6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Forecast for peak infections in the second wave of the Omicron after the adjustment of zero-COVID policy in the mainland of China.

On December 7, 2022, the Chinese government optimized the current epidemic prevention and control policy, and no longer adopted the zero-COVID policy and mandatory quarantine measures. Based on the above policy changes, this paper establishes a compartment dynamics model considering age distribution, home isolation and vaccinations. Parameter estimation was performed using improved least squares and Nelder-Mead simplex algorithms combined with modified case data. Then, using the estimated parameter values to predict a second wave of the outbreak, the peak of severe cases will reach on 8 May 2023, the number of severe cases will reach 206,000. Next, it is proposed that with the extension of the effective time of antibodies obtained after infection, the peak of severe cases in the second wave of the epidemic will be delayed, and the final scale of the disease will be reduced. When the effectiveness of antibodies is 6 months, the severe cases of the second wave will peak on July 5, 2023, the number of severe cases is 194,000. Finally, the importance of vaccination rates is demonstrated, when the vaccination rate of susceptible people under 60 years old reaches 98%, and the vaccination rate of susceptible people over 60 years old reaches 96%, the peak of severe cases in the second wave of the epidemic will be reached on 13 July 2023, when the number of severe cases is 166,000.

Safety, Pharmacokinetics, Serum Neutralizing Titers, and Immunogenicity of Adintrevimab, a Monoclonal Antibody Targeting SARS-CoV-2: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Dose-escalation Study in Healthy Adults.

INTRODUCTION: Adintrevimab is a fully human immunoglobulin G1 extended half-life monoclonal antibody that was developed to have broad neutralization against SARS-CoV, SARS-CoV-2, and other SARS-like CoVs with pandemic potential. Here we report the safety, pharmacokinetics (PK), serum viral neutralizing antibody (sVNA) titers, and immunogenicity results of the first three cohorts evaluated in the first-in-human study of adintrevimab in healthy adults. METHODS: This is a phase 1, randomized, placebo-controlled, single ascending-dose study of adintrevimab administered intramuscularly (IM) or intravenously (IV) to healthy adults aged ≥ 18-55 years with no current or prior SARS-CoV-2 infection. Participants were randomized 8:2 to adintrevimab or placebo in each of three dose cohorts: adintrevimab 300 mg IM (cohort 1), 500 mg IV (cohort 2), and 600 mg IM (cohort 3). Follow-up was 12 months. Blood samples were taken predose and at multiple time points postdose up to month 12 to assess sVNA, PK, and antidrug antibodies (ADAs). RESULTS: Thirty participants received a single dose of adintrevimab (n = 24; 8 per cohort) or placebo (n = 6). All except one adintrevimab participant in cohort 1 completed the study. No participants in any treatment arm experienced a study drug-related adverse event. Across adintrevimab-treated participants, 11 (45.8%) experienced at least one TEAE. All but one TEAE were mild in severity, and all were either viral infection or respiratory symptoms. There were no serious adverse events, discontinuations due to adverse events, or deaths. Adintrevimab exhibited a linear and dose-proportional PK profile and extended serum half-life (mean 96, 89, and 100 days in cohorts 1, 2, and 3, respectively). Participants receiving adintrevimab demonstrated dose-dependent increased sVNA titers and breadth across multiple variants. CONCLUSION: Adintrevimab at doses of 300 mg IM, 500 mg IV, and 600 mg IM was well tolerated in healthy adults. Adintrevimab demonstrated dose-proportional exposure, rapid development of neutralizing antibody titers, and an extended half-life.

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

COVID-19 infections among passengers in an inbound flight to Beijing

Objective To understand the epidemiological characteristics and laboratory test results of COVID-19 infections among passengers in an inbound flight to Beijing, and to provide reference for the management of imported COVID-19 cases. Methods Flight information, centralized quarantine sites, transfer vehicle, laboratory test results, clinical progression and outcome and other information of all passengers in an inbound flight to Beijing on August 6, 2021 were collected and analyzed. Results A total of 15 passengers were COVID-19 positive. They were all tested negative for nucleic acid 48 h before boarding. The earliest positive was on the day of entry, and the longest was on the 13th day of entry, with the median of being the 3rd day after entry. There were inconsistent nucleic acid test results of 8 positive passengers reported by two institutions and the CT values were close to cutoff. The initial serum antibody levels were higher than 100（s/co） in 6 positive passengers. Nobody was infected during transportation and quarantine. Conclusions Nucleic acid testing before boarding the flight should be able to identify majority of positive cases. Accordingly, joint screening strategy such as blood serum antibody test for inbound passengers with suspicious preliminary screening results of COVID-19 should be implemented to determine the infection history of the case.

Real-world experience of arbidol for Omicron variant of SARS-CoV-2.

Background: At a crucial time with the rapid spread of Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus variant globally, we conducted a study to evaluate the efficacy and safety of arbidol tablets in the treatment of this variant. Methods: From Mar 26 to April 26, 2022, we conducted a prospective, open-labeled, controlled, and investigator-initiated trial involving adult patients with confirmed Omicron variant infection. Patients with asymptomatic or mild clinical status were stratified 1:2 to receive either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 5 days). The primary endpoint was the negative conversion rate within the first week. Results: A total of 367 patients were enrolled in the study; 246 received arbidol tablet treatment, and 121 were in the control group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group [47.2% (116/246) vs. 35.5% (43/121); odds ratio (OR), 1.619; 95% confidence interval (CI): 1.034-2.535; P=0.035]. Compared to those in the SOC group, patients receiving arbidol tablets had a shorter negative conversion time [median 8.3 vs. 10.0 days; hazard ratio (HR), 0.645; 95% CI: 0.516-0.808; P<0.001], and a shorter duration of hospitalization (median 11.4 vs. 13.7 days; HR, 1.214; 95% CI: 0.966-1.526; P<0.001). Moreover, the addition of arbidol tablets led to better recovery of declined blood lymphocytes, CD3+, CD4+, and CD8+ cell counts. The most common adverse event (AE) was transaminase elevation in patients treated with arbidol tablets (3/246, 1.2%). No one withdrew from the study due to AEs or disease progression. Conclusions: As a whole, arbidol may represent an effective and safe treatment in asymptomatic-mild patients suffering from Omicron variant during the pandemic of coronavirus disease 2019 (COVID-19).

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques.

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

Healthy Cities, A comprehensive dataset for environmental determinants of health in England cities.

This paper presents a fine-grained and multi-sourced dataset for environmental determinants of health collected from England cities. We provide health outcomes of citizens covering physical health (COVID-19 cases, asthma medication expenditure, etc.), mental health (psychological medication expenditure), and life expectancy estimations. We present the corresponding environmental determinants from four perspectives, including basic statistics (population, area, etc.), behavioural environment (availability of tobacco, health-care services, etc.), built environment (road density, street view features, etc.), and natural environment (air quality, temperature, etc.). To reveal regional differences, we extract and integrate massive environment and health indicators from heterogeneous sources into two unified spatial scales, i.e., at the middle layer super output area (MSOA) and the city level, via big data processing and deep learning. Our data holds great promise for diverse audiences, such as public health researchers and urban designers, to further unveil the environmental determinants of health and design methodology for a healthy, sustainable city.

Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers.

Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction of multiple layers of immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure has complicated the establishment of nAbs as a mechanistic correlate of protection (CoP) and hindered the definition of a protective nAb threshold. Here, we show that a half-life-extended monoclonal antibody (adintrevimab) provides about 50% protection against symptomatic COVID-19 in SARS-CoV-2-naïve adults at serum nAb titers on the order of 1:30. Vaccine modeling results support a similar 50% protective nAb threshold, suggesting that low titers of serum nAbs protect in both passive antibody prophylaxis and vaccination settings. Extrapolation of adintrevimab pharmacokinetic data suggests that protection against susceptible variants could be maintained for about 3 years. The results provide a benchmark for the selection of next-generation vaccine candidates and support the use of broad, long-acting monoclonal antibodies as alternatives or supplements to vaccination in high-risk populations.

Immunological Findings in a Group of Individuals Who Were Poor or Non-Responders to Standard Two-Dose SARS-CoV-2 Vaccines.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic. However, data on the poor or non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of this study was to comprehensively compare the immunological characteristics of poor or non-responders to SARS-CoV-2 vaccines in the 18-59-year group with those in the ≥60-year group using internationally recognized cut-off values. The main outcome was effective seroconversion characterized by an anti-SARS-CoV-2 spike IgG level of at least a four-fold increase from baseline. Profiling of naïve immune cells was analyzed prior to vaccination to demonstrate baseline immunity. The outcomes of effective seroconversion in patients aged 18-59 years with those in patients aged ≥60 years were compared. The quantitative level of anti-spike IgG was significantly lower in individuals aged ≥60 and men aged 18-59 years. There were 7.5% of poor or non-responders among the 18-59 years and 11.7% of poor or non-responders in the ≥60 years using a four-fold increase parameter. There were 37.0-58.1% with low lymphocyte count (<1000/mm3), 33.3-45.2% with low CD4 cell counts (<500/mm3), and 74.1-96.8% with low B cell counts (<100/mm3) in the non-seroconversion group. An individual with an anti-SARS-CoV-2 spike IgG titer below 50 BAU/mL might be considered a poor or non-responder between 14 and 90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended to poor or non-responders as soon as possible to reduce disease severity and mortality.

Keep it real: Assessing destination image congruence and its impact on tourist experience evaluations

Inaccurate promotional information about tourist destinations may result in tourists' negative evaluations. This study proposes a new approach to measure the congruence between projected and received images of a destination's attractions. Based on online textual data, this study investigates how image congruence influences tourists' evaluations of their destination experiences. Using promotional messages and reviews of attractions in Hainan, China obtained from a leading Chinese online travel agency (Ctrip) and a three-way fixed-effects regression model, this study demonstrates that image congruence positively affects tourists' appraisal of their destination experiences. External crises (e.g., the COVID-19 pandemic), the readability of promotional messages, and tourists' expertise moderate this relationship, reducing the positive impact of image congruence on tourist experience evaluation. This study bridges theoretical and empirical gaps in destination image (in)congruence research, informing tourism marketing agencies of effective promotional strategies in different contexts.

Will the Construction of Sports Facilities Nudge People to Participate in Physical Exercises in China? The Moderating Role of Mental Health.

This study aims to examine the nudging effect of the sports facility construction on physical exercise (PE) participation with consideration of the moderating role of mental health in China. Multiple linear regression models are used in this study. The subjects are 4634 from the 2014 China Family Panel Studies (CFPS) data, which is a nationally representative longitudinal survey of Chinese individuals. We find that the construction of sports facilities nudges people to participate in PE, and gender, age, and education significantly influence people's participation in PE. Young, female, and better-educated people compose the "neo-vulnerable" population, who participate less in PE in China and need more interventions. Mental health status has no significant effect on people's PE participation, while it negatively moderates the nudging effect of the construction of sports facilities on PE. The results of this study suggest that only building sporting facilities is insufficient to encourage PE participation. Policies and interventions should be given to mentally disturbed individuals to guarantee and magnify the nudging effect of sports facilities on PE.

Quantitative evaluation of the role of Fangcang shelter hospitals in the control of Omicron transmission: A case study of the outbreak in Shanghai, China in 2022.

Since Omicron began to spread in China, Shanghai has become one of the cities with more severe outbreaks. Under the comprehensive consideration of the vaccine coverage rate, the number of Fangcang shelter hospital beds and the number of designated hospital beds in Shanghai, this paper established a deterministic compartmental model and used the Nelder-Mead Simplex Direct Search Algorithm and chi-square values to estimate the model parameters. we calculate ℛ0 = 3.6429 when the number of beds in the Fangcang shelter hospital is relatively tight in the second stage and ℛ0 = 0.4974 in the fifth stage when there are enough beds in both Fangcang shelter hospital and designated hospital. Then we perform a sensitivity analysis on ℛ0 by using perturbation of fixed point estimation of model parameters in the fifth stage, and obtain three parameters that are more sensitive to ℛ0, which are transmission rate (ß 1d ), proportion of the infectious (η) and the hospitalization rate of asymptomatic infected cases (δ 1). Through simulation, we obtain that if the hospitalization rate of asymptomatic infections δ 2 > 0.9373 or the transmission rate ß 1b  < 0.0467, the second stage of Omicron transmission in Shanghai can be well controlled. Finally, we find the measure that converting the National Convention and Exhibition Center (NECC) into a Fangcang shelter hospital has played an important role in curbing the epidemic. Whether this temporary Fangcang shelter hospital is not built or delayed, the cumulative number of confirmed cases will both exceed 100,000, and the cumulative asymptomatic infections will both exceed 1 million. In addition, for a city of 10 million people, we obtain that if a permanent Fangcang shelter hospital with 17,784 beds is built ahead of epidemic, there will be no shortage of beds during the outbreak of Omicron. Our findings enrich the content of the impact of Fangcang shelter hospital beds on the spread of Omicron and confirm the correct policy adopted by the Chinese government.

Data analysis guidelines for single-cell RNA-seq in biomedical studies and clinical applications.

The application of single-cell RNA sequencing (scRNA-seq) in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies. With the expansion of capacity for high-throughput scRNA-seq, including clinical samples, the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field. Here, we review the workflow for typical scRNA-seq data analysis, covering raw data processing and quality control, basic data analysis applicable for almost all scRNA-seq data sets, and advanced data analysis that should be tailored to specific scientific questions. While summarizing the current methods for each analysis step, we also provide an online repository of software and wrapped-up scripts to support the implementation. Recommendations and caveats are pointed out for some specific analysis tasks and approaches. We hope this resource will be helpful to researchers engaging with scRNA-seq, in particular for emerging clinical applications.

The conserved L1089 in the S2 subunit of avian infectious bronchitis virus determines viral kidney tropism by disrupting virus-cell fusion.

The virulence of avian gamma-coronavirus infectious bronchitis viruses (IBV) for the kidney has led to high mortality in dominant-genotype isolations, but the key sites of viral protein that determine kidney tropism are still not fully clear. In this study, the amino acid sequences of the S2 subunit of IBVs with opposing adaptivity to chicken embryonic kidney cells (CEKs) were aligned to identify putative sites associated with differences in viral adaptability. The S2 gene and the putative sites of the non-adapted CN strain were introduced into the CEKs-adapted SczyC30 strain to rescue seven mutants. Analysis of growth characteristics showed that the replacement of the entire S2 subunit and the L1089I substitution in the S2 subunit entirely abolished the proliferation of recombinant IBV in CEKs as well as in primary chicken oviduct epithelial cells. Pathogenicity assays also support the decisive role of this L1089 for viral nephrotropism, and this non-nephrotropic L1089I substitution significantly attenuates pathogenicity. Analysis of the putative cause of proliferation inhibition in CEKs suggests that the L1089I substitution affects neither virus attachment nor endocytosis, but instead fails to form double-membrane vesicles to initiate the viral replication and translation. Position 1089 of the IBV S2 subunit is conservative and predicted to lie in heptad repeat 2 domains. It is therefore reasonable to conclude that the L1089I substitution alters the nephrotropism of parent strain by affecting virus-cell fusion. These findings provide crucial insights into the adaptive mechanisms of IBV and have applications in the development of vaccines and drugs against IB.

Clinical and immune response characteristics among vaccinated persons infected with SARS-CoV-2 delta variant: a retrospective study.

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS: Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.

Single-walled carbon nanotubes-based RNA protection and extraction improves RT-qPCR sensitivity for SARS-CoV-2 detection.

The false-negative result of nucleic acid testing is an important cause of continued spread of COVID-19, while SARS-CoV-2 RNA degradation during transportation and nucleic acid extraction can lead to false-negative results. Here, we investigated that single-walled carbon nanotubes (SCNTs) could protect RNA from degradation for at least 4 days at room temperature. By constructing magnetism-functionalized SCNTs (MSCNTs), we developed a method that enabled protection and simple extraction of SARS-CoV-2 RNA, and the RNA-bound MSCNTs can be directly used for reverse transcription polymerase chain reaction (RT-qPCR) detection. The experimental results showed that 1 µg of MSCNTs adsorbed up to 24 ng of RNA. Notably, the MSCNTs-based method for extracting SARS-CoV-2 RNA from simulated nasopharyngeal swabs and saliva samples with mean recovery rates of 103% and 106% improved the sensitivity of RT-qPCR detection by 8-32 fold in comparison to current common methods. This improvement was largely attributable to the protection of RNA, enabling increased RNA load for downstream assays.

Decoy Nanozymes Enable Multitarget Blockade of Proinflammatory Cascades for the Treatment of Multi-Drug-Resistant Bacterial Sepsis.

Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection. Effective treatment of bacterial sepsis remains a paramount clinical challenge, due to its astonishingly rapid progression and the prevalence of bacterial drug resistance. Here, we present a decoy nanozyme-enabled intervention strategy for multitarget blockade of proinflammatory cascades to treat multi-drug-resistant (MDR) bacterial sepsis. The decoy nanozymes (named MCeC@MΦ) consist mesoporous silica nanoparticle cores loaded with CeO2 nanocatalyst and Ce6 photosensitizer and biomimetic shells of macrophage membrane. By acting as macrophage decoys, MCeC@MΦ allow targeted photodynamic eradication of MDR bacteria and realize simultaneous endotoxin/proinflammatory cytokine neutralization. Meanwhile, MCeC@MΦ possess intriguing superoxide dismutase and catalase-like activities as well as hydroxyl radical antioxidant capacity and enable catalytic scavenging of multiple reactive oxygen species (ROS). These unique capabilities make MCeC@MΦ to collaboratively address the issues of bacterial infection, endotoxin/proinflammatory cytokine secretion, and ROS burst, fully cutting off the path of proinflammatory cascades to reverse the progression of bacterial sepsis. In vivo experiments demonstrate that MCeC@MΦ considerably attenuate systemic hyperinflammation and rapidly rescue organ damage within 1 day to confer higher survival rates (>75%) to mice with progressive MDR Escherichia coli bacteremia. The proposed decoy nanozyme-enabled multitarget collaborative intervention strategy offers a powerful modality for bacterial sepsis management and opens up possibilities for the treatment of cytokine storm in the COVID-19 pandemic and immune-mediated inflammation diseases.

New Frontier in Antiviral Drugs for Disorders of the Respiratory System.

BACKGROUND: COVID-19 is still soaring, and the new delta COVID-19 variant is on the rise and spreading around the world. OBJECTIVE: We conducted a patent analysis to better understand the therapeutic strategy developed for antivirals available for the disorders of the respiratory system. MATERIALS AND METHODS: European granted patents filed from January 2002 to June 2021 were analyzed. We used a combination of International patent classification (IPC) "A61p31/12" and "A61p11/00" to search the relevant documents. RESULTS: Our study showed R&D of antiviral drugs for disorders of the respiratory system to be decreasing over the past 20 years. Chemical drugs showed various chemical structures. The development of chemical drugs or herbal medicines appeared to commence earlier than the biological products. Also, the results indicated that large global companies play a leading role in developing kinase inhibitors as chemical drugs. CONCLUSION: There are three strategies for developing antiviral drugs for the disorders of the respiratory system, including chemical drugs, herbal medicines or natural products, and biological products. Herbal medicines may provide a new insight and approach to developing antiviral drugs for disorders of the respiratory system. A combination of chemical drugs and natural products may be a promising therapeutic method for treating patients with COVID- 19.

Strategic COVID-19 vaccine distribution can simultaneously elevate social utility and equity.

Balancing social utility and equity in distributing limited vaccines is a critical policy concern for protecting against the prolonged COVID-19 pandemic and future health emergencies. What is the nature of the trade-off between maximizing collective welfare and minimizing disparities between more and less privileged communities? To evaluate vaccination strategies, we propose an epidemic model that explicitly accounts for both demographic and mobility differences among communities and their associations with heterogeneous COVID-19 risks, then calibrate it with large-scale data. Using this model, we find that social utility and equity can be simultaneously improved when vaccine access is prioritized for the most disadvantaged communities, which holds even when such communities manifest considerable vaccine reluctance. Nevertheless, equity among distinct demographic features may conflict; for example, low-income neighbourhoods might have fewer elder citizens. We design two behaviour-and-demography-aware indices, community risk and societal risk, which capture the risks communities face and those they impose on society from not being vaccinated, to inform the design of comprehensive vaccine distribution strategies. Our study provides a framework for uniting utility and equity-based considerations in vaccine distribution and sheds light on how to balance multiple ethical values in complex settings for epidemic control.