Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBPCorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% versus 6.8%), and no relapse occurred within one month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 were rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

Differences in mental health and alcohol use across profiles of COVID-19 disruptions.

This study aimed to examine differences in mental health and alcohol use outcomes across distinct patterns of work, home, and social life disruptions associated with the COVID-19 pandemic. Data from 2093 adult participants were collected from September 2020 to April 2021 as a part of a larger study examining the impacts of the COVID-19 pandemic on substance use. Participants provided data on COVID-19 pandemic experiences, mental health outcomes, media consumption, and alcohol use at baseline. Alcohol use difficulties, including problems related to the use, desire to use alcohol, failure to cut down on alcohol use, and family/friend concern with alcohol use, were measured at 60-day follow-up. Factor mixture modeling followed by group comparisons, multiple linear regressions, and multiple logistic regressions was conducted. A four-profile model was selected. Results indicated that profile membership predicted differences in mental health and alcohol use outcomes above and beyond demographics. Individuals experiencing the most disruption reported the strongest daily impact of COVID-19 and significantly high levels of depression, anxiety, loneliness, overwhelm, alcohol use at baseline, and alcohol use difficulties measured at 60-day follow-up. The findings highlight the need for integrated mental health and/or alcohol services and social services targeting work, home, and social life during public health emergencies in order to respond effectively and comprehensively to the needs of those requiring different types of support.

Model analysis of smart supply chain finance of platform-based enterprises under government supervision

The COVID-19 pandemic has made it more difficult and expensive for medium-sized enterprises (SMEs) to finance. In this context, relying on the network platform, smart supply chain finance effectively solves financing problems for small and SMEs. However, in the development of smart supply chain finance, there are still some problems such as unstable willingness of SMEs to participate in financing, difficulty in determining the optimal development mode of platform-based core enterprises and lack of appropriate regulatory measures. Based on whether the network platform can use its own capitals for lending, this study introduces two smart supply chain financial models (the dominant and cooperation models of platform-based core enterprises) to solve the above problems. In this study, we construct two evolutionary game models: the tripartite model, including government, platform-based core enterprises, and SMEs, and the quadrilateral model, including government, financial institutions, platform-based core enterprises, and SMEs. This study presents the evolution and stability strategies of each participant under different modes. In addition, we discuss the willingness of platforms to choose different modes and corresponding government supervision measures. This study offers several important conclusions. (1) Core enterprises that do not have the conditions to build a highly intelligent platform choose the cooperation model;otherwise, they will preferentially choose the dominant mode. (2) Under the dominant mode, the stable development of smart supply chain finance must rely on strict government supervision. (3) By adjusting the scope of tax rates and subsidies, the government can control the trend of mutual transformation of the two modes, so that the dominant mode and the cooperative mode can develop in a balanced way in the market.

Model analysis of smart supply chain finance of platform-based enterprises under government supervision.

The COVID-19 pandemic has made it more difficult and expensive for medium-sized enterprises (SMEs) to finance. In this context, relying on the network platform, smart supply chain finance effectively solves financing problems for small and SMEs. However, in the development of smart supply chain finance, there are still some problems such as unstable willingness of SMEs to participate in financing, difficulty in determining the optimal development mode of platform-based core enterprises and lack of appropriate regulatory measures. Based on whether the network platform can use its own capitals for lending, this study introduces two smart supply chain financial models (the dominant and cooperation models of platform-based core enterprises) to solve the above problems. In this study, we construct two evolutionary game models: the tripartite model, including government, platform-based core enterprises, and SMEs, and the quadrilateral model, including government, financial institutions, platform-based core enterprises, and SMEs. This study presents the evolution and stability strategies of each participant under different modes. In addition, we discuss the willingness of platforms to choose different modes and corresponding government supervision measures. This study offers several important conclusions. (1) Core enterprises that do not have the conditions to build a highly intelligent platform choose the cooperation model; otherwise, they will preferentially choose the dominant mode. (2) Under the dominant mode, the stable development of smart supply chain finance must rely on strict government supervision. (3) By adjusting the scope of tax rates and subsidies, the government can control the trend of mutual transformation of the two modes, so that the dominant mode and the cooperative mode can develop in a balanced way in the market.

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19.

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.

COVID-19 vaccine affects neither prothrombotic antibody profile nor thrombosis in primary antiphospholipid syndrome: a prospective study.

OBJECTIVE: To explore whether inactivated COVID-19 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary antiphospholipid syndrome (APS) patients. METHODS: We enrolled 39 primary APS patients who received two doses of inactivated SARS-CoV-2 vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and four weeks after the 2nd dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. RESULTS: There was no significant difference in the presence of all eleven autoantibodies detected before and four weeks after vaccination: for aCL, IgG (14 vs. 16, P= 0.64), IgM (13 vs. 19, P= 0.34), IgA (2 vs. 3, P= 0.64); anti-ß2GP1, IgG (12 vs. 12, P= 1.00), IgM (5 vs. 8, P= 0.36), IgA (4 vs. 3, P= 0.69); aPS/PT IgG (13 vs. 16, P= 0.48), IgM (17 vs. 22, P= 0.26); LAC (22 vs. 28, P= 0.16); aPF4-heparin (0 vs. 0, P= 1.00), and antinuclear antibody (ANA) (23 vs. 26, P= 0.48). Notably, the distribution of aPL profile in pre- and post- vaccination cohort was not affected by SARS-CoV-2 vaccination: for patients with low-risk aPL profile (11 vs. 10, P= 0.799) and patients with high-risk aPL profile (28 vs. 29, P= 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. CONCLUSIONS: Inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients.

COVID-related social determinants of substance use disorder among diverse U.S. racial ethnic groups.

OBJECTIVE: Black, Asian, and Hispanic/Latino people are disproportionately impacted by the COVID-19 pandemic and were more likely to experience coronavirus-related racial discrimination. This study examined the association between pandemic-related stressors, including employment and housing disruptions, coronavirus-related victimization distress, and perceptions of pandemic-associated increase in societal racial biases, and substance use disorder (SUD) risk among Asian, Black, Hispanic/Latino, and non-Hispanic White adults in the U.S. METHODS: Data were collected as part of a larger national survey on substance use during the pandemic. Eligible participants for the current study were 1336 adults self-identified as Asian (8.53%), Black (10.55%), Hispanic/Latino (10.93%), and non-Hispanic White (69.99%). Measures included demographic and COVID-19-related employment, housing, and health items, the coronavirus victimization distress scale (CVD), the coronavirus racial bias scale (CRB), and measures of substance use risk. RESULTS: Across racial/ethnic groups, employment disruption distress and housing disruption due to the pandemic were associated with SUD risk. Binary logistic regression analyses controlling for demographic variables indicated CVD was associated with higher odds of tobacco use risk (AOR = 1.36, 95% CI [1.01, 1.81]) and polysubstance use risk (AOR = 1.87, 95% CI [1.14, 3.06]), yet CRB was unrelated to any SUDs. Logistic regressions for each racial/ethnic group found different patterns of relationships between stressors and risk for SUDs. CONCLUSIONS: Results highlight the significance of examining how the current pandemic has exacerbated racial/ethnic systemic inequalities through COVID-19 related victimization. The data also suggest that across all racial/ethnic groups employment and housing disruptions and perceptions of pandemic instigated increases in societal racial bias are risk factors for SUD. The study calls for further empirical research on substance use prevention and intervention practice sensitive to specific needs of diverse populations during the current and future health crises.

COVID-related social determinants of substance use disorder among diverse U.S. racial ethnic groups

Objective Black, Asian, and Latinx people are disproportionately impacted by the COVID-19 pandemic and were more likely to experience coronavirus-related racial discrimination. This study examined the association between pandemic-related stressors, including employment and housing disruptions, coronavirus-related victimization distress, and perceptions of pandemic-associated increase in societal racial biases, and substance use disorder (SUD) risk among Asian, Black, Latinx, and non-Hispanic White adults in the U.S. Methods Data were collected as part of a larger national survey on substance use during the pandemic. Eligible participants for the current study were 1336 adults self-identified as Asian (8.53%), Black (10.55%), Latinx (10.93%), and non-Hispanic White (69.99%). Measures included demographic and COVID-19-related employment, housing, and health items, the coronavirus victimization distress scale (CVD), the coronavirus racial bias scale (CRB), and measures of substance use risk. Results Across race/ethnicity, employment disruption distress and housing disruption due to the pandemic were associated with SUD risk. Binary logistic regression analyses controlling for demographic variables indicated CVD was associated with higher odds of tobacco use risk (AOR = 1.36, 95% CI [1.01, 1.81]) and polysubstance use risk (AOR = 1.87, 95% CI [1.14, 3.06]), yet CRB was unrelated to any SUDs. Logistic regressions for each racial/ethnic group found different patterns of relationships between stressors and risk for SUDs. Conclusions Results highlight the significance of examining how the current pandemic has exacerbated racial/ethnic systemic inequalities through COVID-19 related victimization. The data also suggest that across all racial/ethnic groups employment and housing disruptions and perceptions of pandemic instigated increases in societal racial bias are risk factors for SUD. The study calls for further empirical research on substance use prevention and intervention practice sensitive to specific needs of diverse populations during the current and future health crises.

D3AI-Spike: A deep learning platform for predicting binding affinity between SARS-CoV-2 spike receptor binding domain with multiple amino acid mutations and human angiotensin-converting enzyme 2.

The number of SARS-CoV-2 spike Receptor Binding Domain (RBD) with multiple amino acid mutations is huge due to random mutations and combinatorial explosions, making it almost impossible to experimentally determine their binding affinities to human angiotensin-converting enzyme 2 (hACE2). Although computational prediction is an alternative way, there is still no online platform to predict the mutation effect of RBD on the hACE2 binding affinity until now. In this study, we developed a free online platform based on deep learning models, namely D3AI-Spike, for quickly predicting binding affinity between spike RBD mutants and hACE2. The models based on CNN and CNN-RNN methods have the concordance index of around 0.8. Overall, the test results of the models are in agreement with the experimental data. To further evaluate the prediction power of D3AI-Spike, we predicted and experimentally determined the binding affinity of a VUM (variants under monitoring) variant IHU (B.1.640.2), which has fourteen amino acid substitutions, including N501Y and E484K, and 9 deletions located in the spike protein. The predicted average affinity score for wild-type RBD and IHU to hACE2 are 0.483 and 0.438, while the determined Kaff values are 5.39 ± 0.38 × 107 L/mol and 1.02 ± 0.47 × 107 L/mol, respectively, demonstrating the strong predictive power of D3AI-Spike. We think D3AI-Spike will be helpful to the viral transmission prediction for the new emerging SARS-CoV-2 variants. D3AI-Spike is now available free of charge at https://www.d3pharma.com/D3Targets-2019-nCoV/D3AI-Spike/index.php.

Asthma mortality attributable to ambient temperatures: A case-crossover study in China.

BACKGROUND: Whether ambient temperature exposure contributes to death from asthma remains unknown to date. We therefore conducted a case-crossover study in China to quantitatively evaluate the association and burden of ambient temperature exposure on asthma mortality. METHODS: Using data from the National Mortality Surveillance System in China, we conducted a time-stratified case-crossover study of 15 888 individuals who lived in Hubei and Jiangsu province, China and died from asthma as the underlying cause in 2015-2019. Individual-level exposures to air temperature and apparent temperature on the date of death and 21 days prior were assessed based on each subject's residential address. Distributed lag nonlinear models based on conditional logistic regression were used to quantify exposure-response associations and calculate fraction and number of deaths attributable to non-optimum ambient temperatures. RESULTS: We observed a reverse J-shaped association between air temperature and risk of asthma mortality, with a minimum mortality temperature of 21.3 °C. Non-optimum ambient temperature is responsible for substantial excess mortality from asthma. In total, 26.3% of asthma mortality were attributable to non-optimum temperatures, with moderate cold, moderate hot, extreme cold and extreme hot responsible for 21.7%, 2.4%, 2.1% and 0.9% of asthma mortality, respectively. The total attributable fraction and number was significantly higher among adults aged less than 80 years in hot temperature. CONCLUSIONS: Exposure to non-optimum ambient temperature, especially moderate cold temperature, was responsible for substantial excess mortality from asthma. These findings have important implications for planning of public-health interventions to minimize the adverse respiratory damage from non-optimum ambient temperature.

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes.

Infection of human peripheral blood cells by SARS-CoV-2 has been debated because immune cells lack mRNA expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease type 2 (TMPRSS2). Herein we demonstrate that resting primary monocytes harbor abundant cytoplasmic ACE2 and TMPRSS2 protein and that circulating exosomes contain significant ACE2 protein. Upon ex vivo TLR4/7/8 stimulation, cytoplasmic ACE2 was quickly translocated to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurred in conjunction with elevated mRNA expression. The rapid translocation of ACE2 to the monocyte cell surface was blocked by the endosomal trafficking inhibitor endosidin 2, suggesting that endosomal ACE2 could be derived from circulating ACE2-containing exosomes. TLR-stimulated monocytes concurrently expressing ACE2 and TMPRSS2 on the cell surface were efficiently infected by SARS-CoV-2, which was significantly mitigated by remdesivir, TMPRSS2 inhibitor camostat, and anti-ACE2 antibody. Mass cytometry showed that ACE2 surface translocation in peripheral myeloid cells from patients with severe COVID-19 correlated with its hyperactivation and PD-L1 expression. Collectively, TLR4/7/8-induced ACE2 translocation with TMPRSS2 expression makes circulating monocytes permissive to SARS-CoV-2 infection.

Exploring the Binding Affinity and Mechanism between ACE2 and the Trimers of Delta and Omicron Spike Proteins by Molecular Dynamics Simulation and Bioassay.

Five major variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged and posed challenges in controlling the pandemic. Among them, the current dominant variant, viz., Omicron, has raised serious concerns about its infectiousness and antibody neutralization. However, few studies pay attention to the effect of the mutations on the dynamic interaction network of Omicron S protein trimers binding to the host angiotensin-converting enzyme 2 (ACE2). In this study, we conducted molecular dynamics (MD) simulations and enzyme linked immunosorbent assay (ELISA) to explore the binding strength and mechanism of wild type (WT), Delta, and Omicron S protein trimers to ACE2. The results showed that the binding capacities of both the two variants' S protein trimers to ACE2 are enhanced in varying degrees, indicating possibly higher cell infectiousness. Energy decomposition and protein-protein interaction network analysis suggested that both the mutational and conserved sites make effects on the increase in the overall affinity through a variety of interactions. The experimentally determined KD values by biolayer interferometry (BLI) and the predicted binding free energies of the RBDs of Delta and Omicron to mAb HLX70 revealed that the two variants may have the high risk of immune evasion from the mAb. These results are not only helpful in understanding the binding strength and mechanism of S protein trimer-ACE2 but also beneficial for drug, especially for antibody development.

Anti-Inflammatory Effects and Molecular Mechanisms of Shenmai Injection in Treating Acute Pancreatitis: Network Pharmacology Analysis and Experimental Verification.

Background: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation. Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266-6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms. Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266-6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice. Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.

Structural Requirements and Plasticity of Receptor-Binding Domain in Human Coronavirus Spike

The most recent human coronaviruses including severe acute respiratory syndrome coronavirus-2 causing severe respiratory tract infection and high pathogenicity bring significant global public health concerns. Infections are initiated by recognizing host cell receptors by coronavirus spike protein S1 subunit, and then S2 mediates membrane fusion. However, human coronavirus spikes undergo frequent mutation, which may result in diverse pathogenesis and infectivity. In this review, we summarize some of these recent structural and mutational characteristics of RBD of human coronavirus spike protein and their interaction with specific human cell receptors and analyze the structural requirements and plasticity of RBD. Stability of spike protein, affinity toward receptor, virus fitness, and infectivity are the factors controlling the viral tropisms. Thus, understanding the molecular details of RBDs and their mutations is critical in deciphering virus evolution. Structural information of spike and receptors of human coronaviruses not only reveals the molecular mechanism of host–microbe interaction and pathogenesis but also helps develop effective drug to control these infectious pathogens and cope with the future emerging coronavirus outbreaks.

Drivers towards Adopting Modular Integrated Construction for Affordable Sustainable Housing: A Total Interpretive Structural Modelling (TISM) Method

This study features the development of a framework to identify drivers towards increasing adoption of modular integrated construction (MiC) methods for affordable sustainable housing (ASH). The rise of offsite construction (OSC) techniques, especially MiC, has been evident in recent years. MiC’s adoption in ASH is still underdeveloped;however, due to various benefits of MiC over conventional construction methods, it is envisioned to be a significant emerging approach for tackling growing housing demand, and ASH in particular. Although a few prior studies identified some factors for utilization of MiC towards ASH, studies to date have not provided a holistic review of drivers or a comprehensive framework of the interrelationships between such drivers. To address this issue, this study utilizes a three-way process including a systematic literature review, semi-structured interviews and the Total Interpretive Structure Modelling (TISM) method to study the drivers for MiC adoption in ASH. Initially, 111 drivers were extracted from a review of 40 studies in the existing literature. Following that, the significant drivers of MiC adoption for ASH were grouped into cost, time, productivity, quality, environmental, social, policy and demand. Drawing on concepts of systems thinking and graph theory, the TISM model for eight drivers was developed from both the literature review and the interview results. Four levels of hierarchy were found among drivers containing linkage, driving, depending and autonomous. Succeeding the steps of TISM and Reachability Matrix (RM) and Matrice d’ Impacts Croises-Multipication Appliqué a Classement (MICMAC) analysis, social drivers were found to have the highest driving and lowest dependency power, followed by productivity and policy drivers. This signifies the importance of social factors for enhancing MiC adoption for ASH. In addition, a strategic framework of boosting MiC adoption in ASH is also presented, highlighting the key stakeholders and strategies for transformation along with conclusions. This study delivers a wider landscape of drivers for MiC-ASH synergy that may assist practitioners, policy makers and relevant stakeholders to better understand the relationships between the drivers.

Rapid and Accurate Detection of SARS Coronavirus 2 by Nanopore Amplicon Sequencing.

Objective: We aimed to evaluate the performance of nanopore amplicon sequencing detection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples. Method: We carried out a single-center, prospective cohort study in a Wuhan hospital and collected a total of 86 clinical samples, including 54 pharyngeal swabs, 31 sputum samples, and 1 fecal sample, from 86 patients with coronavirus disease 2019 (COVID-19) from Feb 20 to May 15, 2020. We performed parallel detection with nanopore-based genome amplification and sequencing (NAS) on the Oxford Nanopore Technologies (ONT) minION platform and routine reverse transcription quantitative polymerase chain reaction (RT-qPCR). In addition, 27 negative control samples were detected using the two methods. The sensitivity and specificity of NAS were evaluated and compared with those of RT-qPCR. Results: The viral read number and reference genome coverage were both significantly different between the two groups of samples, and the latter was a better indicator for SARS-CoV-2 detection. Based on the reference genome coverage, NAS revealed both high sensitivity (96.5%) and specificity (100%) compared with RT-qPCR (80.2 and 96.3%, respectively), although the samples had been stored for half a year before the detection. The total time cost was less than 15 h, which was acceptable compared with that of RT-qPCR (∼2.5 h). In addition, the reference genome coverage of the viral reads was in line with the cycle threshold value of RT-qPCR, indicating that this number could also be used as an indicator of the viral load in a sample. The viral load in sputum might be related to the severity of the infection, particularly in patients within 4 weeks after onset of clinical manifestations, which could be used to evaluate the infection. Conclusion: Our results showed the high sensitivity and specificity of the NAS method for SARS-CoV-2 detection compared with RT-qPCR. The sequencing results were also used as an indicator of the viral load to display the viral dynamics during infection. This study proved the wide application prospect of nanopore sequencing detection for SARS-CoV-2 and may more knowledge about the clinical characteristics of COVID-19.

Twelve-Month Systemic Consequences of Coronavirus Disease 2019 (COVID-19) in Patients Discharged From Hospital: A Prospective Cohort Study in Wuhan, China.

BACKGROUND: Follow-up study of coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. METHODS: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. RESULTS: 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. CONCLUSIONS: Physiological, laboratory, radiological, or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, and liver functions are common in patients who recovered from coronavirus disease 2019 (COVID-19) up to 12 months post-discharge.

The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.

CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity.

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.