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1.
    
《Cell host & microbe》2022,30(9):1255-1268.e5
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  总被引:1,自引:0,他引:1  
《Cell》2021,184(19):4848-4856
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The confirmed case fatality rate for the coronavirus disease 2019 (COVID-19) in Ghana has dropped from a peak of 2% in March to be consistently below 1% since May 2020. Globally, case fatality rates have been linked to the strains/clades of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a specific country. Here we present 46 whole genomes of SARS-CoV-2 circulating in Ghana, from two separate sequencing batches: 15 isolates from the early epidemic (March 12–April 1 2020) and 31 from later time-points ( 25–27 May 2020). Sequencing was carried out on an Illumina MiSeq system following an amplicon-based enrichment for SARS-CoV-2 cDNA. After genome assembly and quality control processes, phylogenetic analysis showed that the first batch of 15 genomes clustered into five clades: 19A, 19B, 20A, 20B, and 20C, whereas the second batch of 31 genomes clustered to only three clades 19B, 20A, and 20B. The imported cases (6/46) mapped to circulating viruses in their countries of origin, namely, India, Hungary, Norway, the United Kingdom, and the United States of America. All genomes mapped to the original Wuhan strain with high similarity (99.5–99.8%). All imported strains mapped to the European superclade A, whereas 5/9 locally infected individuals harbored the B4 clade, from the East Asian superclade B. Ghana appears to have 19B and 20B as the two largest circulating clades based on our sequence analyses. In line with global reports, the D614G linked viruses seem to be predominating. Comparison of Ghanaian SARS-CoV-2 genomes with global genomes indicates that Ghanaian strains have not diverged significantly from circulating strains commonly imported into Africa. The low level of diversity in our genomes may indicate lower levels of transmission, even for D614G viruses, which is consistent with the relatively low levels of infection reported in Ghana.  相似文献   

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Antiphospholipid antibodies (aPLs), present in 1–5 % of healthy individuals, are associated with the risk of antiphospholipid syndrome (APS), which is the most common form of acquired thrombophilia. APLs may appear following infections or vaccinations and have been reported in patients with COronaVIrus Disease-2019 (COVID-19). However, their association with COVID-19 vaccination is unclear. Notably, a few cases of thrombocytopenia and thrombotic events resembling APS have been reported to develop in recipients of either adenoviral vector- or mRNA-based COVID-19 vaccines.The aim of this review is therefore to speculate on the plausible role of aPLs in the pathogenesis of these rare adverse events.Adenoviral vector-based vaccines can bind platelets and induce their destruction in the reticuloendothelial organs. Liposomal mRNA-based vaccines may instead favour activation of coagulation factors and confer a pro-thrombotic phenotype to endothelial cells and platelets. Furthermore, both formulations may trigger a type I interferon response associated with the generation of aPLs. In turn, aPLs may lead to aberrant activation of the immune response with participation of innate immune cells, cytokines and the complement cascade. NETosis, monocyte recruitment and cytokine release may further support endothelial dysfunction and promote platelet aggregation. These considerations suggest that aPLs may represent a risk factor for thrombotic events following COVID-19 vaccination, and deserve further investigations.  相似文献   

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ADAM23 (a disintegrin and metalloprotease 23), a member of brain MDC (macrophage‐derived chemokine) family, is important for the development of CNS (central nervous system). P19 mouse embryonal carcinoma cells can differentiate into neurons when cultured in aggregates and induced with RA (retinoic acid). We have found that under conditions without RA induction, knocking down ADAM23 with RNAi (RNA interference) promoted neuronal differentiation, and similarly recombinant GST (glutathione transferase)‐ADAM23‐DIS protein inhibited neuronal differentiation of P19/ADAM23KD (P19/ADAM23‐knockdown) cells. In P19/ADAM23KD, there were more cells arrested in G1 phase than normal P19 cells, due to the up‐regulation of P57KIP2 and P27KIP1 expression. P27KIP1 was up‐regulated during the differentiation process of both P19/ADAM23KD cells without RA induction, and P19 cells with RA induction. Transient overexpression of P27KIP1 in P19 cells also promoted neuronal differentiation of P19 cells. The findings indicate that ADAM23 suppresses neuronal differentiation through its disintegrin domain, and Adam23 KD up‐regulates P27KIP1 in P19/ADAM23KD cells, one reason that P19/ADAM23KD cells can differentiate into neurons without RA induction.  相似文献   

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Available COVID-19 data shows higher shares of cases and deaths occur among Black Americans, but reporting of data by race is poor. This paper investigates disparities in county-level mortality rates across counties with higher and lower than national average Black population shares using nonlinear regression decomposition and estimates potential differential impact of social distancing measures. I find counties with Black population shares above the national share have mortality rates 2 to 3 times higher than in other counties. Observable differences in living conditions, health, and work characteristics reduce the disparity to approximately 1.25 to 1.65 overall, and explain 100% of the disparity at 21 days after the first case. Though higher rates of comorbidities in counties with higher Black population shares are an important predictor, living situation factors like single parenthood and population density are just as important. Higher rates of co-residence with grandchildren explain 11% of the 21 day disparity but do not appear important by 42 days, suggesting families may have been better able to protect vulnerable family members later in the epidemic. To analyze differential effects of social distancing measures use two approaches. First, I exploit the timing of interventions relative to the first case among counties that began their epidemic at the same time. Second, I use event study analysis to analyze within-county changes in mortality. Findings for social distancing measures are not always consistent across approaches. Overall, I find no evidence that school closures were less effective in counties with larger Black population shares, and some estimates suggest closures may have disproportionately helped more diverse counties and counties with high rates of grandparent and grandchild co-residence. Conversely, stay at home orders are less clearly associated with mortality in any counties, reaching peak unemployment did not reduce mortality in any models, and some estimates indicate reaching peak unemployment before the first case was associated with higher mortality rates, especially in more diverse counties.  相似文献   

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Cell destruction results in plasma accumulation of cell-free DNA (cfDNA). Dynamic changes in circulating lymphocytes are features of COVID-19. We aimed to investigate if cfDNA level can serve in stratification of COVID-19 patients, and if cfDNA level is associated with alterations in lymphocyte subsets and neutrophil-to-lymphocyte ratio (NLR). This cross-sectional comparative study enrolled 64 SARS-CoV-2-positive patients. Patients were subdivided to severe and non-severe groups. Plasma cfDNA concentration was determined by real-time quantitative PCR. Lymphocyte subsets were assessed by flow cytometry. There was significant increase in cfDNA among severe cases when compared with non-severe cases. cfDNA showed positive correlation with NLR and inverse correlation with T cell percentage. cfDNA positively correlated with ferritin and C-reactive protein. The output data of performed ROC curves to differentiate severe from non-severe cases revealed that cfDNA at cut-off ≥17.31 ng/µl and AUC of 0.96 yielded (93%) sensitivity and (73%) specificity. In summary, excessive release of cfDNA can serve as sensitive COVID-19 severity predictor. There is an association between cfDNA up-regulation and NLR up-regulation and T cell percentage down-regulation. cfDNA level can be used in stratification and personalized monitoring strategies in COVID-19 patients.  相似文献   

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Heme-oxygenase 1 (HO-1) is an enzyme with well-known anti-inflammatory and antioxidant properties, whose levels have been previously associated with disease severity in the context of sterile and infectious diseases. Moreover, the heme/HO-1 pathway has been associated with prothrombotic changes in other diseases. Accordingly, the potential of modulating HO-1 levels for the treatment of COVID-19 was extensively speculated during the COVID-19 pandemic, but very few actual data were generated. The aim of our study was to explore the association of HO-1, heme, and hemopexin (HPX) levels with COVID-19 severity and with markers of inflammation and coagulation activation. The study was conducted in 30 consecutive patients with COVID-19 admitted due to hypoxemia, and 30 healthy volunteers matched by sex, age, and geographic region. HO-1 and HPX levels were measured by enzyme immunoassay (ELISA) and heme levels were measured by a colorimetric method. A comprehensive panel of coagulation and fibrinolysis activation was also used. Patients with COVID-19 presented increased levels of HO-1 when compared to controls (5741 ± 2696 vs 1953 ± 612 pg/mL, respectively, P < 0.0001), as well as a trend toward increased levels of HPX (3.724 ± 0.880 vs 3.254 ± 1.022 mg/mL, respectively; P = 0.06). In addition, HO-1 and HPX levels reduced from admission to day + 4. HO-1 levels were associated with duration of intensive care unit stay and with several markers of coagulation activation. In conclusion, modulation of HO-1 could be associated with the prothrombotic state observed in COVID-19, and HO-1 could also represent a relevant biomarker for COVID-19. New independent studies are warranted to explore and expand these findings.  相似文献   

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The SARS-CoV-2 spike is the primary target of virus-neutralizing antibodies and critical to the development of effective vaccines against COVID-19. Here, we demonstrate that the prefusion-stabilized two-proline “S2P” spike—widely employed for laboratory work and clinical studies—unfolds when stored at 4 °C, physiological pH, as observed by electron microscopy (EM) and differential scanning calorimetry, but that its trimeric, native-like conformation can be reacquired by low pH treatment. When stored for approximately 1 week, this unfolding does not significantly alter antigenic characteristics; however, longer storage diminishes antibody binding, and month-old spike elicits virtually no neutralization in mice despite inducing high ELISA-binding titers. Cryo-EM structures reveal the folded fraction of spike to decrease with aging; however, its structure remains largely similar, although with varying mobility of the receptor-binding domain. Thus, the SARS-CoV-2 spike is susceptible to unfolding, which affects immunogenicity, highlighting the need to monitor its integrity.  相似文献   

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Due to the essential role of dentists in stopping the COVID-19 pandemic, the purpose of this review is to help dentists to detect any weaknesses in their disinfection and cross-contamination prevention protocols, and to triage dental treatments to meet the needs of patients during the pandemic. We used PRISMA to identify peer-reviewed publications which supplemented guidance from the center for disease control about infection control and guidelines for dentists. Dentists must triage dental treatments to meet the needs of patients during the pandemic. The ongoing pandemic has changed the practice of dentistry forever, the changes make it more cumbersome, time-consuming, and costly due to the possible pathways of transmission and mitigation steps needed to prevent the spread of COVID-19. Dental chairside rapid tests for SARS-CoV-2 are urgently needed. Until then, dentists need to screen patients for COVID-19 even though 75% of people with COVID-19 have no symptoms. Despite the widespread anxiety and fear of the devastating health effects of COVID-19, only 61% of dentists have implemented a change to their treatment protocols. As an urgent matter of public health, all dentists must identify the additional steps they can take to prevent the spread of COVID-19. The most effective steps to stop the pandemic in dental offices are to; vaccinate all dentists, staff, and patients; triage dental treatments for patients, separate vulnerable patients, separate COVID-19 patients, prevent cross-contamination, disinfect areas touched by patients, maintain social distancing, and change personal protective equipment between patients.  相似文献   

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《Cell host & microbe》2022,30(8):1093-1102.e3
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《Cell》2022,185(12):2103-2115.e19
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Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662–C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662–C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662–C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.  相似文献   

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Background: Macau is a densely populated international tourist city. Compared to most tensely populated countries/territories, the prevalence and mortality of COVID-19 in Macau are lower. The experiences in Macau could be helpful for other areas to combat the COVID-19 pandemic. This article introduced the endeavours and achievements of Macau in combatting the COVID-19 pandemic.Method: Both qualitative and quantitative analysis methods were used to explore the work, measures, and achievements of Macau in dealing with the COVID-19 pandemic.Results: The results revealed that Macau has provided undifferentiated mask purchase reservation services, COVID-19 vaccination services to all residents and non-residents in Macau along with delivering multilingual services, in Chinese, English and Portuguese, to different groups of the population. To facilitate the travels of people, business and trades between Macau and mainland China, the Macau government launched the Macau Health Code System, which uses the health status declaration, residence history declaration, contact history declaration of the declarant to match various relevant backend databases within the health authority and provide a risk-related colour code operations. The Macau Health Code System connects to the Chinese mainland''s own propriety health code system seamlessly, whilst effectively protecting the privacy of the residents. Macau has also developed the COVID-19 Vaccination Appointment system, the Nucleic Acid Test Appointment system, the Port and Entry/Exit Quarantine system, the medical and other supporting systems.Conclusion: The efforts in Macau have achieved remarkable results in COVID-19 prevention and control, effectively safeguarding the lives and health of the people and manifesting the core principle of “serving the public”. The measures used are sustainable and can serve as an important reference for other countries/regions.  相似文献   

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BackgroundThe administration of radiotherapy should be encouraged despite the emergency of COVID-19; therefore, our aim is to analyze management and therapeutic interventions to be implemented in a Radiotherapy department to allow patients to continue their treatment and health professionals to continue their work safely.Materials and methodsA Pubmed search was performed, in which all articles specific to Radiotherapy and COVID-19 were included. Those articles that were too specific about the COVID-19, surgery and chemiotherapy, were excluded.Results315 articles were selected, of which 35 were about therapeutic strategies and 25 about management strategies. In the first category, 5 articles were about how radiotherapy could be a weapon to be used for COVID-19 positive patients with important lung problems. While 30 articles described priorities and new treatment plans for oncology patients who have to undergo radiotherapy during the pandemic. In the second category, almost all the articles explained how triage can be a preventive and monitoring way against COVID-19 in an operating unit with many patients and professionals, and other articles developed a telemedicine system, too, which allows patients to make scheduled visits without coming to the hospital and also for the staff, who can work remotely. In addition, 5 articles concerning psychological aspects of both patients and health care providers were included.ConclusionThis document can be used as a summary in the coming months/years, during the recovery phase from COVID-19 pandemic outbreak and as a starting point to be used in case of further pandemic break-out.  相似文献   

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Background: In 2019, the coronavirus pandemic emerged, resulting in the highest mortality and morbidity rate globally. It has a prevailing transmission rate and continues to be a global burden. There is a paucity of data regarding the role of long non-coding RNAs (lncRNAs) in COVID-19. Therefore, the current study aimed to investigate lncRNAs, particularly NEAT1 and TUG1, and their association with IL-6, CCL2, and TNF-α in COVID-19 patients with moderate and severe disease.Methods: The study was conducted on 80 COVID-19 patients (35 with severe and 45 with moderate infection) and 40 control subjects. Complete blood count (CBC), D-dimer assay, serum ferritin, and CRP were assayed. qRT-PCR was used to measure RNAs and lncRNAs.Results: NEAT1 and TUG1 expression levels were higher in COVID-19 patients compared with controls (P<0.001). Furthermore, CCL2, IL-6, and TNF-α expressions were higher in COVID-19 patients compared to controls (P<0.001). CCL2 and IL-6 expression levels were significantly higher in patients with severe compared to those with moderate COVID-19 infection (P<0.001). IL-6 had the highest accuracy in distinguishing COVID-19 patients (AUC=1, P<0.001 at a cutoff of 0.359), followed by TUG1 (AUC=0.999, P<0.001 at a cutoff of 2.28). NEAT1 and TUG1 had significant correlations with the measured cytokines, and based on the multivariate regression analysis, NEAT1 is the independent predictor for survival in COVID-19 patients (P=0.02).Conclusion: In COVID-19 patients, significant overexpression of NEAT1 and TUG1 was observed, consistent with cytokine storm. TUG1 could be an efficient diagnostic biomarker, whereas NEAT1 was an independent predictor for overall survival.  相似文献   

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During the COVID-19 pandemic, both the U.S. and Europe have issued movement restrictions with the exception of visits to essential services, including groceries and pharmacies. Using Google's data on community mobility, I employ an event-study design to compare the effects of movement restrictions on physical mobility in the U.S. and Europe. I find that compared to Europe, the U.S. has higher levels of mobility related to visits to groceries and pharmacies and lower levels of the residential presence relative to baseline values, and the differences are not only statistically significant but also of large magnitudes. Such differences in post-restriction mobility are still significant between Europe and the U.S.’ early epicenters of COVID-19. The main results of this paper are robust to changes in samples and specifications. These findings suggest that movement restrictions appear to be less effective in the U.S., which have useful implications for health policy evaluation, pandemic forecasting, and economic recovery.  相似文献   

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The Envelope (E) protein of SARS-CoV-2 is the most enigmatic protein among the four structural ones. Most of its current knowledge is based on the direct comparison to the SARS E protein, initially mistakenly undervalued and subsequently proved to be a key factor in the ER-Golgi localization and in tight junction disruption.We compared the genomic sequences of E protein of SARS-CoV-2, SARS-CoV and the closely related genomes of bats and pangolins obtained from the GISAID and GenBank databases. When compared to the known SARS E protein, we observed a significant difference in amino acid sequence in the C-terminal end of SARS-CoV-2 E protein.Subsequently, in silico modelling analyses of E proteins conformation and docking provide evidences of a strengthened binding of SARS-CoV-2 E protein with the tight junction-associated PALS1 protein. Based on our computational evidences and on data related to SARS-CoV, we believe that SARS-CoV-2 E protein interferes more stably with PALS1 leading to an enhanced epithelial barrier disruption, amplifying the inflammatory processes, and promoting tissue remodelling. These findings raise a warning on the underestimated role of the E protein in the pathogenic mechanism and open the route to detailed experimental investigations.  相似文献   

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