Linear spot Raman detector for the bi-channel immunochromatographic assay to simultaneously detect respiratory viruses

The rapid and accurate measurement of Raman signals on the test line (T-line) of surface-enhanced Raman scattering immunochromatography assay (SERS-ICA) strip is necessary for on-site detection based on SERS. Here, a novel linear spot Raman detector which can directly collect the SERS signals of the whole T-line on the dual-diagnostic SERS-ICA strip is developed for detection of multiple respiratory viruses via two magnetic SERS tags within 26min. The tags modified with two Raman reporter molecules can specifically recognize two viruses, thus enabling the simultaneous detection of both viruses on one T-line. Measured by the linear Raman detector, the limits of detection of the proposed dual-diagnostic SERS-ICA strip is as low as 870 and 263 copies/mL for severe acute respiratory syndrome coronavirus 2 and H1N1, respectively. The dual-diagnostic strip combined with the novel Raman detector herein are of great importance in the differential diagnosis of respiratory pathogens and show potential in the rapid and accurate diagnosis and control of emerging acute respiratory diseases.

Efficacy of Early Inpatient Rehabilitation of Post COVID 19 Survivors-Single Center Retrospective Analysis.

OBJECTIVE: To understand the demographic, clinical characteristics and effectiveness of early inpatient rehabilitation of post COVID survivors. DESIGN: Single center retrospective chart review analysis of 100 patients admitted to newly created acute COVID rehab unit (CORE+) from April to December 2020. RESULTS: The demographic, clinical characteristics and complications of 100 post COVID patients were reviewed. Functional outcomes of GG self-care and mobility items of IRF-PAI (Version 3.0) at admission and discharge, prevalence of the oxygen requirement, the need of cognitive and neuropsychology support by discharge and the dispositions after completion of IRF were analyzed. The functional outcomes of 59 primary pulmonary manifestation of COVID patients were further analyzed based on presence of ICU stay prior to transfer to COVID Rehab unit. The majority of patients demonstrated significant functional gains after completion of IRF, however, a considerable number of patients continued to require cognitive support by discharge. CONCLUSION: The data suggested the benefit of early rehabilitation for hospitalized post COVID patients. Services need to be geared to include patients' cognitive deficits.

Simultaneously ultrasensitive and quantitative detection of influenza A virus, SARS-CoV-2, and respiratory syncytial virus via multichannel magnetic SERS-based lateral flow immunoassay.

Respiratory viruses usually induced similar clinical symptoms at early infection. Herein, we presented a multichannel surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFA) using high-performance magnetic SERS tags for the simultaneous ultrasensitive detection of respiratory viruses, namely influenza A virus (H1N1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) in biological samples. As-prepared magnetic SERS tags can directly enrich and capture target viruses without pretreatment of samples, avoiding the interference of impurities in the samples as well as improving the sensitivity. With the capture-detection method, the detection limits of the proposed assay reached 85 copies mL-1, 8 pg mL-1, and 8 pg mL-1 for H1N1, SARS-CoV-2 and RSV, respectively. Moreover, the detection properties of the proposed method for target viruses in throat swab samples were verified, suggesting its remarkable potential for the early and rapid differential diagnosis of respiratory viruses.

[Research Progress on Reproductive System Damage in Male Coronavirus Disease 2019 Patients].

The incidence and severity of coronavirus disease 2019(COVID-19) have significant gender differences.Males are more likely to contract severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) than the age-matched females.The virus uses angiotensin-converting enzyme 2(ACE2) receptors to enter human cells.In addition to infecting the respiratory system,ACE2 can also attack the digestive system,nervous system,immune system and so on,due to the various levels of expression in multiple human organs.The testes are one of the ACE2-rich organs.SARS-CoV-2 has been detected in the semen of some COVID-19 patients,which suggests that SARS-CoV-2 may damage the male reproductive system.However,the damage mechanism remains to be studied.The available studies focus on the short-term effect of SARS-CoV-2 on male reproduction and increasing attention has been paid to the long-term effect.This paper briefly describes the possible mechanisms of reproductive cell damage,hypogonadism,and testicular inflammation mediated by SARS-CoV-2 in male COVID-19 patients and points out the existing problems in the current studies,which will broaden the thinking for deciphering the mechanism of reproductive system damage in male COVID-19 patients.

A Community-Based Participatory Research Approach to Developing and Testing Social and Behavioural Interventions to Reduce the Spread of SARS-CoV-2: A Protocol for the 'COPAR for COVID' Programme of Research with Five Interconnected Studies in the Hong Kong Context.

BACKGROUND: While a number of population preventive measures for COVID-19 exist that help to decrease the spread of the virus in the community, there are still many areas in preventative efforts that need improvement or refinement, particularly as new strains of the virus develop. Some of the key issues currently include incorrect and/or inconsistent use of face masks, low acceptance of early screening or vaccination for COVID-19, vaccine hesitance, and misinformation. This is particularly the case in some vulnerable populations, such as older people with chronic illnesses, ethnic minorities who may not speak the mainstream language well and children. The current protocol introduces a large programme of research through five interrelated studies that all focus on social and behavioural interventions to improve different aspects of community-related preventative indicators. Hence, the specific objectives of the overall programme are to (1) increase early testing for COVID-19 and promote the uptake of COVID-19 vaccines in the community (Study 1); (2) increase COVID-19-related health literacy and vaccine literacy and promote improved preventative measures in minority ethnic groups, chronically ill populations and caregivers (Study 2); (3) strengthen the public's motivation to stay at home and avoid nonessential high-risk activities (Study 3); (4) decrease COVID-19 vaccine hesitancy (Study 4); and (5) enhance the adherence to COVID-19-related hygiene practices and the uptake of early testing in school children (Study 5). METHODS: We will utilise a community-based participatory research (CBPR) approach in the proposed studies. All studies will incorporate an intervention development phase in conjunction with key community stakeholders, a feasibility study and an execution stage. A variety of self-reported and objective-based measures will be used to assess various outcomes, based on the focus of each study, in both the short- and long-term, including, for example, the 8-item self-reported eHealth Literacy Scale (eHEAL) and objective measures such as vaccine uptake. DISCUSSION: Theory-driven interventions will address each study's focus (e.g., social distancing, promotion of vaccine uptake, eHealth education, preventive measures and early detection). Improvements are expected to be seen in the outcomes of vulnerable and high-risk groups. Decreased infection rates are expected due to improved preventative behaviours and increased vaccine uptake. Long-term sustainability of the approach will be achieved through the CBPR model. The publication of this protocol can assist not only in sharing a large-scale and complex community-based design, but will also allow all to learn from this, so that we will have better insight in the future whether sharing of study designs can elicit timely research initiatives.

The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Rapid field determination of SARS-CoV-2 by a colorimetric and fluorescent dual-functional lateral flow immunoassay biosensor.

The rapid and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the early stage of virus infection can effectively prevent the spread of the virus and control the epidemic. Here, a colorimetric and fluorescent dual-functional lateral flow immunoassay (LFIA) biosensor was developed for the rapid and sensitive detection of spike 1 (S1) protein of SARS-CoV-2. A novel dual-functional immune label was fabricated by coating a single-layer shell formed by mixing 20 nm Au nanoparticles (Au NPs) and quantum dots (QDs) on SiO2 core to produce strong colorimetric and fluorescence signals and ensure good monodispersity and high stability. The colorimetric signal was used for visual detection and rapid screening of suspected SARS-CoV-2 infection on sites. The fluorescence signal was utilized for sensitive and quantitative detection of virus infection at the early stage. The detection limits of detecting S1 protein via colorimetric and fluorescence functions of the biosensor were 1 and 0.033 ng/mL, respectively. Furthermore, we evaluated the performance of the biosensor for analyzing real samples. The novel biosensor developed herein had good repeatability, specificity and accuracy, which showed great potential as a tool for rapidly detecting SARS-CoV-2.

Development of an ultrasensitive fluorescent immunochromatographic assay based on multilayer quantum dot nanobead for simultaneous detection of SARS-CoV-2 antigen and influenza A virus.

Rapid and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FluA) antigens in the early stages of virus infection is the key to control the epidemic spread. Here, we developed a two-channel fluorescent immunochromatographic assay (ICA) for ultrasensitive and simultaneous qualification of the two viruses in biological samples. A high-performance quantum dot nanobead (QB) was fabricated by adsorption of multilayers of dense quantum dots (QDs) onto the SiO2 surface and used as the highly luminescent label of the ICA system to ensure the high-sensitivity and stability of the assay. The combination of monodispersed SiO2 core (∼180 nm) and numerous carboxylated QDs formed a hierarchical shell, which ensured that the QBs possessed excellent stability, superior fluorescence signal, and convenient surface functionalization. The developed ICA biosensor achieved simultaneous detection of SARS-CoV-2 and FluA in one test within 15 min, with detection limits reaching 5 pg/mL for SARS-CoV-2 antigen and 50 pfu/mL for FluA H1N1. Moreover, our method showed high accuracy and specificity in throat swab samples with two orders of magnitude improvement in sensitivity compared with traditional AuNP-based ICA method. Hence, the proposed method is a promising and convenient tool for detection of respiratory viruses.

Watch out for neuromyelitis optica spectrum disorder after inactivated virus vaccination for COVID-19.

With recent availability of COVID-19 vaccine, post-vaccination neurological complications had been occasionally reported. Here, we reported for the first time a case of neuromyelitis optica spectrum disorder (NMOSD) that developed after the first dose of inactivated virus vaccine for COVID-19. The patient developed mild fever, vomiting, diarrhea, and cough after receiving the first dose of inactivated virus vaccine. Two months later, she experienced dizziness and unsteady walking. MRI scanning of the brain revealed lesions in area postrema and bilateral hypothalamus, typical for NMOSD. Serum antibodies for AQP4, ANA, SSA, SSB, Ro-52, and p-ANCA were positive. The patient was diagnosed as AQP4-positive NMOSD with coexisting systemic autoimmunity. After treatment with methylprednisolone (500 mg for 5 days), symptoms were greatly relieved. As NMOSD is seriously harmful and curative, it is important to be aware of the NMOSD symptoms after vaccination. Cautions should be given for those with preexisting systemic autoimmune abnormalities in vaccination for COVID-19.

Innovations in Geroscience to enhance mobility in older adults.

Aging is the primary risk factor for functional decline; thus, understanding and preventing disability among older adults has emerged as an important public health challenge of the 21st century. The science of gerontology - or geroscience - has the practical purpose of "adding life to the years." The overall goal of geroscience is to increase healthspan, which refers to extending the portion of the lifespan in which the individual experiences enjoyment, satisfaction, and wellness. An important facet of this goal is preserving mobility, defined as the ability to move independently. Despite this clear purpose, this has proven to be a challenging endeavor as mobility and function in later life are influenced by a complex interaction of factors across multiple domains. Moreover, findings over the past decade have highlighted the complexity of walking and how targeting multiple systems, including the brain and sensory organs, as well as the environment in which a person lives, can have a dramatic effect on an older person's mobility and function. For these reasons, behavioral interventions that incorporate complex walking tasks and other activities of daily living appear to be especially helpful for improving mobility function. Other pharmaceutical interventions, such as oxytocin, and complementary and alternative interventions, such as massage therapy, may enhance physical function both through direct effects on biological mechanisms related to mobility, as well as indirectly through modulation of cognitive and socioemotional processes. Thus, the purpose of the present review is to describe evolving interventional approaches to enhance mobility and maintain healthspan in the growing population of older adults in the United States and countries throughout the world. Such interventions are likely to be greatly assisted by technological advances and the widespread adoption of virtual communications during and after the COVID-19 era.

Development of a SERS-based lateral flow immunoassay for rapid and ultra-sensitive detection of anti-SARS-CoV-2 IgM/IgG in clinical samples.

The accurate and rapid screening of serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the key to control the spread of 2019 coronavirus disease (COVID-19). In this study, we reported a surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-LFIA) for the simultaneous detection of anti-SARS-CoV-2 IgM/IgG with high sensitivity. Novel SERS tags labeled with dual layers of Raman dye were fabricated by coating a complete Ag shell on SiO2 core (SiO2@Ag) and exhibited excellent SERS signals, good monodispersity, and high stability. Anti-human IgM and IgG were immobilized onto the two test lines of the strip to capture the formed SiO2@Ag-spike (S) protein-anti-SARS-CoV-2 IgM/IgG immunocomplexes. The SERS signal intensities of the IgM and IgG test zones were easily recorded by a portable Raman instrument and used for the high-sensitivity analysis of target IgM and IgG. The limit of detection of SERS-LFIA was 800 times higher than that of standard Au nanoparticle-based LFIA for target IgM and IgG. The SERS-LFIA biosensor was tested on 19 positive serum samples from COVID-19 patients and 49 negative serum samples from healthy people to demonstrate the clinical feasibility of our proposed assay. The results revealed that the proposed method exhibited high accuracy and specificity for patients with SARS-CoV-2 infection.

The Important Role of Volatile Components From a Traditional Chinese Medicine Dayuan-Yin Against the COVID-19 Pandemic.

Aromatic Chinese herbs have been used to prevent plagues since ancient times. Traditional Chinese medicine has unique advantages in the prevention and treatment of epidemic diseases. According to the traditional Chinese medicine treatment plan in the National COVID-19 Diagnosis and Treatment Plan (Trial Seventh Edition) of the National Health Commission, Chinese patent medicines or prescriptions rich in aromatic Chinese herbs are selected for prevention and treatment during the period of medical observation, clinical treatment, and recovery of confirmed COVID-19 patients. Some local health committees or traditional Chinese medicine administrations recommend a variety of other ways of using traditional aromatic Chinese herbs to prevent and cure COVID-19. These involve external fumigation, use of moxibustion, and wearing of sachet. The efficacy of aromatic Chinese herbs plays a decisive role in the prevention and treatment of COVID-19. The unique properties, chemical composition, and mechanism of action of aromatic Chinese herbs are worthy of extensive and in-depth experimental and clinical research. The findings are expected to provide a reference for follow-up treatment of novel coronavirus and the development of corresponding drugs. In 2003, Dayuan-Yin produced excellent results in the treatment of the SARS virus. Individually, 112 confirmed cases were administered this drug between January and April 2003, and more than 93.7% of the patients showed noticeable mitigation of the symptoms, as well as recovery. Dayuan-Yin also was selected as one of the nationally recommended prescriptions for the COVID-19. Based on the national recommendation of Dayuan-Yin prescription, this review discusses the role of volatile components in the prevention and treatment of COVID-19, and speculates the possible mechanism of action, so as to provide a basis for the prevention and treatment of COVID-19.