Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 105
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
J Biol Chem ; 299(12): 105362, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37863261

RESUMO

The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein serine/arginine (SR) region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N∗ or Δ(1-209), that mediates genome packaging despite lacking the N-terminal RNA-binding domain and SR region. Here, we use mass photometry and negative stain electron microscopy to show that purified Δ(1-209) and viral RNA assemble into vRNPs that are remarkably similar in size and shape to those formed with full-length N protein. We show that assembly of Δ(1-209) vRNPs requires the leucine-rich helix of the central disordered region and that this helix promotes N protein oligomerization. We also find that fusion of a phosphomimetic SR region to Δ(1-209) inhibits RNA binding and vRNP assembly. Our results provide new insights into the mechanisms by which RNA binding promotes N protein self-association and vRNP assembly, and how this process is modulated by phosphorylation.


Assuntos
Proteínas do Nucleocapsídeo , SARS-CoV-2 , Humanos , COVID-19/virologia , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo , Proteínas do Nucleocapsídeo/ultraestrutura , RNA Viral/metabolismo , RNA Viral/ultraestrutura , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/ultraestrutura , Fosforilação , Montagem de Vírus/genética
2.
J Med Virol ; 96(2): e29448, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38318776

RESUMO

The magnitude and breadth of the neutralizing antibody response against variants of concern following natural infection would provide valuable insights regarding the immune response induced by severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection. Herein, 25 patients were followed at 30 ±7 (Visit 1), 90± 15 (Visit 2), and 180 ± 15 (Visit 3) days post symptom onset (PSO). The neutralization titers against both Wuhan-Hu-1 (WT) and Delta variant were analyzed in parallel along with anti-Spike antibodies (anti-S1/S2 immunoglobulin G [IgG]). The median values of half-maximal neutralization titer (NT50 ) for the WT and Delta variants decreased by 75.8% and 82.2% at Visit 2 and by 85.4% and 81.4% at Visit 3, respectively. At Visit 1, the correlation between the anti-S1/S2 IgG and Nabs titers for the Delta variant was moderate for WT (r = 0.58) and weak for the Delta variant (r = 0.39). However, the correlation coefficient consistently remained above 0.7, with a very strong correlation at Visit 3 for both WT and Delta variants (r = 0.81). The dynamics of anti-S1/S2 IgG antibodies, NT50 , and cross-neutralization index correlated at different time points PSO. Longitudinal analysis of the cross-neutralization capacity of immune sera will inform upon the durability of the immune response against SARS CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Anticorpos Neutralizantes , Imunoglobulina G , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus/genética
3.
Bull Math Biol ; 86(3): 31, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353870

RESUMO

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. Estimated takeoff times are consistent with genomic surveillance data.


Assuntos
COVID-19 , SARS-CoV-2 , Estados Unidos/epidemiologia , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/prevenção & controle , Conceitos Matemáticos , Modelos Biológicos , Vacinação
4.
Emerg Infect Dis ; 29(10): 1999-2007, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37640374

RESUMO

In British Columbia, Canada, initial growth of the SARS-CoV-2 Delta variant was slower than that reported in other jurisdictions. Delta became the dominant variant (>50% prevalence) within ≈7-13 weeks of first detection in regions within the United Kingdom and United States. In British Columbia, it remained at <10% of weekly incident COVID-19 cases for 13 weeks after first detection on March 21, 2021, eventually reaching dominance after 17 weeks. We describe the growth of Delta variant cases in British Columbia during March 1-June 30, 2021, and apply retrospective counterfactual modeling to examine factors for the initially low COVID-19 case rate after Delta introduction, such as vaccination coverage and nonpharmaceutical interventions. Growth of COVID-19 cases in the first 3 months after Delta emergence was likely limited in British Columbia because additional nonpharmaceutical interventions were implemented to reduce levels of contact at the end of March 2021, soon after variant emergence.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Colúmbia Britânica/epidemiologia , SARS-CoV-2/genética , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle
5.
Am J Epidemiol ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37981717

RESUMO

Post-acute symptoms are not uncommon after SARS-CoV-2 infection with pre-Omicron variants. How Omicron and COVID-19 booster vaccination influence the risk of post-acute symptoms is less clear. We analyzed data from the nationwide Danish questionnaire study EFTER-COVID comprising 44,553 individuals ≥15 years old, tested between July 2021 and January 2022, in order to evaluate the association of the Omicron variant and COVID-19 booster vaccination with post-acute symptoms and new-onset general health problems, four months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron -cases to controls, Omicron to Delta -cases, and Omicron vaccinated cases with three to -two doses, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial post-acute symptoms and new-onset health problems compared to controls; the largest RD was observed for memory issues (RD=7.2%, 95%CI: 6.4 to 8.1). However, risks were generally lower than in the Delta period, particularly for dysosmia (RD=-15.0%, 95%CI: -17.0 to -13.2) and dysgeusia (RD=-11.2%, 95%CI: -13.2 to -9.5). Booster vaccination was associated with fewer post-acute symptoms and new-onset health problems, four months after Omicron infection, compared to two COVID-19 vaccine doses.

6.
J Med Virol ; 95(2): e28461, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36602045

RESUMO

One of the most consequential unknowns of the COVID-19 pandemic is the frequency at which vaccine boosting provides sufficient protection from infection. We quantified the statistical likelihood of breakthrough infections over time following different boosting schedules with messenger RNA (mRNA)-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech). We integrated anti-Spike IgG antibody optical densities with profiles of the waning of antibodies and corresponding probabilities of infection associated with coronavirus endemic transmission. Projecting antibody levels over time given boosting every 6 months, 1, 1.5, 2, or 3 years yielded respective probabilities of fending off infection over a 6-year span of >93%, 75%, 55%, 40%, and 24% (mRNA-1273) and >89%, 69%, 49%, 36%, and 23% (BNT162b2). Delaying the administration of updated boosters has bleak repercussions. It increases the probability of individual infection by SARS-CoV-2, and correspondingly, ongoing disease spread, prevalence, morbidity, hospitalization, and mortality. Instituting regular, population-wide booster vaccination updated to predominant variants has the potential to substantially forestall-and with global, widespread uptake, eliminate-COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Vacina BNT162 , Pandemias , Anticorpos Antivirais , Vacinas de mRNA
7.
Med Microbiol Immunol ; 212(1): 25-34, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36370196

RESUMO

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein.


Assuntos
COVID-19 , SARS-CoV-2 , Masculino , Humanos , Feminino , SARS-CoV-2/genética , Anticorpos Neutralizantes , Anticorpos Antivirais
8.
BMC Infect Dis ; 23(1): 264, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37101288

RESUMO

OBJECTIVES: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during the Omicron variant outbreak. METHODS: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, and household vaccination rates were collected through electronic health records and telephone interviews. RESULTS: A total of 603 paediatric patients confirmed to have COVID-19 were included in this study. Both univariate and multivariate analyses were performed to filter independent factors for the duration to viral RNA negative conversion. Data on the redetection of SARS-CoV-2 in the patients after they showed negative results on the RT‒PCR test (intermittent negative status) were also analysed. The median duration of virus shedding was 12 (interquartile range, IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, and abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patients who had abnormal defecation or with more severe conditions would have delayed virological clearance, while patients who previously had 2 doses of vaccination or had higher household vaccination rates would have accelerated virological clearance. Loss of appetite (odds ratio (OR): 5.343; 95% CI: 3.307-8.632) and abnormal defecation (OR: 2.840; 95% CI: 1.736-4.645) were significantly associated with intermittent negative status. CONCLUSION: These findings could provide clues for the early identification of paediatric patients with prolonged viral shedding and could enrich the evidence for the development of prevention and control strategies, especially vaccination policies for children and adolescents.


Assuntos
COVID-19 , Dispepsia , Adolescente , Humanos , Criança , Criança Hospitalizada , RNA Viral/genética , SARS-CoV-2/genética , Estudos Retrospectivos , China/epidemiologia , COVID-19/epidemiologia
9.
Mol Ther ; 30(5): 1979-1993, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35167974

RESUMO

As of December 2021, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single-chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the Delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Because of their high efficiency, remarkable stability, resilience to nebulization, and low cost of production, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Humanos , Fragmentos de Imunoglobulinas , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus
10.
BMC Pediatr ; 23(1): 491, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770841

RESUMO

BACKGROUND: As the coronavirus disease-2019 (COVID-19) pandemic continues, driven by the Omicron variant, infection rates in children have recently rapidly surged compared with previous years. We aimed to investigate the presentation of kidney involvement in children after Omicron variant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. METHODS: We retrospectively reviewed the medical records of pediatric patients who presented with kidney disease with a temporal relationship with COVID-19 between January and August 2022 in a single tertiary center in Korea. RESULTS: Fifteen children presented with kidney involvement after Omicron variant infection, with a median age of 10.6 (6.8-18.3) years. None of the patients exhibited severe respiratory symptoms apart from cough and sore throat. The median time from infection to renal symptom onset was 3 (0-49) days. Among 10 patients with underlying kidney disease, six had previously been diagnosed with nephrotic syndrome (NS) that relapsed after COVID-19 infection, two with immunoglobulin A nephropathy (IgAN) experienced transient gross hematuria (GHU) with or without acute kidney injury (AKI), and two with kidney transplantation presented with AKI. Of the five patients without underlying kidney disease, one patient had NS, and the other four patients had GHU and proteinuria (PU), of whom one was eventually diagnosed with Henoch Shönlein Purpura nephritis (HSPN), and one with rhabdomyolysis. The seven patients with NS (1 new-onset, 6 relapsed) had uneventful remission with corticosteroid therapy. Apart from one patient with new-onset HSPN, GHU and PU resolved spontaneously in all affected patients, and AKI also resolved with supportive care. CONCLUSIONS: Kidney involvement subsequent to Omicron variant COVID-19 exhibited various, but mostly mild manifestations in children.


Assuntos
Injúria Renal Aguda , COVID-19 , Vasculite por IgA , Nefrite , Síndrome Nefrótica , Humanos , Criança , Adolescente , SARS-CoV-2 , Pandemias , Estudos Retrospectivos , Rim , Proteinúria/etiologia , Vasculite por IgA/diagnóstico , Injúria Renal Aguda/etiologia , Hematúria/etiologia
11.
Clin Infect Dis ; 74(5): 821-828, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-34137815

RESUMO

BACKGROUND: Although mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines report >90% efficacy, breakthrough infections occur. Little is known about their effectiveness against SARS-CoV-2 variants, including the highly prevalent B.1.427/B.1.429 variant. METHODS: In this quality improvement project, we collected demographic and clinical information from post-vaccine SARS-CoV-2 cases (PVSCs), defined as healthcare personnel (HCP) with positive SARS-CoV-2 nucleic acid amplification test after receiving ≥1 vaccine dose. Available specimens were tested for L452R, N501Y, and E484K mutations using reverse-transcription polymerase chain reaction. Mutation prevalence was compared among unvaccinated, early post-vaccinated (≤14 days after dose 1), partially vaccinated (positive test >14 days after dose 1 and <14 days after dose 2), and fully vaccinated (>14 days after dose 2) PVSCs. RESULTS: From December 2020 to April 2021, ≥23 090 HCP received ≥1 dose of an mRNA-based SARS-CoV-2 vaccine, and 660 HCP cases of SARS-CoV-2 occurred, of which 189 were PVSCs. Among the PVSCs, 114 (60.3%), 49 (25.9%), and 26 (13.8%) were early post-vaccination, partially vaccinated, and fully vaccinated, respectively. Of 261 available samples from vaccinated and unvaccinated HCP, 103 (39.5%), including 42 PVSCs (36.5%), had the L452R mutation presumptive of B.1.427/B.1.429. When adjusted for community prevalence of B.1.427/B.1.429, PVSCs did not have significantly elevated risk of B.1.427/B.1.429 compared with unvaccinated HCP. CONCLUSIONS: Most PVSCs occurred prior to expected onset of full, vaccine-derived immunity. Presumptive B.1.427/B.1.429 was not more prevalent in post-vaccine cases than in unvaccinated SARS-CoV-2 HCP. Continued infection control measures, particularly <14 days post-vaccination, and continued variant surveillance in PVSCs are imperative to control future SARS-CoV-2 surges.


Assuntos
COVID-19 , SARS-CoV-2 , Centros Médicos Acadêmicos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Atenção à Saúde , Humanos , Incidência , SARS-CoV-2/genética , Vacinação
12.
BMC Genomics ; 23(1): 755, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36384483

RESUMO

BACKGROUND: Since inception of the COVID-19 pandemic, early detection and isolation of positive cases is one of the key strategies to restrict disease transmission. Real time reverse transcription polymerase chain reaction (qRTPCR) has been the mainstay of diagnosis. Most of the qRTPCR kits were designed against the target genes of original strain of SARS-CoV-2. However, with the emergence of variant strains of SARS-CoV-2, sensitivity of the qRTPCR assays has reportedly reduced. In view of this, it is critical to continuously monitor the performance of the qRTPCR kits in the backdrop of variant strains of SARS-CoV-2. Real world monitoring of assay performance is challenging. Therefore, we developed a two-step in-silico screening process for evaluating the performance of various qRTPCR kits used in India. RESULTS: We analysed 73 qRT-PCR kits marketed in India, against the two SARS-CoV-2 VoCs. Sequences of both Delta (B.1.617.2) and Omicron (B.1.1.529) VoCs submitted to GISAID within a specific timeframe were downloaded, clustered to identify unique sequences and aligned with primer and probe sequences. Results were analysed following a two-step screening process. Out of 73 kits analysed, seven were unsatisfactory for detection of both Delta and Omicron VoCs, 10 were unsatisfactory for Delta VoC whereas 2 were unsatisfactory for only Omicron VoC. CONCLUSION: Overall, we have developed a useful screening process for evaluating the performance of qRTPCR assays against Delta and Omicron VoCs of SARS-CoV-2 which can be used for detecting SARS-CoV-2 VoCs that may emerge in future and can also be redeployed for other evolving pathogens of public health importance.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias , RNA Viral/genética , RNA Viral/análise , Sensibilidade e Especificidade , COVID-19/diagnóstico , COVID-19/epidemiologia
13.
BMC Med ; 20(1): 451, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36419108

RESUMO

BACKGROUND: The Omicron variant (B.1.1.529) is estimated to be more transmissible than previous strains of SARS-CoV-2 especially among children, potentially resulting in croup which is a characteristic disease in children. Current coronavirus disease 2019 (COVID-19) cases among children might be higher because (i) school-aged children have higher contact rates and (ii) the COVID-19 vaccination strategy prioritizes the elderly in most countries. However, there have been no reports confirming the age-varying susceptibility to the Omicron variant to date. METHODS: We developed an age-structured compartmental model, combining age-specific contact matrix in South Korea and observed distribution of periods between each stage of infection in the national epidemiological investigation. A Bayesian inference method was used to estimate the age-specific force of infection and, accordingly, age-specific susceptibility, given epidemic data during the third (pre-Delta), fourth (Delta driven), and fifth (Omicron driven) waves in South Korea. As vaccine uptake increased, individuals who were vaccinated were excluded from the susceptible population in accordance with vaccine effectiveness against the Delta and Omicron variants, respectively. RESULTS: A significant difference between the age-specific susceptibility to the Omicron and that to the pre-Omicron variants was found in the younger age group. The rise in susceptibility to the Omicron/pre-Delta variant was highest in the 10-15 years age group (5.28 times [95% CI, 4.94-5.60]), and the rise in susceptibility to the Omicron/Delta variant was highest in the 15-19 years age group (3.21 times [95% CI, 3.12-3.31]), whereas in those aged 50 years or more, the susceptibility to the Omicron/pre-Omicron remained stable at approximately twofold. CONCLUSIONS: Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the Omicron variant of SARS-CoV-2 tends to propagate more easily among children than the pre-Omicron strains.


Assuntos
COVID-19 , Criança , Adolescente , Humanos , Idoso , Adulto Jovem , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teorema de Bayes , Vacinas contra COVID-19 , SARS-CoV-2/genética
14.
Virol J ; 19(1): 2, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983583

RESUMO

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Camundongos , SARS-CoV-2/imunologia
15.
BMC Infect Dis ; 22(1): 645, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35896965

RESUMO

BACKGROUND: Monoclonal antibodies (mAb) prevent COVID-19 progression when administered early. We compared mAb treatment outcomes among vaccinated and unvaccinated patients during Delta wave and assessed the feasibility of implementing stricter eligibility criteria in the event of mAb scarcity. METHODS: We conducted a retrospective observational study of casirivimab/imdevimab recipients with mild-to-moderate COVID-19 infection in an emergency department or outpatient infusion center (July 1-August 20, 2021). Primary outcome was all-cause hospital admission within 30 days post-treatment between vaccinated vs. unvaccinated patients during Delta surge in the Bronx, NY. RESULTS: A total of 250 patients received casirivimab/imdevimab (162 unvaccinated vs. 88 vaccinated). The median age was 39 years for unvaccinated patients, and 52 years for vaccinated patients (p < 0.0001). The median number of EUA criteria met was 1 for unvaccinated and 2 for vaccinated patients (p < 0.0001). Overall, 6% (15/250) of patients were admitted within 30 days post-treatment. Eleven unvaccinated patients (7%) were admitted within 30-days compared to 4 (5%) vaccinated patients (p = 0.48). CONCLUSIONS: All-cause 30-day admission was not statistically different between vaccinated and unvaccinated patients. When federal allocation of therapies is limited, programs must prioritize patients at highest risk of hospitalization and death regardless of vaccination status.


Assuntos
COVID-19 , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , COVID-19/prevenção & controle , Humanos , Estudos Retrospectivos
16.
J Korean Med Sci ; 37(3): e31, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35040299

RESUMO

Since severe acute respiratory syndrome-coronavirus-2 variant B.1.1.529 (omicron) was first reported to the World Health Organization on November 24, 2021, the cases of the omicron variant have been detected in more than 90 countries over the last month. We investigated the clinical and epidemiological characteristics of the first 40 patients with the omicron variant who had been isolated at the National Medical Center in South Korea during December 4-17, 2021. The median age of the patients was 39.5 years. Twenty-two patients (55%) were women. Seventeen patients (42.5%) were fully vaccinated, and none were reinfected with the omicron. Eighteen (45%) had recent international travel history. Half of the patients (19, 47.5%) were asymptomatic, while the others had mild symptoms. Six patients (15%) showed lung infiltrations on chest image; however, none required supplemental oxygen. These mild clinical features are consistent with recent case reports on the omicron variant from other countries.


Assuntos
COVID-19/epidemiologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/patologia , Testes Diagnósticos de Rotina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , SARS-CoV-2/genética , Viagem , Doença Relacionada a Viagens , Adulto Jovem
17.
Euro Surveill ; 27(5)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35115077

RESUMO

BackgroundSeveral SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.MethodsWe conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.ResultsThe Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.ConclusionWe assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Itália/epidemiologia , Modelos Teóricos
18.
Chaos Solitons Fractals ; 157: 111954, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35250194

RESUMO

In this study, a new approach to COVID-19 pandemic is presented. In this context, a fractional order pandemic model is developed to examine the spread of COVID-19 with and without Omicron variant and its relationship with heart attack using real data from the United Kingdom. In the model, heart attack is adopted by considering its relationship with the quarantine strategy. Then, the existence, uniqueness, positivity and boundedness of the solution are studied. The equilibrium points and their stability conditions are achieved. Subsequently, we calculate the basic reproduction number (the virus transmission coefficient) that simply refers to the number of people, to whom an infected person can make infected, as R 0 = 3.6456 by using the next generation matrix method. Next, we consider the sensitivity analysis of the parameters according to R 0 . In order to determine the values of the parameters in the model, the least squares curve fitting method, which is one of the leading methods in parameter estimation, is benefited. A total of 21 parameter values in the model are estimated by using real Omicron data from the United Kingdom. Moreover, in order to highlight the advantages of using fractional differential equations, applications related to memory trace and hereditary properties are given. Finally, the numerical simulations are presented to examine the dynamic behavior of the system. As a result of numerical simulations, an increase in the number of people who have heart attacks is observed when Omicron cases were first seen. In the future, it is estimated that the risk of heart attack will decrease as the cases of Omicron decrease.

19.
Arch Pharm (Weinheim) ; 355(5): e2100382, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35040187

RESUMO

The outbreak of the coronavirus pandemic COVID-19 created by its severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variant, known for producing a very severe acute respiratory syndrome, has created an unprecedented situation by its continual assault around the world. The crisis caused by the SARS-CoV-2 variant has been a global challenge, calling to mitigate this unprecedented pandemic that has engulfed the whole world. Since the outbreak and spread of COVID-19, many researchers globally have been grappling to find new clinically trialed active drugs with anti-COVID-19 activity, from antimalarial drugs to JAK inhibitors, antiviral drugs, immune suppressants, and so forth. This article presents a brief discussion on the activity and synthesis of some active molecules such as favipiravir, hydroxychloroquine, pirfenidone, remdesivir, lopinavir, camostat, chloroquine, baricitinib, molnupiravir, and so forth, which are under trial.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Pandemias , Relação Estrutura-Atividade
20.
Int J Mol Sci ; 23(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35328562

RESUMO

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.


Assuntos
COVID-19/diagnóstico , Análise Mutacional de DNA/métodos , Genoma Viral/genética , Mutação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pandemias/prevenção & controle , Reprodutibilidade dos Testes , SARS-CoV-2/fisiologia , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA