Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

Proteomic characterization of acute kidney injury in patients hospitalized with SARS-CoV2 infection.

BACKGROUND: Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. METHODS: Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N = 437), we identified 413 higher plasma abundances of protein targets and 30 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p < 0.05). Of these, 62 proteins were validated in an external cohort (p < 0.05, N = 261). RESULTS: We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p < 0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury. CONCLUSIONS: Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

Acute kidney injury (AKI) is a sudden, sometimes fatal, episode of kidney failure or damage. It is a known complication of COVID-19, albeit through unclear mechanisms. COVID-19 is also associated with kidney dysfunction in the long term, or chronic kidney disease (CKD). There is a need to better understand which patients with COVID-19 are at risk of AKI or CKD. We measure levels of several thousand proteins in the blood of hospitalized COVID-19 patients. We discover and validate sets of proteins associated with severe AKI and CKD in these patients. The markers identified suggest that kidney injury in COVID-19 patients involves damage to kidney cells that reabsorb fluid from urine and reduced blood flow to the heart, causing damage to heart muscles. Our findings might help clinicians to predict kidney injury in patients with COVID-19, and to understand its mechanisms.

Low availability, long wait times, and high geographic disparity of psychiatric outpatient care in the US.

OBJECTIVE: To identify potential barriers to care, this study examined the general psychiatry outpatient new appointment availability in the US, including in-person and telepsychiatry appointments, comparing results between insurance types (Medicaid vs. private insurance), states, and urbanization levels. METHOD: This mystery shopper study investigated 5 US states selected according to Mental Health America Adult Ranking and geography to represent the US mental health care system. Clinics across five selected states were stratified sampled by county urbanization levels. Calls were made during 05/2022-07/2022. Collected data included contact information accuracy, appointment availability, wait time (days), and related information. RESULTS: Altogether, 948 psychiatrists were sampled in New York, California, North Dakota, Virginia, and Wyoming. Overall contact information accuracy averaged 85.3%. Altogether, 18.5% of psychiatrists were available to see new patients with a significantly longer wait time for in-person than telepsychiatry appointments (median = 67.0 days vs median = 43.0 days, p < 0.01). The most frequent reason for unavailability was provider not taking new patients (53.9%). Mental health resources were unevenly distributed, favoring urban areas. CONCLUSION: Psychiatric care has been severely restricted in the US with low accessibility and long wait times. Transitioning to telepsychiatry represents a potential solution for rural disparities in access.

Efficacy and safety of awake prone positioning in the treatment of non-intubated spontaneously breathing patients with COVID-19-related acute respiratory failure: A systematic review and meta-analysis.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, prone positioning has been widely applied for non-intubated, spontaneously breathing patients. However, the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear. We aimed to systematically analyze the outcomes associated with awake prone positioning (APP). Methods: We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science from January 1, 2020, to June 3, 2022. This study included adult patients with acute respiratory failure caused by COVID-19. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was the reported cumulative intubation risk across randomized controlled trials (RCTs), and the effect estimates were calculated as risk ratios (RRs; 95% confidence interval [CI]). Results: A total of 495 studies were identified, of which 10 fulfilled the selection criteria, and 2294 patients were included. In comparison to supine positioning, APP significantly reduced the need for intubation in the overall population (RR=0.84, 95% CI: 0.74-0.95). The two groups showed no significant differences in the incidence of adverse events (RR=1.16, 95% CI: 0.48-2.76). The meta-analysis revealed no difference in mortality between the groups (RR=0.93, 95% CI: 0.77-1.11). Conclusions: APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19. However, it did not significantly reduce mortality in comparison to usual care without prone positioning.

Circulating proteins to predict COVID-19 severity.

Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.

Efficacy and safety of awake prone positioning in the treatment of non-intubated spontaneously breathing patients with COVID-19-related acute respiratory failure: A systematic review and meta-analysis

Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, prone positioning has been widely applied for non-intubated, spontaneously breathing patients. However, the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear. We aimed to systematically analyze the outcomes associated with awake prone positioning (APP). Methods We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science from January 1, 2020, to June 3, 2022. This study included adult patients with acute respiratory failure caused by COVID-19. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was the reported cumulative intubation risk across randomized controlled trials (RCTs), and the effect estimates were calculated as risk ratios (RRs;95% confidence interval [CI]). Results A total of 495 studies were identified, of which 10 fulfilled the selection criteria, and 2294 patients were included. In comparison to supine positioning, APP significantly reduced the need for intubation in the overall population (RR=0.84, 95% CI: 0.74–0.95). The two groups showed no significant differences in the incidence of adverse events (RR=1.16, 95% CI: 0.48–2.76). The meta-analysis revealed no difference in mortality between the groups (RR=0.93, 95% CI: 0.77–1.11). Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19. However, it did not significantly reduce mortality in comparison to usual care without prone positioning.

Impact of Loneliness and Social Isolation on Mental Health Outcomes Among Individuals With Rheumatic Diseases During the COVID-19 Pandemic.

OBJECTIVE: The study objective was to assess mental and social health outcomes for individuals with rheumatic disease during the COVID-19 pandemic and evaluate the relationship of loneliness and social isolation with depression and anxiety. METHODS: We administered an international cross-sectional online survey to individuals with rheumatic disease(s) (≥18 years) between April 2020 and September 2020, with a follow-up survey from December 2020 to February 2021. We used questionnaires to evaluate loneliness (3-item UCLA Loneliness Scale [UCLA-3]), social isolation (Lubben Social Network Scale [LSNS-6]), depression (Patient Health Questionnaire [PHQ-9]), and anxiety (Generalized Anxiety Disorder 7-item [GAD-7] Scale). We used multivariable linear regression models to evaluate the cross-sectional associations of loneliness and social isolation with depression and anxiety at baseline. RESULTS: Seven hundred eighteen individuals (91.4% women, mean age: 45.4 ± 14.2 years) participated in the baseline survey, and 344 completed the follow-up survey. Overall, 51.1% of participants experienced loneliness (UCLA-3 score ≥6) and 30.3% experienced social isolation (LSNS-6 score <12) at baseline. Depression (PHQ-9 score ≥10) and anxiety (GAD-7 score ≥10) were experienced by 42.8% and 34.0% of participants at baseline, respectively. Multivariable models showed that experiencing both loneliness and social isolation, in comparison to experiencing neither, was significantly associated with an average 7.27 higher depression score (ß = 7.27; 95% confidence interval [CI]: 6.08-8.47) and 5.14 higher anxiety score (ß = 5.14; 95% CI: 4.00-6.28). CONCLUSION: Aside from showing substantial experience of loneliness and social isolation during the COVID-19 pandemic, our survey showed significant associations with depression and anxiety. Patient supports to address social health have potential implications for also supporting mental health.

Immunogenicity of COVID-19 vaccines in solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19. OBJECTIVES: This study aimed to evaluate the immunogenicity of COVID-19 vaccines in SOT recipients. DATA SOURCES: Electronic databases were searched for eligible reports published from 1 December 2019 to 31 May 2022. STUDY ELIGIBILITY CRITERIA: We included reports evaluating the humoral immune response (HIR) or cellular immune response rate in SOT recipients after the administration of COVID-19 vaccines. PARTICIPANTS: SOT recipients who received COVID-19 vaccines. ASSESSMENT OF RISK OF BIAS: We used the Newcastle-Ottawa scale to assess bias in case-control and cohort studies. For randomised-controlled trials, the Jadad Scale was used. METHODS: We used a random-effects model to calculate the pooled rates of immune response with 95% CI. We used a risk ratio (RR) with 95% CI for a comparison of immune responses between SOT and healthy controls. RESULTS: A total of 91 reports involving 11 886 transplant recipients (lung: 655; heart: 539; liver: 1946; and kidney: 8746) and 2125 healthy controls revealed pooled HIR rates after the 1st, 2nd, and 3rd COVID-19 vaccine doses in SOT recipients were 9.5% (95% CI, 7-11.9%), 43.6% (95% CI, 39.3-47.8%) and 55.1% (95% CI, 44.7-65.6%), respectively. For specific organs, the HIR rates were still low after 1st vaccine dose (lung: 4.4%; kidney: 9.4%; heart: 13.2%; liver: 29.5%) and 2nd vaccine dose (lung: 28.4%; kidney: 37.6%; heart: 50.3%; liver: 64.5%). CONCLUSIONS: A booster vaccination enhances the immunogenicity of COVID-19 vaccines in SOT; however, a significant share of the recipients still has not built a detectable HIR after receiving the 3rd dose. This finding calls for alternative approaches, including the use of monoclonal antibodies. In addition, lung transplant recipients need urgent booster vaccination to improve the immune response.

Chimeric mRNA-based COVID-19 vaccine induces protective immunity against Omicron and Delta variants.

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the effectiveness of currently approved mRNA vaccines. To achieve wider coverage of VOCs, we first constructed a cohort of mRNAs harboring a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). The mutation abolished the cleavage between the S1 and S2 subunits. Systematic evaluation in vaccinated mice discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. In particular, the neutralizing antibodies (nAb) produced by immunization with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs. However, neither mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original Omicron variant and some sublineages. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we engineered an mRNA-based chimeric immunogen by introducing the receptor-binding domain of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA induced potent and broadly nAbs against Omicron and Delta, which paves the way to developing new vaccine candidates to target emerging variants in the future.

Suicidal Ideation Amongst University Students During the COVID-19 Pandemic: Time Trends and Risk Factors.

OBJECTIVE: Examine time trends in suicidal ideation in post-secondary students over the first three waves of the COVID-19 pandemic in Canada and identify subpopulations of students with increased risk. METHOD: We analysed 14 months of data collected through repeated cross-sectional deployment of the World Health Organization (WHO) World Mental Health-International College Student (WMH-ICS) survey at the University of British Columbia. Estimated log odds weekly trends of 30-day suicidal ideation (yes/no) were plotted against time with adjustments for demographics using binary logistic generalized additive model (GAM). Risk factors for 30-day suicidal ideation frequency (four categories) were examined using the ordered logistic GAM, with a cubic smoothing spline for modelling time trend in obervation weeks and accounting for demographics. RESULTS: Nearly one-fifth (18.9%) of students experienced suicidal ideation in the previous 30 days. While the estimated log odds suggested that binary suicidal ideation was relatively stable across the course of the pandemic, an initial drop followed by an increasing trend was observed. Risk factors for suicidal ideation frequency during the pandemic included identifying as Chinese or as another non-Indigenous ethnic minority; experiencing current symptoms of depression or anxiety; having a history of suicidal planning or attempts; and feeling overwhelmed but unable to get help as a result of COVID-19. Older age was identified as a protective factor. CONCLUSIONS: The general university student population in our study was relatively resilient with respect to suicidal ideation during the first three waves of the pandemic, but trends indicate the possibility of delayed impact. Specific sub-populations were found to be at increased risk and should be considered for targeted support. Further analyses should be undertaken to continue monitoring suicidality trends throughout the remainder of the pandemic and beyond.

Auricular acupressure for adverse events following immunization after COVID-19 vaccine injection: A multicentre, blinded, randomized controlled trial.

BACKGROUND: Some adverse events following immunization (AEFI) were observed in potential corelation with COVID-19 vaccination but without prevention or ongoing trial for it. We aimed to investigate efficacy of auricular acupressure (AuriAc) therapy in preventing AEFI after first dosage of the vaccine. METHODS: We performed a multicentre randomized controlled trial with three arms, including AuriAc, SAuriAc (sham auricular acupressure), and TrAsU (treatment as usual) group, carried out in four medical institutions in Chengdu, China, from March 17th to April 23rd, 2021. We enrolled participants based on eligibility criteria and randomized them into three groups: AuriAc (AEFI-specific auricular points applied, n = 52), SAuriAc (n = 51) or TrAsU (n = 44) group. Primary outcomes were percentages of any AEFI and local pain, and secondary outcomes were percentages who reported other AEFI. They were followed at 1, 3, 5, 7, and 14 days, by phone or online, with severity evaluated. RESULTS: 147 participants (73.47% females) were included with median age as 31 years (25-45, IQR). One day after the injection, participants in AuriAc group reported significant reduction on percentages of any AEFI [intention-to-treat, difference of percentage (DP) = -20.13, 95%CI: - 0.39, - 0.02, p = 0.01; per-protocol, DP = -22.21, 95%CI: - 0.40, - 0.03, P = 0.02] and local pain (per-protocol, DP = -18.40, 95%CI: -0.36, -0.01, P = 0.04), compared with TrAsU group. The effects were slight at other follow-up days and for other outcomes, and with a low percentage of mild local allergic reactions. CONCLUSIONS: We firstly explored potential of AuriAc for preventing AEFI related to COVID-19 vaccine injection, which is beneficial for the vaccine recipients, but evidence is limited. TRIAL REGISTRATION: chictr.org.cn no. ChiCTR2100043210 (http://www.chictr.org.cn/showproj.aspx?proj=121519).

Detection of SARS-CoV-2 Antibodies in Oral Fluid Using a Magnetic Particle-Based Chemiluminescence Immunoassay - Beijing Municipality, China, 2021.

Introduction: Oral fluids (OFs) have been broadly used as non-invasive samples for evaluating protective IgG antibodies from natural infection or vaccination, especially in pediatric populations. Methods: Paired OF and serum were collected from both individuals who received a booster dose of the inactive coronavirus disease 2019 (COVID-19) vaccine as well as those who did not have a history of COVID-19 vaccination and infection (as the control group). The total human IgG antibody (HIgG) content was evaluated as a marker of OF sampling quality. An in-house adapted magnetic particle-based chemiluminescence immunoassay was used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody detection in the OF. The SARS-CoV-2 IgG antibody in the serum samples was detected using a commercial immunoassay. Results: In total, 579 paired OF and serum samples were collected. An additional 172 OF samples were collected from preschool children. The results indicated that the HIgG concentration in qualified OF samples should be higher than 0.3 µg/mL. Compared to the serum assay, the in-house OF immunoassay for detecting IgG antibodies against SARS-CoV-2 had 95.06% accuracy, 95.03% sensitivity, and 100% specificity. Conclusions: Overall, the in-house immunoassay for detecting SARS-CoV-2 IgG antibodies in OF showed high potential for application towards serological surveillance and immunization effect assessment after large-scale, inactive COVID-19 vaccination in China.

Immune Persistence against SARS-CoV-2 after Primary and Booster Immunization in Humans: A Large-Scale Prospective Cohort Study.

Amid the ongoing global COVID-19 pandemic, limited literature exists on immune persistence after primary immunization and the immunogenic features of booster vaccines administered at different time intervals. Therefore, this study aimed to determine the immune attenuation of neutralizing antibodies against the SARS-CoV-2 wild-type strain, and Delta and Omicron variants 12 months after the primary administration of the COVID-19 inactivated vaccine and evaluate the immune response after a booster administration at different time intervals. A total of 514 individuals were followed up after primary immunization and were vaccinated with a booster. Neutralizing antibodies against the wild-type strain and Delta and Omicron variant spike proteins were measured using pseudovirus neutralization assays. The geometric mean titers (GMTs) after the primary and booster immunizations were 12.09 and 61.48 for the wild-type strain, 11.67 and 40.33 for the Delta variant, and 8.51 and 29.31 for the Omicron variant, respectively. The GMTs against the wild-type strain declined gradually during the 12 months after the primary immunization, and were lower against the two variants. After implementing a booster immunization with a 6 month interval, the GMTs against the wild-type strain were higher than those obtained beyond the 7 month interval; however, the GMTs against the two variants were not statistically different across 3-12 month intervals. Overall, SARS-CoV-2 variants showed remarkable declines in immune persistence, especially against the Omicron variant. The booster administration interval could be shortened to 3 months in endemic areas of the Omicron variant, whereas an appropriate prolonging of the booster administration interval did not affect the booster immunization effect.

The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.

INTRODUCTION: Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. METHODS: We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support. RESULTS: 580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p < 3.4 × 10-4). Three clusters were formed by 108 highly correlated proteins that replicated in both cohorts, making it difficult to determine which proteins have a true causal effect on severe COVID-19. Six proteins showed sex differences in levels over time, of which 3 were also associated with severe COVID-19: CCL26, IL1RL2, and IL3RA, providing insights to better understand the marked differences in outcomes by sex. CONCLUSIONS: Severe COVID-19 is associated with large changes in 69 immune-related proteins. Further, five proteins were associated with sex differences in outcomes. These results provide direct insights into immune-related proteins that are strongly influenced by severe COVID-19 infection.

Exploration of the Potential Link, Hub Genes, and Potential Drugs for Coronavirus Disease 2019 and Lung Cancer Based on Bioinformatics Analysis.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) has a huge influence on global public health and the economy. Lung cancer is one of the high-risk factors of COVID-19, but the molecular mechanism of lung cancer and COVID-19 is still unclear, and further research is needed. Therefore, we used the transcriptome information of the public database and adopted bioinformatics methods to identify the common pathways and molecular biomarkers of lung cancer and COVID-19 to further understand the connection between them. The two RNA-seq data sets in this study-GSE147507 (COVID-19) and GSE33532 (lung cancer)-were both derived from the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs) for lung cancer and COVID-19 patients. We conducted Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis and found some common features between lung cancer and COVID-19. We also performed TFs-gene, miRNAs-gene, and gene-drug analyses. In total, 32 DEGs were found. A protein-protein interaction (PPI) network was constructed by DEGs, and 10 hub genes were screened. Finally, the identified drugs may be helpful for COVID-19 treatment.

Ångstrom-scale silver particles potently combat SARS-CoV-2 infection by suppressing the ACE2 expression and inflammatory responses.

The SARS-CoV-2 pandemic has become a severe global public health event, and the development of protective and therapeutic strategies is urgently needed. Downregulation of angiotensin converting enzyme 2 (ACE2; one of the important SARS-CoV-2 entry receptors) and aberrant inflammatory responses (cytokine storm) are the main targets to inhibit and control COVID-19 invasion. Silver nanomaterials have well-known pharmaceutical properties, including antiviral, antibacterial, and anticancer properties. Here, based on a self-established metal evaporation-condensation-size graded collection system, smaller silver particles reaching the Ångstrom scale (AgÅPs) were fabricated and coated with fructose to obtain a stabilized AgÅP solution (F-AgÅPs). F-AgÅPs potently inactivated SARS-CoV-2 and prevented viral infection. Considering the application of anti-SARS-CoV-2, a sterilized F-AgÅP solution was produced via spray formulation. In our model, the F-AgÅP spray downregulated ACE2 expression and attenuated proinflammatory factors. Moreover, F-AgÅPs were found to be rapidly eliminated to avoid respiratory and systemic toxicity in this study as well as our previous studies. This work presents a safe and potent anti-SARS-CoV-2 agent using an F-AgÅP spray.

Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice.

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) was increasingly recognized as one of the most severe acute hyperimmune response of coronavirus disease 2019 (COVID-19). Clofazimine (CFZ) has attracted attention due to its anti-inflammatory property in immune diseases as well as infectious diseases. However, the role and potential molecular mechanism of CFZ in anti-inflammatory responses remain unclear. METHODS: We analyze the protein expression profiles of CFZ and LPS from Raw264.7 macrophages using quantitative proteomics. Next, the protective effect of CFZ on LPS-induced inflammatory model is assessed, and its underlying mechanism is validated by molecular biology analysis. RESULTS: LC-MS/MS-based shotgun proteomics analysis identified 4746 (LPS) and 4766 (CFZ) proteins with quantitative information. The key proteins and their critical signal transduction pathways including TLR4/NF-κB/HIF-1α signaling was highlighted, which was involved in multiple inflammatory processes. A further analysis of molecular biology revealed that CFZ could significantly inhibit the proliferation of Raw264.7 macrophages, decrease the levels of TNF-α and IL-1ß, alleviate lung histological changes and pulmonary edema, improve the survival rate, and down-regulate TLR4/NF-κB/HIF-1α signaling in LPS model. CONCLUSION: This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease.

Severe COVID-19 outcomes among patients with autoimmune rheumatic diseases or transplantation: a population-based matched cohort study

Objectives To assess the risk of severe COVID-19 outcomes in patients with autoimmune rheumatic diseases (ARDs) and transplant recipients compared with matched general population comparators. Design Population-based matched cohort study using administrative health data sets. Setting British Columbia, Canada. Participants All adults with test-positive SARS-CoV-2 infections. SARS-CoV-2-positive patients with ARDs and those with transplantation were matched to SARS-CoV-2-positive general population comparators on age (±5 years), sex, month/year of initial positive SARS-CoV-2 test and health authority. Outcome measures COVID-19-related hospitalisations, intensive care unit (ICU) admissions, invasive ventilation and COVID-19-specific mortality. We performed multivariable conditional logistic regression models adjusting for socioeconomic status, Charlson Comorbidity Index, hypertension, rural address and number of previous COVID-19 PCR tests. Results Among 6279 patients with ARDs and 222 transplant recipients, all SARS-CoV-2 test positive, risk of hospitalisation was significantly increased among patients with ARDs (overall ARDs (adjusted OR (aOR) 1.30;95% CI 1.19 to 1.43));highest within ARDs: adult systemic vasculitides (aOR 2.18;95% CI 1.17 to 4.05) and transplantation (aOR 10.56;95% CI 6.88 to 16.22). Odds of ICU admission were significantly increased among patients with ARDs (overall ARDs (aOR 1.30;95% CI 1.11 to 1.51));highest within ARDs: ankylosing spondylitis (aOR 2.03;95% CI 1.18 to 3.50) and transplantation (aOR 8.13;95% CI 4.76 to 13.91). Odds of invasive ventilation were significantly increased among patients with ARDs (overall ARDs (aOR 1.60;95% CI 1.27 to 2.01));highest within ARDs: ankylosing spondylitis (aOR 2.63;95% CI 1.14 to 6.06) and transplantation (aOR 8.64;95% CI 3.81 to 19.61). Risk of COVID-19-specific mortality was increased among patients with ARDs (overall ARDs (aOR 1.24;95% CI 1.05 to 1.47));highest within ARDs: ankylosing spondylitis (aOR 2.15;95% CI 1.02 to 4.55) and transplantation (aOR 5.48;95% CI 2.82 to 10.63). Conclusions The risk of severe COVID-19 outcomes is increased in certain patient groups with ARDs or transplantation, although the magnitude differs across individual diseases. Strategies to mitigate risk, such as booster vaccination, prompt diagnosis and early intervention with available therapies, should be prioritised in these groups according to risk.