workers., Methodology: The study was performed among COVID-19 infected and uninfected healthcare workers in three hospitals in Wuhan. A total of 325 healthcare workers participated; among them 151 COVID-19-infected healthcare workers were included. Characteristics of infected healthcare workers, and influencing factors including exposure histories, the use of protective equipment in different risk conditions and areas, perceptions, emotions, satisfactions and educations were described and analyzed., Results: Healthcare workers got infected clustered mostly in the physical examination center. When performing general operations on confirmed or suspected patients, the use of protective equipment including the effectiveness of masks (p < 0.001), gloves (p < 0.001); and the use of gloves (p < 0.001), suits (p < 0.001), gowns (p < 0.001), shoe covers (p < 0.001), and hats (p < 0.001) were protective factors. The use of protective equipment was a protective factor in most cases. Negative emotions and dissatisfaction to the hospital response were associated with the increased risk of infection., Conclusions: The use of protective equipment, emotions and satisfactions to hospital responses are key COVID-19-infected factors. The awareness, the supply and the use of protective equipment, the layout of departments and other environmental and management factors should be strictly equipped. In addition, hospitals should also pay attention to emotions and satisfaction of healthcare workers., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Xiaoquan Lai, Qian Zhou, Xinping Zhang, Li Tan.)

This study highlights a survey on 5783 kindergarten teachers' occupational commitment and its influencing factors in the socioeconomic context of China during the COVID-19 pandemic. Data were collected through the WenJuanXing public online platform. Quantitative analysis results showed that kindergarten teachers' occupational commitment was optimistic on the whole during this period, among which the affective commitment and the normative commitment were satisfactory, but the continuing commitment needed to be strengthened. The type of kindergartens, the personnel affiliation, the educational background, and the professional post of kindergarten teachers had significant impacts on their occupational commitment. The income reduction was negatively correlated with and predictive of kindergarten teachers' occupational commitment. Anti-epidemic action and career confidence were positively correlated with and predictive of kindergarten teachers' occupational commitment. Furthermore, anti-epidemic action, income reduction, and career confidence had joint predictive effects on kindergarten teachers' occupational commitment. More related backgrounds and suggestions have been discussed.

In spite of the sudden onset of the COVID-19 pandemic, many instructors who used team-based pedagogies shifted them online rather than suspending them entirely, but with limited time and resources. To examine the difference in team dynamics and outcomes for courses in Spring 2019 and Spring 2020 of over 1500 first-year engineering students per semester, Wilcoxon signed-rank tests and random forests method were used. Results show that students reported less improvement in team-member effectiveness, lower psychological safety, and less satisfaction in the semester with the emergency transition. However, students also reported lower conflict. The most important factor predicting project grades shifted from 'Interacting with teammates' to 'Having relevant knowledge, skills, and abilities' amid the emergency shift, accompanied by a reduction in team interdependence. In spite of the collection of data during an emergency transition, the foundation of face-to-face interaction before moving to virtual cooperation represents a useful contribution to research that has focused exclusively on virtual learning circumstances. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relations between young children's negative emotions and their mothers' mental health during the COVID‐19 pandemic. Background: The COVID‐19 pandemic caused the public a certain degree of psychological symptoms, and family environments and relations have been changed dramatically as a result. The relations between young children's negative emotions and their mothers' mental health have not been sufficiently determined for the context of a pandemic or other large‐scale crises. Method: A survey was administrated on 8119 Chinese mothers of 3‐ to 6‐year‐old children with the Symptom Checklist 90 and the Child Negative Emotion Questionnaire. Results: The canonical correlation results indicated that there were covariation trends between young children's anger and their mother's obsessive–compulsive symptoms and hostility, children's fear and mothers' phobic anxiety, and children's tension and mothers' interpersonal sensitivity and depression. These correlations were all positively significant. Conclusion: During the COVID‐19 pandemic, the predictive power of young children's negative emotions to their mothers' mental health was greater than that of the reverse. Implications: This study provides a scientific guidance on the regulation of young children's negative emotions and the improvement of mothers' mental health during the pandemic as well as potential emergencies in the future. [ABSTRACT FROM AUTHOR]

• Twelve air samples and 355 surface samples from a hospital were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). • Only one air sample, which was obtained during an intubation procedure, tested positive. • A low level of surface contamination was found, and most occurred on high-touch surfaces. • No association was found between surface contamination and patient characteristics. Few studies have explored air and surface contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare settings. Air and surface samples were collected from the isolation wards and intensive care units designated for coronavirus disease 2019 (COVID-19) patients. Clinical data and the results of nasopharyngeal specimen and serum antibody testing were also collected for the patient sample. A total of 367 air and surface swab samples were collected from the patient care areas of 15 patients with mild COVID-19 and nine patients with severe/critical COVID-19. Only one air sample taken during the intubation procedure tested positive. High-touch surfaces were slightly more likely to be contaminated with SARS-CoV-2 RNA than low-touch surfaces. Contamination rates were slightly higher near severe/critical patients than near mild patients, although this difference was not statistically significant (p > 0.05). Surface contamination was still found near the patients with both positive IgG and IgM. Air and surface contamination with viral RNA was relatively low in these healthcare settings after the enhancement of infection prevention and control. Environmental contamination could still be found near seroconverted patients, suggesting the need to maintain constant vigilance in healthcare settings to reduce healthcare-associated infection during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The article discusses the COVID-19 outbreak has placed immense pressure on national healthcare systems globally, to increase bed capacity, protect healthcare workers and care for vulnerable groups. Topics include older adults face barriers to the adoption of telehealth services such as cost, trust of technology, design aod user interface challenges; and the COVID-19 pandemic has in fact led to greater uptake of telehealth services for older adults.

• Nasopharyngeal swab showed higher positive rate than oropharyngeal swab. • Nasopharyngeal swab from male showed higher positive rate than female. • The consistency between from nasopharyngeal and oropharyngeal swabs were poor. Since the outbreak of coronavirus disease (COVID-19) in Wuhan in December 2019, by March 10, 2020, a total of 80,932 confirmed cases have been reported in China. Two consecutively negative RT-PCR test results in respiratory tract specimens is required for the evaluation of discharge from hospital, and oropharyngeal swabs were the most common sample. However, false negative results occurred in the late stage of hospitalization, and avoiding false negative result is critical essential. We reviewed the medical record of 353 patients who received tests with both specimens simultaneously, and compared the performance between nasopharyngeal and oropharyngeal swabs. Of the 353 patients (outpatients, 192; inpatients, 161) studied, the median age was 54 years, and 177 (50.1%) were women. Higher positive rate (positive tests/total tests) was observed in nasopharyngeal swabs than oropharyngeal swabs, especially in inpatients. Nasopharyngeal swabs from inpatients showed higher positive rate than outpatients. Nasopharyngeal swabs from male showed higher positive rate than female, especially in outpatients. Detection with both specimens slightly increased the positive rate than nasopharyngeal swab only. Moreover, the consistency between from nasopharyngeal and oropharyngeal swabs were poor (Kappa = 0.308). In conclusion, our study suggests that nasopharyngeal swabs may be more suitable than oropharyngeal swab at this stage of COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

Since coronavirus disease 2019 (COVID-19) is a serious new worldwide public health crisis with significant morbidity and mortality, effective therapeutic treatments are urgently needed. Drug repurposing is an efficient and cost-effective strategy with minimum risk for identifying novel potential treatment options by repositioning therapies that were previously approved for other clinical outcomes. Here, we used an integrated network-based pharmacologic and transcriptomic approach to screen drug candidates novel for COVID-19 treatment. Network-based proximity scores were calculated to identify the drug–disease pharmacological effect between drug–target relationship modules and COVID-19 related genes. Gene set enrichment analysis (GSEA) was then performed to determine whether drug candidates influence the expression of COVID-19 related genes and examine the sensitivity of the repurposing drug treatment to peripheral immune cell types. Moreover, we used the complementary exposure model to recommend potential synergistic drug combinations. We identified 18 individual drug candidates including nicardipine, orantinib, tipifarnib and promethazine which have not previously been proposed as possible treatments for COVID-19. Additionally, 30 synergistic drug pairs were ultimately recommended including fostamatinib plus tretinoin and orantinib plus valproic acid. Differential expression genes of most repurposing drugs were enriched significantly in B cells. The findings may potentially accelerate the discovery and establishment of an effective therapeutic treatment plan for COVID-19 patients. [ABSTRACT FROM AUTHOR]

[Display omitted] The COVID-19 pandemic caused by SARS-CoV-2 has created an unprecedented global health emergency. As of July 2021, only three antiviral therapies have been approved by the FDA for treating infected patients, highlighting the urgent need for more antiviral drugs. The SARS-CoV-2 3CL protease (3CLpro) is deemed an attractive drug target due to its essential role in viral polyprotein processing and pathogenesis. Indeed, a number of peptidomimetic 3CLpro inhibitors armed with electrophilic warheads have been reported by various research groups that can potentially be developed for treating COVID-19. However, it is currently impossible to compare their relative potencies due to the different assays employed. To solve this, we conducted a head-to-head comparison of fifteen reported peptidomimetic inhibitors in a standard FRET-based SARS-CoV-2 3CLpro inhibition assay to compare and identify potent inhibitors for development. Inhibitor design and the suitability of various warheads are also discussed. [ABSTRACT FROM AUTHOR]