Impact of the COVID-19 pandemic on emergent stroke care in Beijing, China.

The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented disruption to health care systems around the globe. Stroke is still an ongoing issue during the pandemic. We investigated the impact of the COVID-19 outbreak on emergent stroke care in Beijing, China. This is a retrospective analysis of two groups of patients with acute ischaemic stroke (AIS) registered in the Beijing Emergency Care Database between January 1, 2019, and December 31, 2020. Based on a database including 77 stroke centres, the quantity and quality of emergency care for stroke were compared. Subgroup analyses based on hospitals in different areas (high-risk and low/medium-risk areas) were carried out. A total of 6440 and 8699 admissions with suspected stroke were recorded in 2020 and 2019, respectively. There were no significant differences in the mean age and sex distribution for the patients between the two observational periods. The number of AIS admissions decreased by approximately 23.9% during the COVID-19 pandemic compared to that during the prepandemic period. The proportions of intravenous thrombolysis and endovascular treatment were 76.4% and 13.1%, respectively, in 2020, which were higher than those in 2019 (71.7% and 9.3%, respectively). There was no statistically significant difference in the time from stroke onset to arrival at the hospital (97.97 ± 23.09 min vs. 99.40 ± 20.76 min, p = 0.832) between the two periods. The door-to-needle time for thrombolysis (44.92 ± 9.20 min vs. 42.37 ± 9.06 min, p < 0.001) and door-to-thrombectomy time (138.56 ± 32.45 min vs. 120.55 ± 32.68 min, p < 0.001) were increased significantly in the pandemic period compared to those in the prepandemic period, especially in hospitals in high-risk areas. The decline in the number of patients with AIS and delay in treatment started after the launch of the level-1 public health emergency response and returned to stability after the release of professional protocols and consensus statements. Disruptions to medical services during the COVID-19 pandemic have substantially impacted AIS patients, with a clear drop in admission and a decline in the quality of emergent AIS care, especially in hospitals in high-risk areas and at the time of the initial outbreak of COVID-19. Health care systems need to maintain rapid adaptation to possible outbreaks of COVID-19 or similar crises in the future.

Comparison of common human respiratory pathogens among hospitalized children aged ≤ 6 years in Hainan Island, China, during spring and early summer in 2019-2021.

The coronavirus disease 2019 (COVID-19) pandemic and related public health intervention measures have been reported to have resulted in the reduction of infections caused by influenza viruses and other common respiratory viruses. However, the influence may be varied in areas that have different ecological, economic, and social conditions. This study investigated the changing epidemiology of 8 common respiratory pathogens, including Influenza A (IFVA), Influenza B (IFVB), Respiratory syncytial virus (HRSV), rhinovirus (RV), Human metapneumovirus Adenovirus, Human bocavirus, and Mycoplasma pneumoniae, among hospitalized children during spring and early summer in 2019-2021 in two hospitals in Hainan Island, China, in the COVID-19 pandemic era. The results revealed a significant reduction in the prevalence of IFVA and IFVB in 2020 and 2021 than in 2019, whereas the prevalence of HRSV increased, and it became the dominant viral pathogen in 2021. RV was one of the leading pathogens in the 3 year period, where no significant difference was observed. Phylogenetic analysis revealed close relationships among the circulating respiratory viruses. Large scale studies are needed to study the changing epidemiology of seasonal respiratory viruses to inform responses to future respiratory virus pandemics.

COVID-19 Infodemiology: Association Between Google Search and Vaccination in Malaysian Population.

Background In light of the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is one of the most important defensive strategies in combating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccine hesitancy or anti-vaccination attitude has become a barrier to the nationwide vaccination program, potentially sabotaging the effectiveness of vaccination. Thus far, Google Trends (GT) has been used extensively for monitoring information-seeking behavior during the pandemic. We aimed to investigate the association between Google search, the vaccination rate, and the number of vaccinated and infected cases among the Malaysian population. Material and method GT's customizable geographic and temporal filters were applied to include results for predetermined keywords from January 1, 2021, to December 31, 2021. Both Malay and English languages were used to reflect the multi-racial and multi-lingual community in Malaysia. The search volume index (SVI) derived was compared with the numbers of vaccinated and infected cases which were extracted from the open-access database (COVIDNOW in Malaysia) within the same period. Both analyses were performed independently by two authors to ensure accuracy of the data extraction process. A descriptive analysis was used to compare GT analyses and the number of daily vaccinations and positive COVID-19 cases. Results The information-seeking behavior in the public fluctuated from time to time. The interest surged during the initiation of vaccination program and upon the outbreak of COVID-19 in Malaysia. The surge in interest prior to the peak of vaccination rate also indicated that the public tended to get information online prior to getting the vaccines.  Conclusion This observational study illustrates the ability of GT to monitor the interest of vaccination among the Malaysian population during the pandemic. By monitoring the dynamic changes in Google Trends, healthcare authorities can get a glimpse of public perceptions such as attitude towards COVID-19 vaccine, hence potentially identify and stymie any dangerous online anti-vaccination rhetoric swiftly.

Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events.

The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, 18 core mutations of BA.1 (frequency >99%) and 27 core mutations of BA.2 (nine more than BA.1) were identified, of which 15 are specific to Omicron. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations in BA.1 than BA.2, and BA.1 is phylogenetically closer to Alpha than other variants. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1. Most notably, multiple characteristic amino acid mutations in the Delta spike protein have been also identified in the "Deltacron"-like Omicron Variants isolated since November 11, 2021 in South Africa, which implies the recombination events occurring between the Omicron and Delta variants. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.

Epidemiology and Comparative Analyses of the S Gene on Feline Coronavirus in Central China.

Feline coronavirus (FCoV) infections present as one of two forms: a mild or symptom-less enteric infection (FEC) and a fatal systemic disease termed feline infectious peritonitis (FIP). The lack of epidemiology of FCoV in central China and the reason why different symptoms are caused by viruses of the same serotype have motivated this investigation. Clinical data of 81 suspected FIP cases, 116 diarrhea cases and 174 healthy cases were collected from veterinary hospitals using body cavity effusion or fecal samples. Risk factors, sequence comparison and phylogenetic studies were performed. The results indicated that FIPV was distinguished from FECV in the average hydrophobicity of amino acids among the cleavage sites of furin, as well as the mutation sites 23,531 and 23,537. FIPV included a higher minimal R-X-X-R recognition motif of furin (41.94%) than did FECV (9.1%). The serotype of FCoV was insignificantly correlated with FIP, and the clade 1 and clade 2 strains that appeared were unique to central China. Thus, it is hypothesized that this, along with the latent variables of an antigenic epitope at positions 1058 and 1060, as well as mutations at the S1/S2 sites, are important factors affecting FCoV transmission and pathogenicity.

Ruxolitinib attenuates secondary injury after traumatic spinal cord injury.

Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were treated with RUX for 24 hours and then activated with interferon-γ for 6 hours. The results showed that interferon-γ-induced phosphorylation of JAK and STAT in microglia was inhibited, and the mRNA expression levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1ß, interleukin-6, and cell proliferation marker Ki67 were reduced. In further in vivo experiments, a mouse model of spinal cord injury was treated intragastrically with RUX for 3 successive days, and the findings suggest that RUX can inhibit microglial proliferation by inhibiting the interferon-γ/JAK/STAT pathway. Moreover, microglia treated with RUX centripetally migrated toward injured foci, remaining limited and compacted within the glial scar, which resulted in axon preservation and less demyelination. Moreover, the protein expression levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were reduced. The neuromotor function of SCI mice also recovered. These findings suggest that RUX can inhibit neuroinflammation through inhibiting the interferon-γ/JAK/STAT pathway, thereby reducing secondary injury after SCI and producing neuroprotective effects.

COVID-19 Collateral Damage: Management of Periprosthetic Joint Infection in Malaysia

Background and objective Periprosthetic joint infection (PJI) is one of the dreaded complications in patients after arthroplasty surgeries, owing to the risk of morbidity and arduous investigations and management associated with it. Nevertheless, as Malaysia is currently battling against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic head-on, the treatment for other non-life-threatening diseases including PJI has taken a backseat. In this study, we present a case series of 11 patients with PJI who were managed surgically at the largest tertiary hospital in Malaysia and we hope to shed some light on the difficulties we have encountered during this trying period. Patients and methods Patients with PJIs who underwent surgical intervention during the ongoing COVID-19 pandemic (March 1, 2020, to June 30, 2021) were reviewed and included in this study. The demographic profile of the patients, presenting complaints, prosthesis topography, biochemical investigative findings, surgical interventions, and short-term outcomes were summarized. Results A total of 11 patients were treated surgically at Hospital Kuala Lumpur for PJI. Among them, five patients are still awaiting their second-stage surgeries despite the completion of their antibiotic regimes, and they are fit for the procedure. Conclusion The COVID-19 pandemic has wreaked havoc on the treatment of patients with PJI. In a setting with scarce resources, surgeons should strongly consider single-stage revision surgeries for the treatment of patients with PJI.

V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity.

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.

Negative and positive psychological experience of frontline nurses in combatting COVID-19: A qualitative study.

AIMS: To qualitatively explore potential experience among frontline nurses who had been fighting against the COVID-19 infection since the outbreak. BACKGROUND: Disasters are often sudden and uncertain. Since the COVID-19 outbreak in Wuhan city, local frontline nurses had been responsible for treatment of COVID-19 for several months. Qualitative study was required to assess complex multi-component psychological experiences among frontline nurses. METHODS: Twenty local frontline nurses were recruited from a designated hospital of COVID-19 treatment. We conducted semi-structured interview using phenomenological method. Descriptive phenomenological method was applied for thematic analysis. RESULTS: Twenty female frontline nurses (aged 24 to 43 years old) were interviewed. Two broader themes, negative and positive, were identified. Negative experience included refusal and helpless (refusal to work at frontline, shortage of confidence in working and helpless), fear and anxiety, excessive miss, and other health issues. Positive experience included improved interpersonal relationship, sublimation of personal faith and strength, changes in understanding meaning of life and new possibility. CONCLUSION: Both positive and negative psychological response were observed, which can provide evidence based clues for making essential strategies and policy. IMPLICATIONS FOR NURSING MANAGEMENT: Understand subjective experience of frontline nurses can establish evidence for development of effective psychological intervention. Nursing administrator should consider the nurses' psychological experience comprehensively to promote psychological growth and lower post-traumatic psychological burden.

Air quality, COVID-19, and the oil market: Evidence from China’s provinces

This study examined the relationship between the air quality index (AQI), COVID-19, and the oil market using China’s provincial data for the first four months of the pandemic (1 January – 22 April 2020). The results show that air quality improved significantly during this period. Our income and regional group analyses further clarified that the middle-income group and Eastern and Central provinces, which were most affected by COVID-19, showed a more robust relationship between AQI and COVID-19 cases than other Chinese provinces. The national oil market, which saw a 57% decline in the oil price over the period of 13 January to 22 April, was also found to be insignificantly related to AQI. All in all, our paper implies that an improvement in air quality due to a drastic decline in economic activity. We provide some future research directions in the paper.

Immune response induced by oral administration with a Saccharomyces cerevisiae-based SARS-CoV-2 vaccine in mice.

BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic. RESULTS: We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model. CONCLUSIONS: Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.

Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression.

The ongoing unprecedented severe acute respiratory syndrome caused by the SARS-CoV-2 outbreak worldwide has highlighted the need for understanding viral-host interactions involved in mechanisms of virulence. Here, we show that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, which is responsible for nuclear export of cellular mRNAs. Nsp1 prevents proper binding of NXF1 to mRNA export adaptors and NXF1 docking at the nuclear pore complex. As a result, a significant number of cellular mRNAs are retained in the nucleus during infection. Increased levels of NXF1 rescues the Nsp1-mediated mRNA export block and inhibits SARS-CoV-2 infection. Thus, antagonizing the Nsp1 inhibitory function on mRNA export may represent a strategy to restoring proper antiviral host gene expression in infected cells.

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The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major outbreak in the world. SARS-CoV-2 infection can not only involve in the respiratory system, but also cause severe nervous system damage. Studies have shown that SRAS-CoV-2 can invade the nervous system through hematogenous and transneuronal pathways, and may cause nervous system damage in patients with COVID-19 by inhibiting cellular immunity, hypoxemia, inflammation, inducing neuronal degeneration and apoptosis, and angiotensin converting enzyme 2 (ACE2) mechanism. It can lead to intracranial infection, toxic encephalopathy, acute cerebrovascular disease, muscle damage, peripheral nervous system injury, acute myelitis, demyelination disease or other nervous system diseases.

SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.

Treatment with convalescent plasma for COVID-19 patients in Wuhan, China.

The discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outbreak of coronavirus disease 2019 (COVID-19) are causing public health emergencies. A handful pieces of literature have summarized its clinical and radiologic features, whereas therapies for COVID-19 are rather limited. To evaluate the efficacy of convalescent plasma therapy in COVID-19 patients, we did this timely descriptive study. Six laboratory-confirmed COVID-19 patients were enrolled and received the transfusion of ABO-compatible convalescent plasma. The efficacy of this intervention was determined by the alleviation of symptoms, changes in radiologic abnormalities and laboratory tests. No obvious adverse effect observed during the treatment. Transfusion of convalescent plasma led to a resolution of ground-glass opacities and consolidation in patients #1, #2, #3, #4, and #6. In patients #1 and #5 who presented with SARS-CoV-2 in throat swab, convalescent plasma therapy elicited an elimination of the virus. Serologic analysis indicated an immediate increase in anti-SARS-CoV-2 antibody titers in patients #2 and #3, but not in patient #1. This study indicates that convalescent plasma therapy is effective and specific for COVID-19. This intervention has a special significance for eliminating SARS-CoV-2 and is believed to be a promising state-of-the-art therapy during COVID-19 pandemic crisis.