Gold-silver alloy hollow nanoshells-based lateral flow immunoassay for colorimetric, photothermal, and SERS tri-mode detection of SARS-CoV-2 neutralizing antibody.

Although many approaches have been developed for the quick assessment of SARS-CoV-2 infection, few of them are devoted to the detection of the neutralizing antibody, which is essential for assessing the effectiveness of vaccines. Herein, we developed a tri-mode lateral flow immunoassay (LFIA) platform based on gold-silver alloy hollow nanoshells (Au-Ag HNSs) for the sensitive and accurate quantification of neutralizing antibodies. By tuning the shell-to-core ratio, the surface plasmon resonance (SPR) absorption band of the Au-Ag HNSs is located within the near infrared (NIR) region, endowing them with an excellent photothermal effect under the irradiation of optical maser at 808 nm. Further, the Raman reporter molecule 4-mercaptobenzoic acid (MBA) was immobilized on the gold-silver alloy nanoshell to obtain an enhanced SERS signal. Thus, these Au-Ag HNSs could provide colorimetric, photothermal and SERS signals, with which, tri-mode strips for SARS-CoV-2 neutralizing antibody detection were constructed by competitive immunoassay. Since these three kinds of signals could complement one another, a more accurate detection was achieved. The tri-mode LFIA achieved a quantitative detection with detection limit of 20 ng/mL. Moreover, it also successfully detected the serum samples from 98 vaccinated volunteers with 79 positive results, exhibiting great application value in neutralizing antibody detection.

SARS-CoV-2 versus Influenza A Virus: Characteristics and Co-Treatments.

For three years, the novel coronavirus disease 2019 (COVID-19) pandemic, caused by infection of the SARS-CoV-2 virus, has completely changed our lifestyles and prepared us to live with this novel pneumonia for years to come. Given that pre-existing flu is caused by the influenza A virus, we have begun unprecedently co-coping with two different respiratory diseases at the same time. Hence, we draw a comparison between SARS-CoV-2 and influenza A virus based on the general characteristics, especially the main variants' history and the distribution of the two viruses. SARS-CoV-2 appeared to mutate more frequently and independently of locations than the influenza A virus. Furthermore, we reviewed present clinical trials on combined management against COVID-19 and influenza in order to explore better solutions against both at the same time.

Bioaccumulation Pattern of the SARS-CoV-2 Spike Proteins in Pacific Oyster Tissues.

There is mounting evidence of the contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the sewage, surface water, and even marine environment. Various studies have confirmed that bivalve mollusks can bioaccumulate SARS-CoV-2 RNA to detectable levels. However, these results do not provide sufficient evidence for the presence of infectious viral particles. To verify whether oysters can bind the viral capsid and bioaccumulate the viral particles, Pacific oysters were artificially contaminated with the recombinant SARS-CoV-2 spike protein S1 subunit (rS1). The bioaccumulation pattern of the rS1 in different tissues was investigated by immunohistological assays. The results revealed that the rS1 was bioaccumulated predominately in the digestive diverticula. The rS1 was also present in the epithelium of the nondigestive tract tissues, including the gills, mantle, and heart. In addition, three potential binding ligands, including angiotensin-converting enzyme 2 (ACE 2)-like substances, A-type histo-blood group antigen (HBGA)-like substances, and oyster heat shock protein 70 (oHSP 70), were confirmed to bind rS1 and were distributed in tissues with various patterns. The colocalization analysis of rS1 and those potential ligands indicated that the distributions of rS1 are highly consistent with those of ACE 2-like substances and oHSP 70. Both ligands are distributed predominantly in the secretory absorptive cells of the digestive diverticula and may serve as the primary ligands to bind rS1. Therefore, oysters are capable of bioaccumulating the SARS-CoV-2 capsid readily by filter-feeding behavior assisted by specific binding ligands, especially in digestive diverticula. IMPORTANCE This is the first article to investigate the SARS-CoV-2 spike protein bioaccumulation pattern and mechanism in Pacific oysters by the histochemical method. Oysters can bioaccumulate SARS-CoV-2 capsid readily by filter-feeding behavior assisted by specific binding ligands. The new possible foodborne transmission route may change the epidemic prevention strategies and reveal some outbreaks that current conventional epidemic transmission routes cannot explain. This original and interdisciplinary paper advances a mechanistic understanding of the bioaccumulation of SARS-CoV-2 in oysters inhabiting contaminated surface water.

Nervous system manifestations related to COVID-19 and their possible mechanisms.

In December 2019, the novel coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection broke. With the gradual deepening understanding of SARS-CoV-2 and COVID-19, researchers and clinicians noticed that this disease is closely related to the nervous system and has complex effects on the central nervous system (CNS) and peripheral nervous system (PNS). In this review, we summarize the effects and mechanisms of SARS-CoV-2 on the nervous system, including the pathways of invasion, direct and indirect effects, and associated neuropsychiatric diseases, to deepen our knowledge and understanding of the relationship between COVID-19 and the nervous system.

Colorimetric and Raman dual-mode lateral flow immunoassay detection of SARS-CoV-2 N protein antibody based on Ag nanoparticles with ultrathin Au shell assembled onto Fe3O4 nanoparticles.

Serological antibody tests are useful complements of nuclei acid detection for SARS-CoV-2 diagnosis, which can significantly improve diagnostic accuracy. However, antibody detection in serum or plasma remains challenging to do with high sensitivity. In this study, Ag nanoparticles with ultra-thin Au shells embedded with 4-mercaptobenzoic acid (MBA) (AgMBA@Au) were manufactured and then assembled onto Fe3O4 surface by electrostatic interaction to construct the Fe3O4-AgMBA@Au nanoparticles (NPs) with magnetic-Raman-colorimetric properties. Based on the composite nanoparticles, a colorimetric and Raman dual-mode lateral flow immunoassay (LFIA) for ultrasensitive identification of SARS-CoV-2 nucleocapsid (N) protein antibody was constructed. The magnetic nanoparticles (Fe3O4 NPs) were acted as the core and coated a layer of AgMBA@Au particles on the surface by electrostatic interaction to prepare Fe3O4-AgMBA@Au NPs, which can amplify the SERS signal due to multiple AgMBA@Au particles concentrated on a single magnetic nanoparticle. Moreover, the Fe3O4-AgMBA@Au NPs facilitated pre-purifying sample using magnetic separation, and complex matrix interference would be greatly decreased in the detection. The Fe3O4-AgMBA@Au NPs modified with N protein recognized and bound with N protein antibodies, which were trapped on the T-line, forming color band for observing detection. Under optimal conditions, the N protein antibodies could be qualitatively detected in colorimetric mode with the visual limit of 10-8 mg/mL and quantitatively detected by SERS signals between 10-6 and 10-10 mg /mL with 0.08 pg/mL detection limit. The coefficients variations (CV) of intra-assay was 8.0%, whereas of inter-assay was 11.7%, confirming of good reproducibility. Finally, this approach was able to discriminate between positive, negative, and weakly positive samples when detecting 107 clinical serum samples. The process enables highly sensitive quantitative assays that are valuable for evaluating disease processes and guiding treatment. Colorimetric and Raman dual-mode LFIA detection of SARS-CoV-2 N protein antibody based on Fe3O4-AgMBA@Au nanoparticles.

S Trimer Derived from SARS-CoV-2 B.1.351 and B.1.618 Induced Effective Immune Response against Multiple SARS-CoV-2 Variants.

The spread of SARS-CoV-2 and its variants leads to a heavy burden on healthcare and the global economy, highlighting the need for developing vaccines that induce broad immunity against coronavirus. Here, we explored the immunogenicity of monovalent or bivalent spike (S) trimer subunit vaccines derived from SARS-CoV-2 B.1.351 (S1-2P) or/and B.1. 618 (S2-2P) in Balb/c mice. Both S1-2P and S2-2P elicited anti-spike antibody responses, and alum adjuvant induced higher levels of antibodies than Addavax adjuvant. The dose responses of the vaccines on immunogenicity were evaluated in vivo. A low dose of 5 µg monovalent recombinant protein or 2.5 µg bivalent vaccine triggered high-titer antibodies that showed cross-activity to Beta, Delta, and Gamma RBD in mice. The third immunization dose could boost (1.1 to 40.6 times) high levels of cross-binding antibodies and elicit high titers of neutralizing antibodies (64 to 1024) prototype, Beta, Delta, and Omicron variants. Furthermore, the vaccines were able to provoke a Th1-biased cellular immune response. Significantly, at the same antigen dose, S1-2P immune sera induced stronger broadly neutralizing antibodies against prototype, Beta, Delta, and Omicron variants compared to that induced by S2-2P. At the same time, the low dose of bivalent vaccine containing S2-2P and S1-2P (2.5 µg for each antigen) significantly improved the cross-neutralizing antibody responses. In conclusion, our results showed that monovalent S1-2P subunit vaccine or bivalent vaccine (S1-2P and S2-2P) induced potent humoral and cellular responses against multiple SARS-CoV-2 variants and provided valuable information for the development of recombinant protein-based SARS-CoV-2 vaccines that protect against emerging SARS-CoV-2 variants.

Pearson's patterns correlational of clinical risks at admissions with hospitalization outcomes during initial COVID-19 outbreak.

COVID-19 outbreaks have crushed our healthcare systems, which requires clinical guidance for the healthcare following the outbreaks. We conducted retrospective cohort studies with Pearson's pattern-based analysis of clinical parameters of 248 hospitalized patients with COVID-19. We found that dysregulated neutrophil densities were correlated with hospitalization duration before death (p = 0.000066, r = -0.45 for % neutrophil; p = 0.0001, r = -0.47 for neutrophil count). As such, high neutrophil densities were associated with mortality (p = 4.23 × 10-31 for % neutrophil; p = 4.14 × 10-27 for neutrophil count). These findings were further illustrated by a representative "second week crash" pattern and validated by an independent cohort (p = 5.98 × 10-11 for % neutrophil; p = 1.65 × 10-7 for neutrophil count). By contrast, low aspartate aminotransferase (AST) or lactate dehydrogenase (LDH) levels were correlated with quick recovery (p ≤ 0.00005). Collectively, these correlational at-admission findings may provide healthcare guidance for patients with COVID-19 in the absence of targeted therapy.

Prevention and Control of COVID-19 after Resuming General Hospital Functions.

During the COVID-19 pandemic, many general hospitals have been transformed into designated infectious disease care facilities, where a large number of patients with COVID-19 infections have been treated and discharged. With declines in the number of hospitalizations, a major question for our healthcare systems, especially for these designated facilities, is how to safely resume hospital function after these patients have been discharged. Here, we take a designated COVID-19-care facility in Wuhan, China, as an example to share our experience in resuming hospital function while ensuring the safety of patients and medical workers. After more than 1200 patients with COVID-19 infections were discharged in late March, 2020, our hospital resumed function by setting up a three-level hospital infection management system with four grades of risk of exposure. Moreover, we also took measures to ensure the safety of medical personnel in different departments including clinics, wards, and operation rooms. After all patients with COVID-19 infections were discharged, during the five months of regular function from April to September in 2020, no positive cases have been found among more than 40,000 people in our hospital, including hospital staff and patients.

Management Strategies for COVID-19 in the General Ward of Cardiovascular Surgery: Experience From a Single Tertiary Hospital in China.

Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that threatens global health. During the pandemic period of COVID-19, the task for prevention in the general ward of cardiovascular surgery is fairly arduous. The present study intends to summarize our experience with infection control, including ward setting, admission procedures, personnel management, health education, and so on, to provide references for clinical management.

iCOVID: interpretable deep learning framework for early recovery-time prediction of COVID-19 patients.

Most prior studies focused on developing models for the severity or mortality prediction of COVID-19 patients. However, effective models for recovery-time prediction are still lacking. Here, we present a deep learning solution named iCOVID that can successfully predict the recovery-time of COVID-19 patients based on predefined treatment schemes and heterogeneous multimodal patient information collected within 48 hours after admission. Meanwhile, an interpretable mechanism termed FSR is integrated into iCOVID to reveal the features greatly affecting the prediction of each patient. Data from a total of 3008 patients were collected from three hospitals in Wuhan, China, for large-scale verification. The experiments demonstrate that iCOVID can achieve a time-dependent concordance index of 74.9% (95% CI: 73.6-76.3%) and an average day error of 4.4 days (95% CI: 4.2-4.6 days). Our study reveals that treatment schemes, age, symptoms, comorbidities, and biomarkers are highly related to recovery-time predictions.

Multidimensional Evaluation of All-Cause Mortality Risk and Survival Analysis for Hospitalized Patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19) has caused over 3.8 million deaths globally. Up to date, the number of death in 2021 is more than that in 2020 globally. Here, we aimed to compare clinical characteristics of deceased patients and recovered patients, and analyze the risk factors of death to help reduce mortality of COVID-19. Methods: In this retrospective study, a total of 2719 COVID-19 patients were enrolled, including 109 deceased patients and 2610 recovered patients. Medical records of all patients were collected between February 4, 2020, and April 7, 2020. Clinical characteristics, laboratory indices, treatments, and deep-learning system- assessed lung lesion volumes were analyzed. The effect of different medications on survival time of fatal cases was also investigated. Results: The deceased patients were older (73 years versus 60 years) and had a male predominance. Nausea (10.1% versus 4.1%) and dyspnea (54.1% versus 39.2%) were more common in deceased patients. The proportion of patients with comorbidities in deceased patients was significantly higher than those in recovered patients. The median times from hospital admission to outcome in deceased patients and recovered patients were 9 days and 13 days, respectively. Patients with severe or critical COVID-19 were more frequent in deceased group. Leukocytosis (11.35×109/L versus 5.60×109/L) and lymphocytopenia (0.52×109/L versus 1.58×109/L) were shown in patients who died. The level of prothrombin time, activated partial prothrombin time, D-dimer, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, creatine kinase, glucose, brain natriuretic peptide, and inflammatory indicators were significantly higher in deceased patients than in recovered patients. The volumes of ground-glass, consolidation, total lesions and total lung in all patients were quantified. Complications were more common in deceased patients than in recovered patients; respiratory failure (57.8%), septic shock (36.7%), and acute respiratory distress syndrome (26.6%) were the most common complications in patients who died. Many treatments were more frequent in deceased patients, such as antibiotic therapy (88.1% versus 53.7%), glucocorticoid treatment (70.6% versus 11.0%), intravenous immunoglobin treatment (36.6% versus 4.9%), invasive mechanical ventilation (62.3% versus 3.8%). Antivirals, antibiotics, traditional Chinese medicines and glucocorticoid treatment may significantly increase the survival time of fatal cases. Quantitative computed tomography imaging results were correlated with biochemical markers. Conclusions: Most patients with fatal outcomes were more likely to have common comorbidities. The leading causes of death were respiratory failure and multiple organ dysfunction syndrome. Acute respiratory distress syndrome, respiratory failure and septic shock were the most common serious complications. Antivirals, antibiotics, traditional Chinese medicines, and glucocorticoid treatment may prolong the survival time of deceased patients with COVID-19.

Problematic Internet Usage and Self-Esteem in Chinese Undergraduate Students: The Mediation Effects of Individual Affect and Relationship Satisfaction.

The aim of this cross-sectional study was to examine the mediating effects of individual affect and relationship satisfaction on the relationship between self-esteem and Problematic Internet Use (PIU). Affect was measured using the Positive and Negative Affect Schedule (PANAS), relationship satisfaction was assessed using a positive and negative semantic dimension scale, self-esteem was measured using the Rosenberg Self-Esteem Scale, and PIU was measured using the Problematic Internet Use scale with a sample of 507 Chinese university students (Mage = 20.41 years, SD = 2.49). The relationships between the variables were tested using structural equation modelling with a multiple mediation model. The results revealed that negative affect and the negative semantic dimensions of relationship satisfaction mediated the relationship between self-esteem and PIU. The implications of the results and the study's theoretical contributions are discussed.

Postpandemic Testing of Severe Acute Respiratory Syndrome Coronavirus 2 in the Huanan Seafood Market Area in Wuhan, China.

Seventy-six days after the coronavirus disease 2019 epidemic was contained in Wuhan, the Chinese government carried out a citywide severe acute respiratory syndrome coronavirus 2 nucleic acid testing initiative for all residents from 14 May to 1 June 2020. Our hospital tested 107 662 residents around Huanan seafood market, uncovering a positivity rate of 0.006%.

Severe COVID-19 in Alzheimer's disease: APOE4's fault again?

Challenges have been recognized in healthcare of patients with Alzheimer's disease (AD) in the COVID-19 pandemic, given a high infection and mortality rate of COVID-19 in these patients. This situation urges the identification of underlying risks and preferably biomarkers for evidence-based, more effective healthcare. Towards this goal, current literature review and network analysis synthesize available information on the AD-related gene APOE into four lines of mechanistic evidence. At a cellular level, the risk isoform APOE4 confers high infectivity by the underlying coronavirus SARS-CoV-2; at a genetic level, APOE4 is associated with severe COVID-19; at a pathway level, networking connects APOE with COVID-19 risk factors such as ACE2, TMPRSS2, NRP1, and LZTFL1; at a behavioral level, APOE4-associated dementia may increase the exposure to coronavirus infection which causes COVID-19. Thus, APOE4 could exert multiple actions for high infection and mortality rates of the patients, or generally, with COVID-19.

Performance of Diagnostic Model for Differentiating Between COVID-19 and Influenza: A 2-Center Retrospective Study.

BACKGROUND COVID-19 and influenza share many similarities, such as mode of transmission and clinical symptoms. Failure to distinguish the 2 diseases may increase the risk of transmission. A fast and convenient differential diagnosis between COVID-19 and influenza has significant clinical value, especially for low- and middle-income countries with a shortage of nucleic acid detection kits. We aimed to establish a diagnostic model to differentiate COVID-19 and influenza based on clinical data. MATERIAL AND METHODS A total of 493 patients were enrolled in the study, including 282 with COVID-19 and 211 with influenza. All data were collected and reviewed retrospectively. The clinical and laboratory characteristics of all patients were analyzed and compared. We then randomly divided all patients into development sets and validation sets to establish a diagnostic model using multivariate logistic regression analysis. Finally, we validated the diagnostic model using the validation set. RESULTS We preliminarily established a diagnostic model for differentiating COVID-19 from influenza that consisted of 5 variables: age, dry cough, fever, white cell count, and D-dimer. The model showed good performance for differential diagnosis. CONCLUSIONS This initial model including clinical features and laboratory indices effectively differentiated COVID-19 from influenza. Patients with a high score were at a high risk of having COVID-19, while patients with a low score were at a high risk of having influenza. This model could help clinicians quickly identify and isolate cases in the absence of nucleic acid tests, especially during the cocirculation of COVID-19 and influenza. Owing to the study's retrospective nature, further prospective study is needed to validate the accuracy of the model.

Emerging Evidence for Neuropsycho-Consequences of COVID-19.

The pandemic novel coronavirus disease (COVID-19) has become a global concern in which the respiratory system is not the only one involved. Previous researches have presented the common clinical manifestations including respiratory symptoms (i.e., fever and cough), fatigue and myalgia. However, there is limited evidence for neurological and psychological influences of SARS-CoV-2. In this review, we discuss the common neurological manifestations of COVID-19 including acute cerebrovascular disease (i.e., cerebral hemorrhage) and muscle ache. Possible viral transmission to the nervous system may occur via circulation, an upper nasal transcribrial route and/or conjunctival route. Moreover, we cannot ignore the psychological influence on the public, medical staff and confirmed patients. Dealing with public psychological barriers and performing psychological crisis intervention are an important part of public health interventions.

Mild manifestations of COVID-19 in healthcare workers.

Medical staff treating Coronavirus Disease 2019 (COVID-19) patients are at high risk for exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and many have been infected, which may cause panic among medical workers, their relatives, health professionals, and government leaders. We report the epidemiologic and clinical characteristics of healthcare workers and that the majority of infected medical staff had milder symptoms/conditions with a better prognosis than admitted patients. Timely improvement to medical staff's working conditions such as allowing adequate rest and providing sufficient medical protection is extremely important.

Radiology indispensable for tracking COVID-19.

With the rapid spread of COVID-19 worldwide, early detection and efficient isolation of suspected patients are especially important to prevent the transmission. Although nucleic acid testing of SARS-CoV-2 is still the gold standard for diagnosis, there are well-recognized early-detection problems including time-consuming in the diagnosis process, noticeable false-negative rate in the early stage and lacking nucleic acid testing kits in some areas. Therefore, effective and rational applications of imaging technologies are critical in aiding the screen and helping the diagnosis of suspected patients. Currently, chest computed tomography is recommended as the first-line imaging test for detecting COVID-19 pneumonia, which could allow not only early detection of the typical chest manifestations, but also timely estimation of the disease severity and therapeutic effects. In addition, other radiological methods including chest X-ray, magnetic resonance imaging, and positron emission computed tomography also show significant advantages in the detection of COVID-19 pneumonia. This review summarizes the applications of radiology and nuclear medicine in detecting and diagnosing COVID-19. It highlights the importance for these technologies to curb the rapid transmission during the pandemic, considering findings from special groups such as children and pregnant women.

Feasibility of Mesenchymal Stem Cell Therapy for COVID-19: A Mini Review.

Patients infected with SARS-CoV-2 carry the coronavirus disease 2019 (COVID-19) which involves multiple systems and organs with acute respiratory distress syndrome (ARDS) as the most common complication, largely due to cytokine storms or dysregulated immunity. As such, there are many severe patients with complications such as cytokine storm syndrome (CSS), who have a high fatality rate. Neither specific anti-SARS-CoV-2 drugs nor vaccines exist currently. Current treatment relies mainly on self-recovery through patients' immune function. Mesenchymal stem cells (MSCs) is a kind of multipotent tissue stem cells, which have powerful anti-inflammatory and immune regulatory functions, inhibiting the cytokine storms. In addition, MSCs have a strong ability to repair tissue damage and reduce the risk of severe complications such as acute lung injury and ARDS, and hopefully, reduce the fatality rate in these patients. There are several clinical types of research completed for treating COVID-19 with MSCs, all reporting restoration of T cells and clinical safety. Here we discuss the clinical prospect and conclude the therapeutic effects and potential mechanism for MSCs in treating COVID-19.