β-Cyclodextrin Polymer-Based Fluorescence Enhancement Strategy via Host–Guest Interaction for Sensitive Assay of SARS-CoV-2

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that β-cyclodextrin polymer (β-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host–guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host–guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3′ terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host β-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of β-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.

ß-Cyclodextrin Polymer-Based Fluorescence Enhancement Strategy via Host-Guest Interaction for Sensitive Assay of SARS-CoV-2.

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that ß-cyclodextrin polymer (ß-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host-guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host-guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3' terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host ß-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of ß-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.

Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS. This is a retrospective observational study from prospectively collected data in a cohort of 107 critically ill patients with COVID-19-induced ARDS from March 2020 to May 2021. We analyzed relationships between variables using repeated measurements correlations. We found no clinically relevant correlations between EVLW and the respiratory mechanics variables (driving pressure (correlation coefficient [CI 95%]: 0.017 [−0.064;0.098]), plateau pressure (0.123 [0.043;0.202]), respiratory system compliance (−0.003 [−0.084;0.079]) or positive end-expiratory pressure (0.203 [0.126;0.278])). Similarly, there were no relevant correlations between PVPI and these same respiratory mechanics variables (0.051 [−0.131;0.035], 0.059 [−0.022;0.140], 0.072 [−0.090;0.153] and 0.22 [0.141;0.293], respectively). In a cohort of patients with COVID-19-induced ARDS, EVLW and PVPI values are independent from respiratory system compliance and driving pressure. Optimal monitoring of these patients should combine both respiratory and TPTD variables.

Driving forces and variation in water footprint before and after the COVID-19 lockdown in Fujian Province, China

The COVID-19 outbreak has injured the global industrial supply chain, especially China as the world's largest manufacturing base. Since 2020, China has implemented a rigorous lockdown policy, which has sternly damaged sectoral trade in export-oriented coastal areas. Fujian Province, which mainly processes imported materials, has a more profound influence. Although the COVID-19 lockdown has had some detrimental consequences on the world economy, it also had some favorable benefits on the global ecology. Previous studies have shown that the lockdown has altered the physical water quantity and quality, but the lack of total, virtual, and physical water research that combines water quantity and water quality simultaneously to pinpoint the subject and responsibility of water resources consumption and pollution. This research quantified the physical, virtual, and total water consumption and water pollution among 30 sectors in Fujian Province based on the theory of water footprint and the Economic Input-Output Life Cycle Assessment model. SDA model was then used to investigate the socioeconomic elements that underpin variations in the water footprint. The results show that after the lockdown, the physical water quantity and the physical grey WF in Fujian Province decreased by 2.6 Gm3 (−6.7%) and 0.4 Gm3 (−1.3%) respectively. The virtual water quantity decreased by 2.3 Gm3 (−4.5%), whereas the virtual grey WF rose by 1.5 Gm3 (4.3%). The total water quantity dropped by 3.3 Gm3 (−4.9%), while the grey WF increased by 1.2 Gm3 (2.5%), i.e. the COVID-19 lockdown decreases physical water quantity and improves local water quality. More than 50% of the water comes from virtual water trade outside the province (virtual water is highly dependent on external), and around 60% of the grey WF comes from physical sewage in the province. The COVID-19 lockdown reduced water outsourcing across the province (paid nonlocally decrease) but increased pollution outsourcing (paid nonlocally increase). And gross capital formation's contribution to the growth in water footprint will continue to rise. As a result, this study suggested that Fujian should take advantage of sectoral trade network to enhance the transaction of green water-intensive intermediate products, reduce the physical water consumption of blue water-intensive sectors, and reduce the external dependence on water consumption. Achieving the shared responsibility of upstream and downstream water consumption and reducing the external dependence on water in water-rich regions is crucial to solving the world's water problems. This research provides empirical evidence for the long-term effects of COVID-19 lockdown on the physical and virtual water environment. Graphical abstract Image 1

Driving forces and variation in water footprint before and after the COVID-19 lockdown in Fujian Province of China.

The COVID-19 outbreak has injured the global industrial supply chain, especially China as the world's largest manufacturing base. Since 2020, China has implemented a rigorous lockdown policy, which has sternly damaged sectoral trade in export-oriented coastal areas. Fujian Province, which mainly processes imported materials, has a more profound influence. Although the COVID-19 lockdown has had some detrimental consequences on the world economy, it also had some favorable benefits on the global ecology. Previous studies have shown that the lockdown has altered the physical water quantity and quality, but the lack of total, virtual, and physical water research that combines water quantity and water quality simultaneously to pinpoint the subject and responsibility of water resources consumption and pollution. This research quantified the physical, virtual, and total water consumption and water pollution among 30 sectors in Fujian Province based on the theory of water footprint and the Economic Input-Output Life Cycle Assessment model. SDA model was then used to investigate the socioeconomic elements that underpin variations in the water footprint. The results show that after the lockdown, the physical water quantity and the physical grey WF in Fujian Province decreased by 2.6 Gm3 (-6.7%) and 0.4 Gm3 (-1.3%) respectively. The virtual water quantity decreased by 2.3 Gm3 (-4.5%), whereas the virtual grey WF rose by 1.5 Gm3 (4.3%). The total water quantity dropped by 3.3 Gm3 (-4.9%), while the grey WF increased by 1.2 Gm3 (2.5%), i.e. the COVID-19 lockdown decreases physical water quantity and improves local water quality. More than 50% of the water comes from virtual water trade outside the province (virtual water is highly dependent on external), and around 60% of the grey WF comes from physical sewage in the province. The COVID-19 lockdown reduced water outsourcing across the province (paid nonlocally decrease) but increased pollution outsourcing (paid nonlocally increase). And gross capital formation's contribution to the growth in water footprint will continue to rise. As a result, this study suggested that Fujian should take advantage of sectoral trade network to enhance the transaction of green water-intensive intermediate products, reduce the physical water consumption of blue water-intensive sectors, and reduce the external dependence on water consumption. Achieving the shared responsibility of upstream and downstream water consumption and reducing the external dependence on water in water-rich regions is crucial to solving the world's water problems. This research provides empirical evidence for the long-term effects of COVID-19 lockdown on the physical and virtual water environment.

Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS.

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS. This is a retrospective observational study from prospectively collected data in a cohort of 107 critically ill patients with COVID-19-induced ARDS from March 2020 to May 2021. We analyzed relationships between variables using repeated measurements correlations. We found no clinically relevant correlations between EVLW and the respiratory mechanics variables (driving pressure (correlation coefficient [CI 95%]: 0.017 [-0.064; 0.098]), plateau pressure (0.123 [0.043; 0.202]), respiratory system compliance (-0.003 [-0.084; 0.079]) or positive end-expiratory pressure (0.203 [0.126; 0.278])). Similarly, there were no relevant correlations between PVPI and these same respiratory mechanics variables (0.051 [-0.131; 0.035], 0.059 [-0.022; 0.140], 0.072 [-0.090; 0.153] and 0.22 [0.141; 0.293], respectively). In a cohort of patients with COVID-19-induced ARDS, EVLW and PVPI values are independent from respiratory system compliance and driving pressure. Optimal monitoring of these patients should combine both respiratory and TPTD variables.

Tidal volume challenge to predict preload responsiveness in patients with acute respiratory distress syndrome under prone position.

BACKGROUND: Prone position is frequently used in patients with acute respiratory distress syndrome (ARDS), especially during the Coronavirus disease 2019 pandemic. Our study investigated the ability of pulse pressure variation (PPV) and its changes during a tidal volume challenge (TVC) to assess preload responsiveness in ARDS patients under prone position. METHODS: This was a prospective study conducted in a 25-bed intensive care unit at a university hospital. We included patients with ARDS under prone position, ventilated with 6 mL/kg tidal volume and monitored by a transpulmonary thermodilution device. We measured PPV and its changes during a TVC (ΔPPV TVC6-8) after increasing the tidal volume from 6 to 8 mL/kg for one minute. Changes in cardiac index (CI) during a Trendelenburg maneuver (ΔCITREND) and during end-expiratory occlusion (EEO) at 8 mL/kg tidal volume (ΔCI EEO8) were recorded. Preload responsiveness was defined by both ΔCITREND ≥ 8% and ΔCI EEO8 ≥ 5%. Preload unresponsiveness was defined by both ΔCITREND < 8% and ΔCI EEO8 < 5%. RESULTS: Eighty-four sets of measurements were analyzed in 58 patients. Before prone positioning, the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen was 104 ± 27 mmHg. At the inclusion time, patients were under prone position for 11 (2-14) hours. Norepinephrine was administered in 83% of cases with a dose of 0.25 (0.15-0.42) µg/kg/min. The positive end-expiratory pressure was 14 (11-16) cmH2O. The driving pressure was 12 (10-17) cmH2O, and the respiratory system compliance was 32 (22-40) mL/cmH2O. Preload responsiveness was detected in 42 cases. An absolute change in PPV ≥ 3.5% during a TVC assessed preload responsiveness with an area under the receiver operating characteristics (AUROC) curve of 0.94 ± 0.03 (sensitivity: 98%, specificity: 86%) better than that of baseline PPV (0.85 ± 0.05; p = 0.047). In the 56 cases where baseline PPV was inconclusive (≥ 4% and < 11%), ΔPPV TVC6-8 ≥ 3.5% still enabled to reliably assess preload responsiveness (AUROC: 0.91 ± 0.05, sensitivity: 97%, specificity: 81%; p < 0.01 vs. baseline PPV). CONCLUSION: In patients with ARDS under low tidal volume ventilation during prone position, the changes in PPV during a TVC can reliably assess preload responsiveness without the need for cardiac output measurements. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04457739). Registered 30 June 2020 -Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT04457739.

Bibliometric analysis of post-traumatic stress disorder in forensic medicine: Research trends, hot spots, and prospects.

Background: Post-traumatic stress disorder (PTSD) has various risk factors, complex pathogenesis, and diverse symptoms, and is often comorbid with other injuries and diseases, making forensic diagnosis difficult. Methods: To explore the current research status and trends of PTSD, we used the Web of Science Core Collection databases to screen PTSD-related literature published between 2010 and 2021 and CiteSpace to perform bibliometric analysis. Results: In recent years, PTSD-related research has grown steadily. The countries and institutions with the most research results were the United States and England, and King's College London and Boston University, respectively. Publications were identified from 2,821 different journals, including 13 forensic-related journals, but the journal distribution was relatively scattered and there was a lack of professional core journals. Keyword co-occurrence and clustering identified many hot topics; "rat model," "mental health," and "satisfaction" were the topics most likely to have a clear effect on future research. Analysis extracted nine turning points from the literature that suggested that neural network centers, the hypothalamic-pituitary-adrenal axis, and biomarkers were new research directions. It was found that COVID-19 can cause severe psychological stress and induce PTSD, but the relationship needs further study. The literature on stress response areas and biomarkers has gradually increased over time, but specific systemic neural brain circuits and biomarkers remain to be determined. Conclusion: There is a need to expand the collection of different types of biological tissue samples from patients with different backgrounds, screen PTSD biomarkers and molecular targets using multi-omics and molecular biology techniques, and establish PTSD-related molecular networks. This may promote a systematic understanding of the abnormal activation of neural circuits in patients with PTSD and help to establish a personalized, accurate, and objective forensic diagnostic standard.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Early Humoral Responses of Hemodialysis Patients After Inactivated SARS-CoV-2 Vaccination.

Purpose: To detect antibody responses to inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis and to investigate vaccine-related adverse events. Patients and Methods: A total of 120 hemodialysis (HD) patients and 24 healthy controls (HCs) who had not been previously infected with SARS-CoV-2 and had received their first dose of the inactivated vaccine (CoronaVac; Sinovac Biotech Ltd) were recruited for this study. All participants were scheduled to receive a second dose of inactivated SARS-CoV-2 vaccine. Serum-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the SARS-CoV-2 were detected at least 14 days after the second dose of vaccine using a commercial kit. Positive and negative results were defined as a sample/cutoff (S/CO) ratio≥1.00 and <1.00, respectively. Vaccination-related adverse events were assessed using a standardized questionnaire. Results: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and the self-reported vaccination-related adverse events between HD patients and HCs. The analysis results for HD patients suggest that 82 (68.3%) and 27 (22.5%) tested positive for IgG and IgM, respectively. The levels of IgG were higher than IgM levels (P<0.0001). In addition, the IgG-positive group had significantly higher serum albumin levels than the IgG-negative group (P<0.05). Only mild vaccine-related adverse events were observed in two patients (1.66%) and in one healthy individual (4.2%). Conclusion: The seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar between HD and HCs. The inactivated SARS-CoV-2 vaccine is effective and safe in inducing near-term immunity in hemodialysis patients.

A combination vaccine against SARS-CoV-2 and H1N1 influenza based on receptor binding domain trimerized by six-helix bundle fusion core.

BACKGROUND: Increasing severe morbidity and mortality by simultaneous or sequential infections with SARS-CoV-2 and influenza A viruses (IAV), especially in the elderly and obese patients, highlight the urgency of developing a combination vaccine against COVID-19 and influenza. METHODS: Self-assembling SARS-CoV-2 RBD-trimer and Influenza H1N1 HA1-trimer antigens were constructed, upon the stable fusion core in post-fusion conformation. Immunogenicity of SARS-CoV-2 RBD-trimer vaccine and H1N1 HA1-trimer antigens candidates were evaluated in mice. Protection efficacy of a combination vaccine candidate against SARS-CoV-2 and IAV challenge was identified using the K18-hACE2 mouse model. FINDINGS: Both the resultant RBD-trimer for SARS-CoV-2 and HA1-trimer for H1N1 influenza fully exposed receptor-binding motifs (RBM) or receptor-binding site (RBS). Two-dose RBD-trimer induced significantly higher binding and neutralizing antibody titers, and also a strong Th1/Th2 balanced cellular immune response in mice. Similarly, the HA1-trimer vaccine was confirmed to exhibit potent immunogenicity in mice. A combination vaccine candidate, composed of RBD-trimer and HA1-trimer, afforded high protection efficacy in mouse models against stringent lethal SARS-CoV-2 and homogenous H1N1 influenza co-infection, characterized by 100% survival rate. INTERPRETATION: Our results represent a proof of concept for a combined vaccine candidate based on trimerized receptor binding domain against co-epidemics of COVID-19 and influenza. FUNDING: This project was funded by the Strategic Priority Research Program of CAS (XDB29040201), the National Natural Science Foundation of China (81830050, 81901680, and 32070569) and China Postdoctoral Science Foundation (2021M703450).

How Do Fresh Live Broadcast Impact Consumers' Purchase Intention? Based on the SOR Theory

During the COVID-19 pandemic, fresh live broadcasting has been widely present in consumers' daily lives but has been scarcely examined in academic research. The major purpose of the current study is to examine how fresh live broadcast features (visibility, interactivity, and authenticity) impact consumers' willingness to buy through consumers' perceived value and perceived trust based on the stimulus–organism-response theory. A total of 307 Chinese webcast users participated in this study. The data were collected through an online questionnaire survey and analyzed by SPSS and Amos software. The findings discovered that the fresh live broadcast features positively impact consumers' perceived utility value and trust, and the visibility and interactivity enhance the perceived hedonistic value of consumers. Moreover, perceived value and perceived trust mediate between fresh live broadcast features and consumers' willingness to buy. This study emphasizes the important role of fresh live features and provides insight for fresh sellers to increase consumer willingness to buy based on the perspective of consumers' perceived value and trust.

Environmental factors influencing the risk of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterized by inflammation and destruction of small and medium-sized blood vessels. Clinical disease phenotypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The incidence of AAV has been on the rise in recent years with advances in ANCA testing. The etiology and pathogenesis of AAV are multifactorial and influenced by both genetic and environmental factors, as well as innate and adaptive immune system responses. Multiple case reports have shown that sustained exposure to silica in an occupational environment resulted in a significantly increased risk of ANCA positivity. A meta-analysis involving six case-control studies showed that silica exposure was positively associated with AAV incidence. Additionally, exposure to air pollutants, such as carbon monoxide (CO), is a risk factor for AAV. AAV has seasonal trends. Studies have shown that various environmental factors stimulate the body to activate neutrophils and expose their own antigens, resulting in the release of proteases and neutrophil extracellular traps, which damage vascular endothelial cells. Additionally, the activation of complement replacement pathways may exacerbate vascular inflammation. However, the role of environmental factors in the etiology of AAV remains unclear and has received little attention. In this review, we summarized the recent literature on the study of environmental factors, such as seasons, air pollution, latitude, silica, and microbial infection, in AAV with the aim of exploring the relationship between environmental factors and AAV and possible mechanisms of action to provide a scientific basis for the prevention and treatment of AAV.

COVID-19 is associated with the risk of cardiovascular disease death: A two-sample Mendelian randomization study

Objective This study aimed to estimate the causal effects of Coronavirus disease 2019 susceptibility and hospitalization on cardiovascular disease death using two-sample Mendelian randomization analysis. Methods We used statistics from a genome-wide association study. A total of 2,568,698 participants were assessed in this study, including 1,299,010 in Coronavirus disease 2019 susceptibility databases, 908,494 in Coronavirus disease 2019 hospitalization database, and 361,194 in a cardiovascular disease death database. We performed two-sample Mendelian randomization analysis using the inverse variance weighted method. As sensitivity analysis techniques, Mendelian randomization-Egger regression, heterogeneity analyses, and Leave-one-out analysis were employed. Reverse Mendelian randomization analysis was used to detect reverse causality. Statistical significance was defined as P < 0.05. Results Coronavirus disease 2019 susceptibility may be a causal factor for cardiovascular disease death (β = 2.188 × 10–3, P = 0.002), which involves five common single nucleotide polymorphisms. Similarly, Coronavirus disease 2019 hospitalization may also be a causal factor for cardiovascular disease death (β = 8.626 × 10–4, P = 0.010), which involves nine common single nucleotide polymorphisms. Furthermore, sensitivity and reverse Mendelian randomization analysis suggested that no heterogeneity, horizontal pleiotropy or reverse causality was found between Coronavirus disease 2019 and cardiovascular disease death. Conclusion Our bidirectional Mendelian randomization analysis showed a causal relationship between Coronavirus disease 2019 susceptibility and hospitalization associated with an increased risk of cardiovascular disease death.

The Impact of Active Screening and Management on COVID-19 in Plateau Region of Sichuan, China.

Background: In December 2019, the cases of pneumonia of unknown etiology emerged in Wuhan, China, and rapidly spread throughout the country. The disease was later designated by the World Health Organization (WHO) as Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Few studies have assessed the clinical characteristics of COVID-19 and control strategies used to mitigate disease spread in high-altitude plateau regions of China. Study Objective: To assess the impact of real-world strategies to control COVID-19 spread in remote plateau regions. Methods: A retrospective study was performed to assess the epidemiology of COVID-19 and strategies used to control disease spread in the high-altitude plateau of Sichuan, China from 24 January 2020 to 19 March 2020. Results: COVID-19 spread and outbreaks in Sichuan were attributed to mass gatherings. A total of 70 patients and 20 asymptomatic individuals were found in the hypoxic plateau region of Sichuan. Twelve patients were admitted after the onset of symptoms, while 58 patients and 20 asymptomatic individuals were found by active screening. The symptomatic patients included those with uncomplicated illness (16/70, 22.9%), mild pneumonia (44/70, 62.9%), and severe pneumonia (10/70, 14.3%). Most patients in the study area showed relatively mild and atypical symptoms such as low or no fever and dyspnea. The incidence of severe pneumonia, fever, dyspnea, and interstitial abnormalities identified by chest CT were all significantly lower in screened patients than those admitted after symptom onset (P < 0.05). Severe pneumonia was noted in patients with chronic conditions like hypertension, diabetes etc. as compared to less severe pneumonia in healthy subjects (P <0.05). No patients died and all were eventually discharged. Conclusion: Mass gatherings increased risk of spread of SARS-CoV-2 responsible for COVID-19. Active screening and early management have collectively contributed to reduced incidence of severe pneumonia and satisfactory prognoses of infections with COVID-19 in this hypoxic plateau region.

[Clinical progress of neutralizing antibodies against SARS-CoV-2].

Since the palivizumab for respiratory syncytial virus was approved in 1998, therapeutic antibodies against infectious diseases have been widely used in clinical treatment. Since the outbreak of COVID-19, plenty of neutralizing antibodies were developed and transferred into clinical trials, holding enormous promise for the treatment of COVID-19 under the context of emergency use authorization. This review summarizes the clinical progress of these drugs, in order to provide a reference for the research and development of neutralizing antibody drugs for the future.

Genetic Characteristics of Porcine Hemagglutinating Encephalomyelitis Coronavirus: Identification of Naturally Occurring Mutations Between 1970 and 2015.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a Betacoronavirus characterized by neurological symptoms and a worldwide prevalence. Although PHEV is one of the earliest discovered porcine coronaviruses, it remains poorly studied. The full-length genome of the earliest PHEV strain collected in 1970 in the United States (PHEV/67 N/US/1970) was determined in October 2020. Using this virus as a prototype, we comparatively analyzed all available PHEV full-length sequences during 1970-2015. In phylogenetic trees based on PHEV full-length or spike glycoprotein open reading frame genomic sequences, PHEV/67 N/US/1970 was sorted into a clade different from that of viruses isolated in the United States in 2015. Intriguingly, United States and Belgium viruses isolated in 2015 and 2005, respectively, revealed multiple deletion mutation patterns compared to the strain PHEV/67 N/US/1970, leading to a truncated or a non-functional NS2A coding region. In addition, the genomic similarity analysis showed a hypervariability of the spike glycoprotein coding region, which can affect at least eight potential linear B cell epitopes located in the spike glycoprotein. This report indicates that PHEVs in the United States underwent a significant genetic drift, which might influence PHEV surveillance in other countries.

SARS-CoV-2 detection using quantum dot fluorescence immunochromatography combined with isothermal amplification and CRISPR/Cas13a.

The development of reliable, sensitive, and fast devices for the diagnosis of COVID-19 is of great importance in the pandemic of the new coronavirus. Here, we proposed a new principle of analysis based on a combination of reverse transcription and isothermal amplification of a fragment of the gene encoding the S protein of the SARS-CoV-2 and the CRISPR/Cas13a reaction for cleavage of the specific probe. As a result, the destroyed probe cannot be detected on an immunochromatographic strip using quantum fluorescent dots. Besides, the results can be obtained by an available and inexpensive portable device. By detecting SARS-CoV-2 negative (n = 25) and positive (n = 62) clinical samples including throat swabs, sputum and anal swabs, the assay showed good sensitivity and specificity of the method and could be completed within 1 h without complicated operation and expensive equipment. These superiorities showed its potential for fast point-of-care screening of SARS-CoV-2 during the outbreak, especially in remote and underdeveloped areas with limited equipment and resources.