Urinary liver-type fatty acid binding protein is increased in the early stages of the disease with a risk of acute kidney injury induced by histone.

AIM: Urinary liver-type fatty acid binding protein (L-FABP) has potential utility as an early prognostic biomarker ahead of traditional severity scores in coronavirus disease 2019 and sepsis, however, the mechanism of elevated urinary L-FABP in the disease has not been clearly elucidated. We investigated the background mechanisms of urinary L-FABP excretion through non-clinical animal model focusing on histone, which is one of the aggravating factors in these infectious diseases. METHODS: Male Sprague-Dawley rats were placed in central intravenous catheters, and these rats were given a continuous intravenous infusion of 0.25 or 0.5 mg/kg/min calf thymus histones for 240 min from caudal vena cava. RESULTS: After the administration of histone, urinary L-FABP and gene expression of an oxidative stress marker in the kidney increased in a histone dose-dependent manner before increased serum creatinine. Upon further investigation, fibrin deposition in the glomerulus was observed and it tended to be remarkable in the high dose administrated groups. The levels of coagulation factor were significantly changed after the administration of histone, and these were significantly correlated with the levels of urinary L-FABP. CONCLUSIONS: Firstly, it was suggested that histone is one of the causative agents for the urinary L-FABP increase at an early stage of the disease with a risk of acute kidney injury. Secondly, urinary L-FABP could be a marker reflecting the changes of coagulation system and microthrombus caused by histone in the early stage of acute kidney injury before becoming severely ill and maybe a guide to early treatment initiation.

Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects.

SARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects (syncytium formation). We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced syncytium-forming ability. Notably, the D614G change found in globally predominant SARS-CoV-2 strains increased infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, these two features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both host proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent.IMPORTANCE The development of an effective and durable SARS-CoV-2 vaccine is essential for combating the growing COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein is the main target of neutralizing antibodies elicited during virus infection or following vaccination. Knowledge of the spike glycoprotein evolution, function and interactions with host factors will help researchers to develop effective vaccine immunogens and treatments. Here we identify key features of the spike glycoprotein, including the furin cleavage site and the D614G natural mutation, that modulate viral cytopathic effects, infectivity and sensitivity to inhibition. We also identify two inhibitors of host metalloproteases that block S-mediated cell-cell fusion, a process that contributes to the destruction of the virus-infected cell.

Potent monoclonal antibodies neutralize Omicron sublineages and other SARS-CoV-2 variants.

The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented number of mutations, raise serious concerns due to the reduced efficacy of current vaccines and resistance to therapeutic antibodies. Here, we report the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein. NA8 interacts with a highly conserved region and has a breadth of neutralization with picomolar potency against the Beta variant and the Omicron BA.1 and BA.2 sublineages and nanomolar potency against BA.2.12.1 and BA.4. Combination of NA8 and NE12 retains potent neutralizing activity against the major SARS-CoV-2 variants of concern. Cryo-EM analysis provides the structural basis for the broad and complementary neutralizing activity of these two antibodies. We confirm the in vivo protective and therapeutic efficacies of NA8 and NE12 in the hamster model. These results show that broad and potent human antibodies can overcome the continuous immune escape of evolving SARS-CoV-2 variants.

Quality of Life and Its Associated Factors Among Cancer Patients Receiving Chemotherapy at Oncology Hospitals in Vietnam After the Third Wave of the COVID-19 Pandemic.

Purpose: This study aimed to evaluate the health-related quality of life (HRQOL) of cancer patients receiving chemotherapy and identify associated factors affecting the HRQOL after the third wave of the COVID-19 pandemic in Vietnam. Patients and Methods: Patients with solid cancers receiving chemotherapy at two oncology hospitals in Vietnam during April and May 2021 were included. The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3 was used to measure the HRQOL. Three questions were asked to explore patients' concern levels about contracting COVID-19, delaying chemotherapy, or not controlling cancer well. One question was used to explore whether patients were concerned about cancer progression or COVID-19 infection more, or equally, or had no concern about both. Multiple regression models were conducted to examine factors associated with the global health status (GHS) score. Results: Of 270 included patients, mean (Standard deviation [SD]) GHS was 56.7 (20.8). Among the functional statuses, social functioning (SF) had the lowest score of 63.6 (29.2). The symptoms with the highest means were insomnia and fatigue, obtaining the score of 38.5 (31.7) and 37.3 (29.2), respectively. The mean of financial difficulties was 54.1 (32.2). In univariate analysis, high concerns about contracting COVID-19, delaying chemotherapy, not controlling cancer well, or more concern about either cancer or COVID-19 over the other were associated with worse GHS, physical functioning, emotional functioning, and SF. In multivariate analysis, those concerns and no income were significantly related to lower GHS scores besides the non-modifiable factors, such as female gender and some cancer types. Conclusion: Patients at the high concern levels, or with more concern about either cancer or COVID-19 over the other had poorer HRQOL. Interventions to address the concerns are required to improve their HRQOL, particularly for women, those without income, or with some specific cancers.

A Rotatable Paper Device Integrating Reverse Transcription Loop-Mediated Isothermal Amplification and a Food Dye for Colorimetric Detection of Infectious Pathogens.

In this study, we developed a rotatable paper device integrating loop-mediated isothermal amplification (RT-LAMP) and a novel naked-eye readout of the RT-LAMP results using a food additive, carmoisine, for infectious pathogen detection. Hydroxyl radicals created from the reaction between CuSO4 and H2O2 were used to decolor carmoisine, which is originally red. The decolorization of carmoisine can be interrupted in the presence of DNA amplicons produced by the RT-LAMP reaction due to how DNA competitively reacts with the hydroxyl radicals to maintain the red color of the solution. In the absence of the target DNA, carmoisine is decolored, owing to its reaction with hydroxyl radicals; thus, positive and negative samples can be easily differentiated based on the color change of the solution. A rotatable paper device was fabricated to integrate the RT-LAMP reaction with carmoisine-based colorimetric detection. The rotatable paper device was successfully used to detect SARS-CoV-2 and SARS-CoV within 70 min using the naked eye. Enterococcus faecium spiked in milk was detected using the rotatable paper device. The detection limits for the SARS-CoV-2 and SARS-CoV targets were both 103 copies/µL. The rotatable paper device provides a portable and low-cost tool for detecting infectious pathogens in a resource-limited environment.

Strategies That Facilitate Extraction-Free SARS-CoV-2 Nucleic Acid Amplification Tests.

The COVID-19 pandemic has resulted in an unprecedented global demand for in vitro diagnostic reagents. Supply shortages and hoarding have impacted testing capacity which has led to inefficient COVID-19 case identification and transmission control, predominantly in developing countries. Traditionally, RNA extraction is a prerequisite for conducting SARS-CoV-2 nucleic acid amplification tests (NAAT); however, simplified methods of sample processing have been successful at bypassing typical nucleic acid extraction steps, enabling extraction-free SARS-CoV-2 NAAT workflows. These methods involve chemical and physical approaches that are inexpensive and easily accessible alternatives to overcome extraction kit supply shortages, while offering acceptable test performance. Here we provide an overview of three main sample preparation strategies that have been shown to facilitate extraction-free SARS-CoV-2 NAATs.

Functional differences among the spike glycoproteins of multiple emerging severe acute respiratory syndrome coronavirus 2 variants of concern.

We compared the functional properties of spike (S) glycoproteins from the original SARS-CoV-2 strain (D614) (Wuhan, China), the globally dominant D614G strain, and emerging geographic variants: B.1.1.7 (United Kingdom), B.1.351 (South Africa), P.1 (Brazil), and B.1.1.248 (Brazil/Japan). Compared with D614G, the emerging variants exhibited an increased affinity for the receptor, ACE2, and increased ability to infect cells with low ACE2 levels. All variants lost infectivity similarly at room temperature and 37°C; however, in the cold, B.1.1.7 was more stable, and P.1 and B.1.1.248 were less stable. Shedding of the S1 glycoprotein from the S contributed to virus inactivation in the cold. B.1.351, P.1, and B.1.1.248 were neutralized by convalescent and vaccinee sera less efficiently than the other variants. S glycoprotein properties such as requirements for ACE2 levels on the target cell, functional stability in the cold, and resistance to host neutralizing antibodies potentially contribute to the outgrowth of emerging SARS-CoV-2 variants.

COVID-19-related music-video-watching among the Vietnamese population: lessons on health education.

BACKGROUND: Health education through music video plays a vital role in raising a person's knowledge, attitudes, and behaviors positively connected to health during COVID-19 pandemic. OBJECTIVE: This study aimed to estimate the prevalence of COVID-19-related music-video-watching and examine associated factors among the Vietnamese population. METHODS: A cross-sectional study in Vietnam was conducted in February 2021 via the Internet. RESULTS: Among 658 participants, the prevalence of COVID-19-related music-video-watching was 89.1% among people. In the multivariable regression models, significant factors for COVID-19-related music-video-watching were living area, types of housemate, age groups, and current occupation. CONCLUSIONS: Lessons on health education to fight against the COVID-19 pandemic in Vietnam could be useful for similar settings in the world.

Polydopamine aggregation: A novel strategy for power-free readout of loop-mediated isothermal amplification integrated into a paper device for multiplex pathogens detection.

Loop-mediated isothermal amplification (LAMP) has been widely used for detecting pathogens. However, power-free and clear visualization of results still remain challenging. In this study, we developed a paper device integrated with power-free DNA detection strategy realized by polydopamine aggregation. In the presence of DNA amplicons, the polymerization of dopamine into aggregated polydopamine was hindered, while in the absence of DNA amplicons, polydopamine aggregation is facilitated. The porosity of the paper enabled the capillary flow of dispersed polydopamine for positive sample, while aggregated polydopamine remained at the bottom of the paper strip due to large size of the aggregates for negative sample. Based on this mechanism, we fabricated a slidable paper device integrating LAMP with dopamine polymerization for the naked-eye detection, operated in a seamless manner. Moreover, the introduced paper device was successfully used to detect DNA extracted from Escherichia coli O157:H7 and SARS-CoV-2 within 25 min, as well as Enterococcus faecium within 35 min. The detection limits of both Escherichia coli O157:H7 and SARS-CoV-2 were 10-4 ng/µL. The introduced paper device can be used as a simple and sensitive tool for detecting multiple infectious pathogens, making it an ideal tool particularly for resource-limited environment.

Anxiety among the Vietnamese Population during the COVID-19 Pandemic: Implications for Social Work Practice.

The COVID-19 pandemic is a global health crisis and threatening human lives, especially vulnerable groups. This study aimed to estimate the prevalence of self-reported anxiety and to examine associated factors among the Vietnamese population during the COVID-19 pandemic. A cross-sectional study in Vietnam was conducted in April 2020. An online survey was used to do the rapid assessment. Among 1,249 participants, the prevalence of self-reported anxiety was 8.5%. In the multivariable regression models, significant factors for self-reported anxiety were people aged 60 years old or older, rural areas, and COVID-related music-video-watching. Implications for social work practice were also discussed.