Efficacy of mRNA-1273 and Novavax ancestral or BA.1 spike booster vaccines against SARS-CoV-2 BA.5 infection in non-human primates.

Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.1 spike protein version (NVX-CoV2515). All three booster vaccines induced a strong BA.1 cross-reactive binding antibody and changed immunoglobulin G dominance from IgG1 to IgG4 in the serum. All three booster vaccines also induced strong and comparable neutralizing antibody responses against multiple variants of concern, including BA.5 and BQ.1.1, along with long-lived plasma cells in the bone marrow. The ratio of BA.1 to WA-1 spike-specific antibody-secreting cells in the blood was higher in NVX-CoV2515 animals compared to NVX-CoV2373 animals, suggesting a better recall of BA.1 specific memory B cells by the BA.1 spike-specific vaccine compared to the ancestral spike-specific vaccine. Further, all three booster vaccines induced low levels of spike-specific CD4 but not CD8 T cell responses in the blood. Following challenge with SARS-CoV-2 BA.5 variant, all three vaccines showed strong protection in the lungs and controlled virus replication in the nasopharynx. In addition, both Novavax vaccines blunted viral replication in nasopharynx at day 2. The protection against SARS-CoV-2 BA.5 infection in the upper respiratory airways correlated with binding, neutralizing, and ADNP activities of the serum antibody. These data have important implications for COVID-19 vaccine development, as vaccines that lower nasopharyngeal virus may help to reduce transmission.

Stroke Mortality Among Black and White Adults Aged ≥35 Years Before and During the COVID-19 Pandemic - United States, 2015-2021.

Stroke is the fifth leading cause of death and a leading cause of long-term disability in the United States (1). Although stroke death rates have declined since the 1950s, age-adjusted rates remained higher among non-Hispanic Black or African American (Black) adults than among non-Hispanic White (White) adults (1,2). Despite intervention efforts to reduce racial disparities in stroke prevention and treatment through reducing stroke risk factors, increasing awareness of stroke symptoms, and improving access to treatment and care for stroke (1,3), Black adults were 45% more likely than were White adults to die from stroke in 2018.* In 2019, age-adjusted stroke death rates (AASDRs) (stroke deaths per 100,000 population) were 101.6 among Black adults and 69.1 among White adults aged ≥35 years. Stroke deaths increased during the early phase of the COVID-19 pandemic (March-August 2020), and minority populations experienced a disproportionate increase (4). The current study examined disparities in stroke mortality between Black and White adults before and during the COVID-19 pandemic. Analysts used National Vital Statistics System (NVSS) mortality data accessed via CDC WONDER† to calculate AASDRs among Black and White adults aged ≥35 years prepandemic (2015-2019) and during the pandemic (2020-2021). Compared with that during the prepandemic period, the absolute difference in AASDR between Black and White adults during the pandemic was 21.7% higher (31.3 per 100,000 versus 38.0). During the pandemic period, an estimated 3,835 excess stroke deaths occurred among Black adults (9.4% more than expected) and 15,125 among White adults (6.9% more than expected). These findings underscore the importance of identifying the major factors contributing to the widened disparities; implementing prevention efforts, including the management and control of hypertension, high blood cholesterol, and diabetes; and developing tailored interventions to reduce disparities and advance health equity in stroke mortality between Black and White adults. Stroke is a serious medical condition that requires emergency care. Warning signs of a stroke include sudden face drooping, arm weakness, and speech difficulty. Immediate notification of Emergency Medical Services by calling 9-1-1 is critical upon recognition of stroke signs and symptoms.

In Silico Identification of Anti-SARS-CoV-2 Medicinal Plants Using Cheminformatics and Machine Learning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, is spreading rapidly and has caused hundreds of millions of infections and millions of deaths worldwide. Due to the lack of specific vaccines and effective treatments for COVID-19, there is an urgent need to identify effective drugs. Traditional Chinese medicine (TCM) is a valuable resource for identifying novel anti-SARS-CoV-2 drugs based on the important contribution of TCM and its potential benefits in COVID-19 treatment. Herein, we aimed to discover novel anti-SARS-CoV-2 compounds and medicinal plants from TCM by establishing a prediction method of anti-SARS-CoV-2 activity using machine learning methods. We first constructed a benchmark dataset from anti-SARS-CoV-2 bioactivity data collected from the ChEMBL database. Then, we established random forest (RF) and support vector machine (SVM) models that both achieved satisfactory predictive performance with AUC values of 0.90. By using this method, a total of 1011 active anti-SARS-CoV-2 compounds were predicted from the TCMSP database. Among these compounds, six compounds with highly potent activity were confirmed in the anti-SARS-CoV-2 experiments. The molecular fingerprint similarity analysis revealed that only 24 of the 1011 compounds have high similarity to the FDA-approved antiviral drugs, indicating that most of the compounds were structurally novel. Based on the predicted anti-SARS-CoV-2 compounds, we identified 74 anti-SARS-CoV-2 medicinal plants through enrichment analysis. The 74 plants are widely distributed in 68 genera and 43 families, 14 of which belong to antipyretic detoxicate plants. In summary, this study provided several medicinal plants with potential anti-SARS-CoV-2 activity, which offer an attractive starting point and a broader scope to mine for potentially novel anti-SARS-CoV-2 drugs.

Predicting flow diverter sizing using the AneuGuideTM software: a validation study.

BACKGROUND: Stent sizing remains a challenging task for flow diverter implantation because of stent foreshortening. In this study, we aimed to quantify the change in length after implantation and assess the error in length prediction using AneuGuideTM software. METHODS: In a retrospective cohort of 101 patients with 102 aneurysms undergoing treatment with a pipeline embolization device (PED; Covidien, Irvine, California, USA), we used AneuGuideTM software to obtain measured lengths (ML) and calculated lengths (CL) after stent implantation. Stent elongation was defined as the ratio of ML-LL to the labeled length (LL). Simulation error was defined as the ratio of the absolute value of CL-ML to ML. The correlation and consistency between ML and LL and between ML and CL were analyzed using Pearson's correlation test and the Bland-Altman plot. Statistical significance was set at p<0.05. RESULTS: The mean elongation of ML was 32.6% (range 26.3-109.2%). Moderate consistency was observed between LL and ML (ρ=0.74, p<0.001). With the AneuGuideTM software, the mean simulation error was 6.6% (range 0.32-21.2%). Pearson's correlation test and the Bland-Altman plot showed a high correlation and consistency between ML and CL (ρ=0.96, p<0.001). CONCLUSION: Labeled length provides only a low reference value for predicting the actual length of the flow diverter after implantation. The high consistency between ML and CL obtained from AneuGuideTM software shows its great potential for the optimization of the flow diverter sizing process.

Analysis of melanoma tumor antigens and immune subtypes for the development of mRNA vaccine.

Melanoma has a high degree of malignancy and mortality. While there are some hopeful clinical trials for melanoma treatment in progress, they have not yet to yield significant long-term cure rates. Cancer vaccines including mRNA are currently one of the most promising strategy for tumor immunotherapy. The aim of this study was to analyze the potential tumor antigens in melanoma that could be used to develop mRNA vaccines and identify suitable vaccine populations. The gene expression data and complete clinical information of 471 melanoma samples and 1 normal tissue were retrieved from TCGA. Then, 812 samples of normal skin and their corresponding gene expression data were obtained from GTEx. Overexpressed genes, mutated genes and IRDEGs are used to identify potential tumor antigens. The relationship between the expression level of potential antigen and prognosis was analyzed in GEPIA, and then the immune cell infiltration was estimated based on TIMER algorithm. The expression profiles of IRDEGs were used to identify consensus clusters and immune subtypes of melanoma. Finally, mutational status and immune microenvironment characterization in immune subtypes were analyzed. Five tumor antigens (PTPRC, SIGLEC10, CARD11, LILRB1, ADAMDEC1) were identified as potential tumor antigens according to overexpressed genes, mutated genes and immune-related genes. They were all associated with OS, DFS and APCs. We identified two immune subtypes of melanoma, named IS1 and IS2, which exhibit different clinical features and immune landscapes. Based on the different immune landscape, we may conclude that IS1 is immunophenotypically "cold", while IS2 is "hot". The present research implicates that PTPRC, SIGLEC10, CARD11, LILRB1 and ADAMDEC1 may be the antigenic targets for melanoma mRNA vaccines and IS2 patients may be more effective to these vaccines.

Pyroptosis in the lung and spleen of patients died from COVID-19

The purpose of this study was to investigate the expression of pyroptosis-related factors (NLRP3, IL-18, NF-κB, HMGB-1, and GSDMD) in patients who died of COVID-19. The expression levels of NLRP3, IL-18, NF-κB, HMGB-1, and GSDMD in lung and spleen tissues of the COVID-19 group and the control group were detected by tissue immunofluorescence. The control group includes lung tissues and spleen tissues of two patients who died unexpectedly without SARS-CoV-2 infection, and the COVID-19 group includes the lung and spleen tissues of three patients who died of SARS-CoV-2 virus infection. The positive rates of NF-κB, NLRP3, IL-18, and GSDMD in the lung tissues from the control group and COVID-19 group were 9.8% vs 73.4% (p = 0.000), 5.5% vs 63.6% (p = 0.000), 24.4% vs 76.2% (p = 0.000), and 17.5% and 46.8% (p = 0.000) respectively. The positive rates of NF-κB, NLRP3, IL-18, HMGB-1, and GSDMD in the spleen tissues from the control group and COVID-19 group were 20.6% vs 71.2% (p = 0.000), 18.9% vs 72.0% (p = 0.000), 15.2% vs 64.8% (p = 0.000), 27.6% vs 69.2% (p = 0.000), and 23% and 48.8% (p = 0.000), respectively. The positive rates of SARS-CoV-2 spike protein in the CD68 positive cells of the lung and spleen in the control group and COVID-19 group were 2.5% vs 56.8% (p = 0.000);3.0% vs 64.9% (p = 0.000) respectively. The rates of NF-κB positive nuclei in the control group and COVID-19 group were 13.4% vs 51.4% (p = 0.000) in the lung and 38.2% vs 59.3% (p = 0.000) in the spleen. The rates of HMGB-1 positive cytoplasm in the control and the COVID-19 group were 19.7% vs 50.3% (p = 0.000) in the lung and 12.3% vs 45.2% (p = 0.000) in the spleen. The targets of SARS-CoV-2 are the lung and spleen, where increased macrophages could be involved in the up-regulation of pyroptosis-related inflammatory factors such as NF-κB, HMGB-1, NLRP3, IL-18, and GSDMD.

Venous thromboembolism among Medicare acute ischaemic stroke patients with and without COVID-19.

BACKGROUND: COVID-19 is associated with an increased risk of venous thromboembolism (VTE). This study examined the prevalence of VTE among acute ischaemic stroke (AIS) patients with and without a history of COVID-19. METHODS: We identified AIS hospitalisations of Medicare fee-for-service (FFS) beneficiaries aged ≥65 years from 1 April 2020 to 31 March 2022. We compared the prevalence and adjusted prevalence ratio of VTE among AIS patients with and without a history of COVID-19. RESULTS: Among 283 034 Medicare FFS beneficiaries with AIS hospitalisations, the prevalence of VTE was 4.51%, 2.96% and 2.61% among those with a history of hospitalised COVID-19, non-hospitalised COVID-19 and without COVID-19, respectively. As compared with patients without a history of COVID-19, the prevalence of VTE among patients with a history of hospitalised or non-hospitalised COVID-19 were 1.62 (95% CI 1.54 to 1.70) and 1.13 (95% CI 1.03 to 1.23) times greater, respectively. CONCLUSIONS: There appeared to be a notably higher prevalence of VTE among Medicare beneficiaries with AIS accompanied by a current or prior COVID-19. Early recognition of coagulation abnormalities and appropriate interventions may help improve patients' clinical outcomes.

A High-Sensitivity Gravimetric Biosensor Based on S1 Mode Lamb Wave Resonator.

The development of MEMS acoustic resonators meets the increasing demand for in situ detection with a higher performance and smaller size. In this paper, a lithium niobate film-based S1 mode Lamb wave resonator (HF-LWR) for high-sensitivity gravimetric biosensing is proposed. The fabricated resonators, based on a 400-nm X-cut lithium niobate film, showed a resonance frequency over 8 GHz. Moreover, a PMMA layer was used as the mass-sensing layer, to study the performance of the biosensors based on HF-LWRs. Through optimizing the thickness of the lithium niobate film and the electrode configuration, the mass sensitivity of the biosensor could reach up to 74,000 Hz/(ng/cm2), and the maximum value of figure of merit (FOM) was 5.52 × 107, which shows great potential for pushing the performance boundaries of gravimetric-sensitive acoustic biosensors.

The Third dose of CoronVac vaccination induces broad and potent adaptive immune responses that recognize SARS-CoV-2 Delta and Omicron variants.

The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of the booster vaccination of coronavirus disease 2019 (COVID-19). The inactivated vaccine, CoronaVac, is the most widely supplied COVID-19 vaccine globally. Whether the CoronaVac booster elicited adaptive responses that cross-recognize SARS-CoV-2 variants of concern (VoCs) among 77 healthy subjects receiving the third dose of CoronaVac were explored. After the boost, remarkable elevated spike-specific IgG and IgA responses, as well as boosted neutralization activities, were observed, despite 3.0-fold and 5.9-fold reduced neutralization activities against Delta and Omicron strains compared to that of the ancestral strain. Furthermore, the booster dose induced potent B cells and memory B cells that cross-bound receptor-binding domain (RBD) proteins derived from VoCs, while Delta and Omicron RBD-specific memory B cell recognitions were reduced by 2.7-fold and 4.2-fold compared to that of ancestral strain, respectively. Consistently, spike-specific circulating follicular helper T cells (cTfh) significantly increased and remained stable after the boost, with a predominant expansion towards cTfh17 subpopulations. Moreover, SARS-CoV-2-specific CD4+ and CD8+ T cells peaked and sustained after the booster. Notably, CD4+ and CD8+ T cell recognition of VoC spike was largely preserved compared to the ancestral strain. Individuals without generating Delta or Omicron neutralization activities had comparable levels of CD4+ and CD8+ T cells responses as those with detectable neutralizing activities. Our study demonstrated that the CoronaVac booster induced broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.

Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines.

The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.

Non-clinical immunogenicity, biodistribution and toxicology evaluation of a chimpanzee adenovirus-based COVID-19 vaccine in rat and rhesus macaque.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 has rapidly expanded into a serious global pandemic. Due to the high morbidity and mortality of COVID-19, there is an urgent need to develop safe and effective vaccines. AdC68-19S is an investigational chimpanzee adenovirus serotype 68 (AdC68) vector-based vaccine which encodes the full-length spike protein of SARS-CoV-2. Here, we evaluated the immunogenicity, biodistribution and safety profiles of the candidate vaccine AdC68-19S in Sprague Dawley (SD) rat and rhesus macaque under GLP conditions. To characterize the biodistribution profile of AdC68-19S, SD rats were given a single intramuscular injection of AdC68-19S 2 × 1011 VP/dose. Designated organs were collected on day 1, day 2, day 4, day 8 and day 15. Genomic DNA was extracted from all samples and was further quantified by real-time quantitative polymerase chain reaction (qPCR). To characterize the toxicology and immunogenicity profiles of AdC68-19S, the rats and rhesus macaques were injected intramuscularly with AdC68-19S up to 2 × 1011vp/dose or 4 × 1011vp/dose (2 and fourfold the proposed clinical dose of 1 × 1011vp/dose) on two or three occasions with a 14-day interval period, respectively. In addition to the conventional toxicological evaluation indexes, the antigen-specific cellular and humoral responses were evaluated. We proved that multiple intramuscular injections could elicit effective and long-lasting neutralizing antibody responses and Th1 T cell responses. AdC68-19S was mainly distributed in injection sites and no AdC68-19S related toxicological reaction was observed. In conclusion, these results have shown that AdC68-19S could induce an effective immune response with a good safety profile, and is a promising candidate vaccine against COVID-19.

COVID-19 and Risk of Acute Ischemic Stroke Among Medicare Beneficiaries Aged 65 Years or Older: Self-Controlled Case Series Study.

BACKGROUND AND OBJECTIVES: Findings of association between coronavirus disease 2019 (COVID-19) and stroke remain inconsistent, ranging from significant association to absence of association to less than expected ischemic stroke among hospitalized patients with COVID-19. The current study examined the association between COVID-19 and risk of acute ischemic stroke (AIS). METHODS: We included 37,379 Medicare fee-for-service (FFS) beneficiaries aged ≥65 years diagnosed with COVID-19 from April 1, 2020, through February 28, 2021, and AIS hospitalization from January 1, 2019, through February 28, 2021. We used a self-controlled case series design to examine the association between COVID-19 and AIS and estimated the incidence rate ratios (IRRs) by comparing incidence of AIS in risk periods (0-3, 4-7, 8-14, 15-28 days after diagnosis of COVID-19) vs control periods. RESULTS: Among 37,379 Medicare FFS beneficiaries with COVID-19 and AIS, the median age at diagnosis of COVID-19 was 80.4 (interquartile range 73.5-87.1) years and 56.7% were women. When AIS at day of exposure (day = 0) was included in the risk periods, IRRs at 0-3, 4-7, 8-14, and 15-28 days following COVID-19 diagnosis were 10.3 (95% confidence interval 9.86-10.8), 1.61 (1.44-1.80), 1.44 (1.32-1.57), and 1.09 (1.02-1.18); when AIS at day 0 was excluded in the risk periods, the corresponding IRRs were 1.77 (1.57-2.01) (day 1-3), 1.60 (1.43-1.79), 1.43 (1.31-1.56), and 1.09 (1.01-1.17), respectively. The association appeared to be stronger among younger beneficiaries and among beneficiaries without prior history of stroke but largely consistent across sex and race/ethnicities. DISCUSSION: Risk of AIS among Medicare FFS beneficiaries was 10 times (day 0 cases in the risk period) as high during the first 3 days after diagnosis of COVID-19 as during the control period and the risk associated with COVID-19 appeared to be stronger among those aged 65-74 years and those without prior history of stroke. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased risk of AIS in the first 3 days after diagnosis in Medicare FFS beneficiaries ≥65 years of age.

Dynamic SARS-CoV-2-specific B-cell and T-cell responses following immunization with an inactivated COVID-19 vaccine.

OBJECTIVE: The dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive. METHODS: In a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4+ and CD8+ T cells and their memory subsets were simultaneously measured in this cohort. RESULTS: SARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969-97065) after two doses and rapidly declined (GMT 502, 212-1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2-9). Spike-specific circulating B cells (0.60%, 0.46-0.73% of total B cells) and memory B cells (1.18%, 0.92-1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23-0.43%; 0.87%, 0.05-1.67%, respectively). SARS-CoV-2-specific circulating CD4+ T cells (0.57%, 0.47-0.66%) and CD8+ T cells (1.29%, 1.04-1.54%) were detected at T3. At T4, 0.78% (0.43-1.20%) of memory CD4+ T cells and 0.68% (0.29-1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51-0.75%) of CD4+ T cells and 0.47% (0.38-0.58%) of CD8+ T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4+ T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8+ T cells (r 0.48, p <0.0001). CONCLUSIONS: CoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.

Cell death and pathological findings of the spleen in COVID-19 patients.

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.

Risks, characteristics, and control strategies of disinfection-residual-bacteria (DRB) from the perspective of microbial community structure.

The epidemic of COVID-19 has aroused people's particular attention to biosafety. A growing number of disinfection products have been consumed during this period. However, the flaw of disinfection has not received enough attention, especially in water treatment processes. While cutting down the quantity of microorganisms, disinfection processes exert a considerable selection effect on bacteria and thus reshape the microbial community structure to a great extent, causing the problem of disinfection-residual-bacteria (DRB). These systematic and profound changes could lead to the shift in regrowth potential, bio fouling potential, as well as antibiotic resistance level and might cause a series of potential risks. In this review, we collected and summarized the data from the literature in recent 10 years about the microbial community structure shifting of natural water or wastewater in full-scale treatment plants caused by disinfection. Based on these data, typical DRB with the most reporting frequency after disinfection by chlorine-containing disinfectants, ozone disinfection, and ultraviolet disinfection were identified and summarized, which were the bacteria with a relative abundance of over 5% in the residual bacteria community and the bacteria with an increasing rate of relative abundance over 100% after disinfection. Furthermore, the phylogenic relationship and potential risks of these typical DRB were also analyzed. Twelve out of fifteen typical DRB genera contain pathogenic strains, and many were reported of great secretion ability. Pseudomonas and Acinetobacter possess multiple disinfection resistance and could be considered as model bacteria in future studies of disinfection. We also discussed the growth, secretion, and antibiotic resistance characteristics of DRB, as well as possible control strategies. The DRB phenomenon is not limited to water treatment but also exists in the air and solid disinfection processes, which need more attention and more profound research, especially in the period of COVID-19.

COVID-19 Pandemic and Quality of Care and Outcomes of Acute Stroke Hospitalizations: the Paul Coverdell National Acute Stroke Program.

INTRODUCTION: Studies documented significant reductions in emergency department visits and hospitalizations for acute stroke during the COVID-19 pandemic. A limited number of studies assessed the adherence to stroke performance measures during the pandemic. We examined rates of stroke hospitalization and adherence to stroke quality-of-care measures before and during the early phase of pandemic. METHODS: We identified hospitalizations with a clinical diagnosis of acute stroke or transient ischemic attack among 406 hospitals who contributed data to the Paul Coverdell National Acute Stroke Program. We used 10 performance measures to examine the effect of the pandemic on stroke quality of care. We compared data from 2 periods: pre-COVID-19 (week 11-24 in 2019) and COVID-19 (week 11-24 in 2020). We used χ2 tests for differences in categorical variables and the Wilcoxon-Mann-Whitney rank test or Kruskal-Wallis test for continuous variables. RESULTS: We identified 64,461 hospitalizations. We observed a 20.2% reduction in stroke hospitalizations (from 35,851 to 28,610) from the pre-COVID-19 period to the COVID-19 period. Hospitalizations among patients aged 85 or older, women, and non-Hispanic White patients declined the most. A greater percentage of patients aged 18 to 64 were hospitalized with ischemic stroke during COVID-19 than during pre-COVID-19 (34.4% vs 32.5%, P < .001). Stroke severity was higher during COVID-19 than during pre-COVID-19 for both hemorrhagic stroke and ischemic stroke, and in-hospital death among patients with ischemic stroke increased from 4.3% to 5.0% (P = .003) during the study period. We found no differences in rates of receiving care across stroke type during the study period. CONCLUSION: Despite a significant reduction in stroke hospitalizations, more severe stroke among hospitalized patients, and an increase in in-hospital death during the pandemic period, we found no differences in adherence to quality of stroke care measures.

Stroke Hospitalizations Before and During COVID-19 Pandemic Among Medicare Beneficiaries in the United States.

[Figure: see text].

Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection.

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

Potent RBD-specific neutralizing rabbit monoclonal antibodies recognize emerging SARS-CoV-2 variants elicited by DNA prime-protein boost vaccination.

Global concerns arose as the emerged and rapidly spreading SARS-CoV-2 variants might escape host immunity induced by vaccination. In this study, a heterologous prime-boost immunization strategy for COVID-19 was designed to prime with a DNA vaccine encoding wild type (WT) spike protein receptor-binding domain (RBD) followed by S1 protein-based vaccine in rabbits. Four vaccine-elicited rabbit monoclonal antibodies (RmAbs), including 1H1, 9H1, 7G5, and 5E1, were isolated for biophysical property, neutralization potency and sequence analysis. All RmAbs recognized RBD or S1 protein with KD in the low nM or sub nM range. 1H1 and 9H1, but neither 7G5 nor 5E1, can bind to all RBD protein variants derived from B.1.351. All four RmAbs were able to neutralize wild type (WT) SARS-CoV-2 strain in pseudovirus assay, and 1H1 and 9H1 could neutralize the SARS-CoV-2 WT authentic virus with IC50 values of 0.136 and 0.026 µg/mL, respectively. Notably, 1H1 was able to neutralize all 6 emerging SARS-CoV-2 variants tested including D614G, B.1.1.7, B.1.429, P.1, B.1.526, and B.1.351 variants, and 5E1 could neutralize against the above 5 variants except P.1. Epitope binning analysis revealed that 9H1, 5E1 and 1H1 recognized distinct epitopes, while 9H1 and 7G5 may have overlapping but not identical epitope. In conclusion, DNA priming protein boost vaccination was an effective strategy to induce RmAbs with potent neutralization capability against not only SARS-CoV-2 WT strain but also emergent variants, which may provide a new avenue for effective therapeutics and point-of-care diagnostic measures.