T a g g e d E n dBackground: The coronavirus disease 2019 (COVID-19) is spreading rapidly, bringing pressure and challenges to nursing staff. Objective: To explore the psychology of nurses caring for COVID-19 patients. Methods: Using a phenomenological approach, we enrolled 20 nurses who provided care for COVID-19 patients in the First Affiliated Hospital of Henan University of Science and Technology from January 20, to February 10, 2020. The interviews were conducted face-to-face or by telephone and were analysed by Colaizzi's 7-step method. Results: The psychological experience of nurses caring for COVID-19 patients can be summarized into 4 themes. First, negative emotions present in early stage consisting of fatigue, discomfort, and helplessness was caused by high-intensity work, fear and anxiety, and concern for patients and family members. Second, self-coping styles included psychological and life adjustment, altruistic acts, team support, and rational cognition. Third, we found growth under pressure, which included increased affection and gratefulness, development of professional responsibility, and self-reflection. Finally, we showed that positive emotions occurred simultaneously with negative emotions. Conclusions: During an epidemic outbreak, positive and negative emotions of the front-line nurses interweaved and coexisted. In the early stage, negative emotions were dominant and positive emotions appeared gradually. Self-coping styles and psychological growth played an important role in maintaining mental health of nurses.
Biomolecular condensates have emerged as an important subcellular organizing principle 1 . Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm 2,3 . IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation 4,5 . Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers 6 .RSV is a major cause of respiratory illness in young children, the older people and individuals who are immunocompromised worldwide 7,8 . Currently, multiple targets are pursued for the development of a safe and effective therapy to treat RSV infections 9 .In infected cells, RSV induces the formation of cytoplasmic IBs, in which nucleoprotein (N), phosphoprotein (P), polymerase L, the transcription factor M2-1 and viral genomic RNA are concentrated. We recently demonstrated that IBs are 'viral factories' in which viral RNA synthesis occurs 3 . The morphology of IBs suggests that they are condensates formed by liquid-liquid phase separation (LLPS). A recent study showed that N and P were sufficient to drive the formation of pseudo-IB condensates through LLPS in vitro, both in cells and in biochemical assays 10 . However, these N-P pseudo-IB condensates are not functional, as they do not shelter RNA synthesis and do not reflect the complexity of IBs in virus-infected cells, which have multiple compartments. Strikingly similar in size and phase organization to the nucleolus condensate 11 , RSV IBs are multiphasic and contain a sub-compartment called the IB-associated granule (IBAG), which is composed of newly synthesized viral mRNA and M2-1 3,12 . Condensates have emerged as an important subcellular organizing principle 1 . An important question in anti-viral drug developmentand medicinal chemistry more generally-is whether these condensates are druggable. In principle, a drug that dissolved or hardened would prevent viral replication. Neither mechanism has yet been reported. Chemical analogues without hedgehog antagonismWe previously identified the hedgehog (HH) pathway antagonist cyclopamine (CPM) as a potent inhibitor of RSV replication 13 . Inhibition of Sonic hedgehog (SHH) signalling is an unwanted feature of CPM as an RSV inhibitor. On the basis of the binding model of the Smoothe...
What is already known about this topic?Though coronavirus disease 2019 (COVID-19) has largely been controlled in China, several outbreaks of COVID-19 have occurred from importation of cases or of suspected virus-contaminated products. Though several outbreaks have been traced to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated on the outer packaging of cold chain products, live virus has not been obtained. What is added by this report?In September 2020, two dock workers were detected as having asymptomatic SARS-CoV-2 infection using throat swabs during routine screening in Qingdao, China. Epidemiological information showed that the two dock workers were infected after contact with contaminated outer packaging, which was confirmed by genomic sequencing. Compared to the Wuhan reference strain, the sequences from the dock workers and the package materials differed by 12-14 nucleotides. Furthermore, infectious virus from the cold chain products was isolated by cell culture, and typical SARS-CoV-2 particles were observed under electron microscopy. What are the implications for public health practice?The international community should pay close attention to SARS-CoV-2 transmission mode through cold chain, build international cooperative efforts in response, share relevant data, and call on all countries to take effective prevention and control measures to prevent virus contamination in cold-chain food production, marine fishing and processing, transportation, and other operations.
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