Antiviral polysaccharide and antiviral peptide delivering nanomaterials for prevention and treatment of SARS-CoV-2 caused COVID-19 and other viral diseases.

Antiviral peptides and antiviral polysaccharides can play a major role in the prevention and treatment of emerging viral health problems. These antiviral compounds are biocompatible, environmentally friendly, non-toxic, and cost-effective, yet are poorly water soluble and vulnerable to enzymatic (protease) degradation within the aggressive intercellular microenvironment. Therefore, they should be properly protected and delivered to viruses and host cells by the well-designed nanocarriers that mimic viruses in terms of size, morphology, and smart function. This literature review is meant to introduce the latest advances (mainly within the past five years) in antiviral nano-assemblies comprising antiviral peptides or antiviral polysaccharides. To the best of our knowledge, there is no similar study in the literature that has solely and sufficiently investigated such antiviral nanomaterials partially or totally derived from nature. The rational classification of microorganism-, plant-, and animal-derived antiviral polysaccharide and antiviral peptide delivering nanomaterials and exploration of their relevant applications will clarify the promising capacity of these state-of-the-art materials for a number of technologies developed to inactivate viruses.

Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus.

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR-MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR-MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7-dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re-modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS-CoV-2 and all tested variants.

Advanced Vaccine Design Strategies against SARS-CoV-2 and Emerging Variants.

Vaccination is the most cost-effective means in the fight against infectious diseases. Various kinds of vaccines have been developed since the outbreak of COVID-19, some of which have been approved for clinical application. Though vaccines available achieved partial success in protecting vaccinated subjects from infection or hospitalization, numerous efforts are still needed to end the global pandemic, especially in the case of emerging new variants. Safe and efficient vaccines are the key elements to stop the pandemic from attacking the world now; novel and evolving vaccine technologies are urged in the course of fighting (re)-emerging infectious diseases. Advances in biotechnology offered the progress of vaccinology in the past few years, and lots of innovative approaches have been applied to the vaccine design during the ongoing pandemic. In this review, we summarize the state-of-the-art vaccine strategies involved in controlling the transmission of SARS-CoV-2 and its variants. In addition, challenges and future directions for rational vaccine design are discussed.

Analysis of SIQR type mathematical model under Atangana-Baleanu fractional differential operator.

In the given manuscript, the fractional mathematical model for the current pandemic of COVID-19 is investigated. The model is composed of four agents of susceptible (S), infectious (I), quarantined (Q) and recovered (R) cases respectively. The fractional operator of Atangana-Baleanu-Caputo (ABC) is applied to the considered model for the fractional dynamics. The basic reproduction number is computed for the stability analysis. The techniques of existence and uniqueness of the solution are established with the help of fixed point theory. The concept of stability is also derived using the Ulam-Hyers stability technique. With the help of the fractional order numerical method of Adams-Bashforth, we find the approximate solution of the said model. The obtained scheme is simulated on different fractional orders along with the comparison of integer orders. Varying the numerical values for the contact rate ζ, different simulations are performed to check the effect of it on the dynamics of COVID-19.

A Heterologous Challenge Rescues the Attenuated Immunogenicity of SARS-CoV-2 Omicron BA.1 Variant in Syrian Hamster Model.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein, which may cause shifts of immunogenicity, so as to result in immune escape and breakthrough infection among the already infected or vaccinated populations. It is unclear whether infection with Omicron could generate adequate cross-variant protection. To investigate this possibility, we used Syrian hamsters as an animal model for infection of SARS-CoV-2. The serum from Omicron BA.1 variant-infected hamsters showed a significantly lower neutralization effect against infection of the same or different SARS-CoV-2 variants than the serum from Beta variant-infected hamsters. Furthermore, the serum from Omicron BA.1 variant-infected hamsters were insufficient to protect against rechallenge of SARS-CoV-2 Prototype, Beta and Delta variants and itself. Importantly, we found that rechallenge with different SARS-CoV-2 lineages elevated cross-variant serum neutralization titers. Overall, our findings indicate a weakened immunogenicity feature of Omicron BA.1 variant that can be overcome by rechallenge of a different SARS-CoV-2 lineages. Our results may lead to a new guideline in generation and use of the vaccinations to combat the pandemic of SARS-CoV-2 Omicron variant and possible new variants. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant causes breakthrough infections among convalescent patients and vaccinated populations. However, Omicron does not generate robust cross-protective responses. Here, we investigate whether heterologous SARS-CoV-2 challenge is able to enhance antibody response in a sensitive animal model, namely, Syrian hamster. Of note, a heterologous challenge of Beta and Omicron BA.1 variant significantly broadens the breadth of SARS-CoV-2 neutralizing responses against the prototype, Beta, Delta, and Omicron BA.1 variants. Our findings confirm that vaccination strategy with heterologous antigens might be a good option to protect against the evolving SARS-CoV-2.

Determinants and mechanisms driving energy-saving behaviours of long-stay hotel guests: Comparison of leisure, business and extended-stay residential cases

The global hospitality industry is fast-turning sustainable and environmentally friendly. Behaviour-driven energy conservation is an emerging green hotel operation strategy to support this change. The long-stay accommodation services have gained momentum in the hospitality sector since the COVID-19 pandemic. However, the characteristics of long-stay hotel guests are often overlooked in sustainable interventions. Based on an empirical survey in China, this study aims to explore the factors driving energy-saving behaviours of long-stay hotel guests and to compare their effects on guests for different visiting purposes (leisure, business, and extended-stay resident). The analysis indicates that attitude, personal norm and place attachment present a direct contribution to energy-saving behaviour. Besides, the results support that attitude and personal norm connect environmental values and energy-saving behaviour. Both altruistic and biospheric values have positive effects, while egoistic values seem to play a negative role. Biospheric values have stronger impact on attitude and personal norm of business guests. Place attachment has a stronger influence on extended-stay residents while its contribution to energy-saving behaviours of business guests is smaller than other guests. Besides, leisure guests are more sensitive to moral obligations. This research sheds novel lights on the psychological perspectives of the observed heterogeneity of energy-saving behaviours of hotel guests with different visiting purposes. The findings provide hotel operators with a novel theoretical reference for targeted energy-saving interventions to promote energy-saving actions of long-term hotel guests. The study, therefore, can contribute to sustainable tourism policymaking and behaviour-driven hotel energy management.

Nasal irrigation efficiently attenuates SARS-CoV-2 Omicron infection, transmission and lung injury in the Syrian hamster model.

Recently, a new variant lineage of SARS-CoV-2, namely Omicron, became the dominant global circulating strain. The multiple antigenic mutations of Omicron largely decrease the efficiency of current vaccines and neutralizing antibodies, which highlights the need for more potent and reachable medical countermeasures. Here, we hypothesize that direct viral clearance by nasal irrigation might be a convenient and alternative option, and perform proof-of-concept experiments in the Syrian hamster model. Interestingly, Omicron shows a different dynamic in the changes of viral RNA, viral titers, and proinflammatory cytokines in nasal rinsing samples when compared with the prototype. Meanwhile, the levels of viral load and proinflammatory cytokines in nasal rinsing samples can indicate the severity of lung injury. Of note, daily nasal irrigation efficiently attenuates inflammation and lung injury in Omicron-infected hamsters by decreasing the viral loads in the respiratory tract organs. Moreover, daily nasal irrigation effectively suppresses viral transmission by close contact.

Infection, pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile, adult and aged Syrian hamsters.

The new predominant circulating SARS-CoV-2 variant, Omicron, can robustly escape current vaccines and neutralizing antibodies. Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants, its pathogenicity in different age groups has not been well elucidated. Here, we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters, with more body weight loss, respiratory tract viral burden, and lung injury in these hamsters than in adult hamsters. Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection, whereas aged hamsters show excessive proinflammatory cytokine expression, delayed viral clearance, and aggravated lung injury. Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters. Overall, the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.

HEPA filters for airliner cabins: State of the art and future development.

The airliner cabin environment is very important to the health of passengers and crew members, and the use of high-efficiency particulate air (HEPA) filters for recirculated air in the environmental control systems (ECS) is essential for the removal of airborne particles such as SARS CoV-2 aerosols. A HEPA filter should be high efficiency, low-pressure drop, high dust-holding capacity (DHC), lightweight, and strong for use in aircraft. We conducted an experimental study on 23 HEPA filters with glass fiber media that are used in different commercial airliner models. The tested filters had a median filtration efficiency of >99.97% for particles with a diameter of 0.3-0.5 µm, a pressure drop of 134-412 Pa at rated airflow rate, and a DHC of 32.2-37.0 g/m2 . The use of nanofiber media instead of glass fiber media can reduce the pressure drop by 66.4%-94.3% and significantly increase the quality factor by analysis of literature data. The disadvantages of poor fire resistance and small DHC can be overcome by the use of flame-retardant polymers and fiber structural design. As a new lightweight and environmentally friendly filter material, nanofiber media could be used as air filters in ECS in the future.

Real-time fluorescent RT-PCR-based nucleic acid detection methods for SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is caused by infection by SARS-COV-2.. The main clinical manifestations are fever, cough, fatigue, respiratory distress, and even death. The virus is highly contagious, spreads mainly through droplets, and has wrought havoc upon human health, national economies, and public-health systems worldwide. The clinical diagnosis is based mainly on clinical manifestations, computed tomography of the chest, and laboratory examinations. For the latter, real-time fluorescent reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and genome sequencing are the "gold standard" for the diagnosis. Choosing a rapid and efficient method for pathogen detection has a key role in improving the diagnosis rate, cure rate, as well as reducing morbidity and mortality. Compared with genome sequencing, RT-qPCR has the advantages of simple operation and short cycle, which is particularly important for the diagnosis of SARS-CoV-2. Here, we review the sensitivity, specificity, and practicality of different methods of RT-qPCR for detection of the nucleic acids of SARS-CoV-2, and provide a reference for clinicians to choose more efficient detection methods for nucleic acids.

Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation.

Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were found to bind MASP-2, a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein. Complement hyperactivation was also observed in SARS-CoV-2-infected patients. Either blocking the N protein:MASP-2 interaction, MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo. Altogether, these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.

Result of SARS-CoV-2 nucleic acid test for aerosol in a designated COVID-19 hospital

OBJECTIVE: To collect aerosol from isolation wards of a designated COVID-19 hospital and conduct the nucleic acid test so as to provide scientific basis for prevention and control of COVID-19. METHODS: The air aerosol specimens were collected from layout sites in the isolation wards of the hospital by using bioaerosol collector, and the COVID-19 nucleic acid test was carried out for all of the specimens by using fluorescent polymerase chain reaction(PCR) and digital PCR. RESULTS: A total of 86 aerosol samples were collected, all of which were tested negative for the fluorescent PCR, the result of the digital PCR test showed that 14 air aerosol samples were tested positive for COVID-19 nucleic acid, with the detection rate 16.28%. The toilets of the patients and taking-off area of protective supplies of healthcare workers were the major places where the specimens were tested positive. The positive rate of nucleic acid test was significantly higher in in intensive care units than in common wards, however, there was no significant difference in the positive rate of nucleic acid among the aerosol specimens in different wards(?-2=7.871, P=0.248);there was no significant difference in the positive rate of nucleic acid of aerosol between the patients with CT value more than 30 and the patients with CT value no more than 30(?-2=0.232, P=0.630). CONCLUSION: There are still viral nucleic acids in the air aerosol of the isolation wards during the middle and late disease course of the COVID-19 patients, but the copy number of novel coronavirus is not large in the specimens. The detection rate of the viral nucleic acid is high in the aerosol of the wards that are crowed and poorly ventilated and are associated with the cases. It is necessary for the health care workers to take good care of themselves, keep the environment well ventilated and do a good job in environmental cleaning and disinfection and air purification.

SARS-CoV-2 N Protein Antagonizes Stress Granule Assembly and IFN Production by Interacting with G3BPs to Facilitate Viral Replication.

SARS-CoV-2 is the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19) and poses a significant threat to global health. N protein (NP), which is a major pathogenic protein among betacoronaviruses, binds to the viral RNA genome to allow viral genome packaging and viral particle release. Recent studies showed that NP antagonizes interferon (IFN) induction and mediates phase separation. Using live SARS-CoV-2 viruses, this study provides solid evidence showing that SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming G3BP1-mediated antiviral innate immunity. G3BP1 conditional knockout mice (g3bp1fl/fL, Sftpc-Cre) exhibit significantly higher lung viral loads after SARS-CoV-2 infection than wild-type mice. Our findings contribute to the growing body of knowledge regarding the pathogenicity of NPSARS-CoV-2 and provide insight into new therapeutics targeting NPSARS-CoV-2. IMPORTANCE In this study, by in vitro assay and live SARS-CoV-2 virus infection, we provide solid evidence that the SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming antiviral innate immunity mediated by G3BP1 in A549 cell lines and G3BP1 conditional knockout mice (g3bp1-cKO) mice, which provide in-depth evidence showing the mechanism underlying NP-related SARS-CoV-2 pathogenesis through G3BPs.

Rampant C-to-U deamination accounts for the intrinsically high mutation rate in SARS-CoV-2 spike gene.

The high mutation rate of SARS-CoV-2 largely complicates our control of the pandemic. In particular, it is currently unclear why the spike (S) gene has an extraordinarily high mutation rate among all SARS-CoV-2 genes. By analyzing the occurrence of fixed synonymous mutations between SARS-CoV-2 and RaTG13, and profiling the DAF (derived allele frequency) of polymorphic synonymous sites among millions of worldwide SARS-CoV-2 strains, we found that both fixed and polymorphic mutations show higher mutation rates in the S gene than other genes. The majority of mutations are C-to-T, representing the APOBEC-mediated C-to-U deamination instead of the previously proposed A-to-I deamination. Both in silico and in vivo evidence indicated that the S gene is more likely to be single-stranded compared to other SARS-CoV-2 genes, agreeing with the APOBEC preference of ssRNA. We conclude that the single-stranded property of the S gene makes it a favorable target for C-to-U deamination, leading to its excessively high mutation rate compared to other non-S genes. In conclusion, APOBEC, rather than ADAR, is the "editor-in-chief" of SARS-CoV-2 RNAs. This work helps us to understand the molecular mechanism underlying the mutation and evolution of SARS-CoV-2, and we believe it will contribute to the control of the pandemic.

Relationship between risk perception of COVID-19 and job withdrawal among Chinese nurses: The effect of work-family conflict and job autonomy.

AIM: The aim of this study was to examine the mediating role of work-family conflict and the moderating role of job autonomy on the association between risk perception of COVID-19 and job withdrawal among Chinese nurses during the initial disease outbreak. BACKGROUND: Nurses' job withdrawal can not only reduce the quality and efficiency of care but also give rise to turnover during the COVID-19 pandemic. Thus, it is essential to clarify how and when the risk perception of COVID-19 influences the job withdrawal behaviours of nurses and to provide guidelines for reducing nurses' job withdrawal. METHODS: A two-wave study was conducted among 287 Chinese nurses from 11 COVID-19-designated hospitals during the initial outbreak of the disease from March through April 2020. Data on the risk perception of COVID-19, job autonomy and work-family conflict were collected at time 1, and 1 month later, job withdrawal data were collected at time 2. Model 4 and Model 14 from SPSS macro PROCESS were used to test the mediating effect of work-family conflict and the moderating effect of job autonomy, respectively. RESULTS: Work-family conflict mediated 60.54% of the relationship between risk perception of COVID-19 and job withdrawal. Job autonomy positively moderated the relation between work-family conflict and job withdrawal (ß = 0.12, P < 0.01). CONCLUSION: Risk perception of COVID-19 influenced nurses' job withdrawal through work-family conflict. Job autonomy exaggerated the association between work-family conflict and job withdrawal. IMPLICATIONS FOR NURSING MANAGEMENT: Managers should provide more supportive resources to help nurses cope with the risk of COVID-19 to decrease work-family conflict and job withdrawal, and they should strengthen supervision over the work processes of nurses.

Searching therapeutic strategy of new coronavirus pneumonia from angiotensin-converting enzyme 2: the target of COVID-19 and SARS-CoV.

Since December 2019, the infection of the new coronavirus (COVID-19) caused an outbreak of new coronavirus pneumonia in Wuhan, China, and caused great public concern. Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. In addition, ACE2 is a potential therapeutic target. This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.

Positive impacts of e-aid cognitive behavioural therapy on the sleep quality and mood of nurses on site during the COVID-19 pandemic.

OBJECTIVE: To investigate the positive impact of e-aid cognitive behavioural therapy on the sleep quality, anxiety, and depression of nurses on site during the COVID-19 pandemic. METHODS: Nurses on site at the Tianjin Medical University General Hospital Airport Site experiencing insomnia, anxiety and depression during the COVID-19 prevention and control period, from February 2020 to April 2021, were selected and divided into either an e-aid cognitive behavioural therapy (eCBT-I) group or a control group using a randomized grouping method. The eCBT-I group was given standard eCBT-I for 6 weeks; the control group did not get any intervention. The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) were used to evaluate the sleep quality of the subjects. The Generalized Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire (PHQ-9) were used to assess the subjects' anxiety and depression. Changes in sleep quality, anxiety and depression before and after treatment were compared between the two groups. RESULTS: Of 118 nurses randomized, the PSQI and ISI scores within the eCBT-I group (n=60) were significantly lower after treatment (5.9 ± 3.9, 6.7 ± 4.5) than before treatment (10.4 ± 3.5, 12.4 ± 4.7) (p <0.05). Compared to the scores of the control group (n=58) (9.1 ± 3.9, 10.6 ± 4.1), the PSQI and ISI scores in the eCBT-I group (5.9 ± 3.9, 6.7 ± 4.5) were lower after treatment (p <0.05). The GAD-7 and PHQ-9 scores in the eCBT-I group were all lower after treatment (3.7±3.4, 4.2±4.1) than before treatment (6.7±4.9, 7.7±5.1) (p <0.05). Compared with subjects in the control group (7.1±5.6, 7.3±5.1), subjects in the eCBT-I group (3.7±3.4, 4.2±4.1) had lower scores on the GAD-7 and PHQ-9 scales after treatment (p <0.05). CONCLUSION: eCBT-I improved the sleep quality of frontline nurses during the COVID-19 prevention and control period and relieved anxiety and depression.

Optically computed phase microscopy for quantitative dynamic imaging of label-free cells and nanoparticles.

Numerous drug delivery systems based on nanoparticles have been developed, such as those used in BioNTech/Pfizer's and Moderna's Covid vaccines. Knowledge on mechanical interactions between cells and nanoparticles is critical to advance the efficiency and safety of these drug delivery systems. To quantitatively track the motion of cell (transparent) and nanoparticles (nontransparent) with nanometer displacement sensitivity, we investigate a novel imaging technology, optically computed phase microscopy (OCPM) that processes 3D spatial-spectral data through optical computation. We demonstrate that OCPM has the capability to image the motion of cells and magnetic nanoparticles that are mechanically excited by an external magnetic field, quantitatively and in the en face plane.

Psychological Impact of COVID-19 Epidemic on Adolescents: A Large Sample Study in China.

Background: The COVID-19 pandemic is a major public health emergency. However, little is known about the psychological impact of this pandemic on adolescents. We aim to assess the prevalence and influencing factors of depression, anxiety, and posttraumatic growth (PTG) among adolescents in a large sample study. Methods: This cross-sectional study collected demographic data and mental health measurements from 175,416 adolescents covering 31 provinces, centrally administered municipalities, and autonomous regions in mainland China from February 23 to March 8, 2020. The status of depression, anxiety, and PTG was assessed by the nine-item Patient Health Questionnaire, seven-item generalized anxiety disorder questionnaire, and post-traumatic growth inventory. Results: The prevalence of depression, anxiety, and PTG in adolescents was 35.9, 28.0, and 45.6%, respectively. The prevalence of depression and anxiety in the slight or severe epidemic areas was similar. Regression analysis showed that female sex and older age were associated with higher levels of depression, anxiety, and lower levels of PTG. Symptoms related to COVID-19, excessive attention to epidemic information, living in urban or severe epidemic areas, and conflicts with parents during home quarantine were risk factors for depression, anxiety, and PTG. Frequent communication with peers, exercise, and receiving public welfare psychological assistance were protective factors. Poor family economic status was a significant risk factor for depression and PTG. Conclusion: Our findings suggested that positive and negative psychological reactions coexist in adolescents faced with the pandemic. The factors associated with psychological problems and PTG provide strategic guidance for maintaining adolescents' mental health in China and worldwide during any pandemic such as COVID-19.