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1.
Cogent Medicine ; 8, 2021.
Article in English | EMBASE | ID: covidwho-1617067

ABSTRACT

Background: Vaccination against COVID-19 in pediatric age has been a hot topic recently. This study aimed to assess parents' intention to vaccinate their children against COVID-19 and identify which factors may influence this decision. Methods: An observational study was conducted between June and July 2021 by applying an anonymous questionnaire to a sample of caregivers of children and adolescents followed in ambulatory care in a Portuguese central hospital. We included sociodemographic data, immunization history, personal background, exposure to COVID-19 and caregivers' beliefs. At the time of the study, there was still no official recommendation from health authorities regarding vaccination in pediatric age. Results: A total of 78 questionnaires were conducted. The mean age of the children was 9.2 years (±5.9), 56.4% were male, 94.8% had an updated immunization history, and 65.8% had extra vaccines. Of these children, 22.1% had comorbidities. Among the caregivers, 83.3% were mothers, the mean age was 39.4 years (±9.4), and 26.9% had attended university. The vaccine was considered safe by 61.5%, and 34.6% answered they did not know whether to consider it safe or not. Information about the vaccine was obtained through television in 84.6%, social networks in 42.3% and 34.6% in the information given by health professionals. Regarding the intention to vaccinate their children, 76.9% answered "yes", 7.7% did not answer and 15.4% answered "no". The vaccine's ineffectiveness (n=5) and inappropriate age (n=3) were the most cited reasons not to vaccinate. In 82.9%, the number of doses of the vaccine would not influence the decision. Conclusions: The study results show that caregivers have considerable resistance to the vaccination of children and adolescents against COVID-19, mainly based on the belief in the vaccine's ineffectiveness. The majority obtained information about the vaccine in the media, which reinforces the importance and the opportunity for intervention by transmitting credible and perceptible information in these media.

2.
Blood ; 138:2164, 2021.
Article in English | EMBASE | ID: covidwho-1582247

ABSTRACT

Background: SARS-Cov-2 infections are associated with increased mortality and morbidity, largely due to inflammatory cascades and cytokine release syndrome (CRS). Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the presence and subsequent expansion of somatic, leukemia-associated driver mutations in apparently healthy individuals with normal blood counts. CHIP has been associated with increased inflammation, with cytokines such as IL1-b, IL6 and TNF-a being elevated at baseline in affected individuals. We hypothesized that the presence of CHIP in patients with COVID-19 would result in excessive inflammation-related mortality and morbidity. Methods: We used the Mayo Clinic COVID-19 database to identify patients with COVID-19 on whom peripheral blood mononuclear cells (PBMC) were available for research use (IRB approved). We carried out target-capture next generation sequencing for 220 CH related genes, by previously described methods (1000 x coverage, variant allele fraction/VAF detection limit >0.5%;Kusne Y et al AJH 2021). CHIP was defined by the presence of a CH mutation with a VAF>1% in an individual with normal baseline blood counts. Demographics, blood counts, and inflammatory markers (CRP and cytokine levels- ELISA assay) at COVID-19 diagnosis and during follow-up (as clinically indicated) were collected. COVID-19 disease severity was classified based on the presence and severity of CRS, graded using the Penn Grading Scale (Porter et. al., 2018), and the WHO ordinal scale (WHO Blueprint, 2020). We used Fisher's exact test and the Wilcoxon rank sum test to compare categorical and continuous variables. Survival analysis was performed using the Kaplan-Meier method. We accounted for differences in age and sex using multivariable-adjusted proportional hazards regression models. Results: Seventy-two CHIP mutations were detected in 56 (25%) of the 227 patients with COVID-19 that had PBMC available;median age 69 years (range;42-99 years), 61% male. Fifteen (26%) patients had 2 CHIP mutations, while 1 patient had 3 CHIP mutations. Common mutations encountered included DNMT3A (32%), TET2 (19%), SF3B1 (8%), ASXL1 (6%), MPL (5%), and TP53 (5%;Figure 1A). COVID-19 patients with CHIP were older in age (median 69 vs 57 years;p<0.0001) and had higher baseline MCP-1 (p=0.04) levels. However, there were no differences in sex, comorbidities, blood counts, IL1-b, IL6 and TNF-a levels between the two groups. The median follow-up for the entire cohort was 9 months. The relative change from baseline in blood counts and inflammatory markers (CRP and cytokines) during follow-up was similar in CHIP and non-CHIP patients, with the exception that COVID-19-onset neutropenia was more common in CHIP patients (8% vs 1%;p=0.017) compared to those without CHIP. At last follow up neutropenia had resolved in all patients. Both groups had comparable number of patients with CRS (61% CHIP vs 53% non-CHIP patients, p=0.354, Figure 1B), however, CHIP patients had more severe CRS (median Penn Grade 3 versus 2 in non-CHIP, p=0.018, Figure 1C). Based on the WHO ordinal scale, CHIP patients were more likely to experience hospitalization with severe disease and death (61% versus 45% in non-CHIP, p = 0.049). Moreover, COVID-19 CHIP patients experienced worse overall survival in comparison to patients without CHIP (median 13.1 months vs not reached, p<0.001, Figure 1D). This association remained consistent after adjusting for age and sex at the time of COVID-19 diagnosis (HR 3.15, 95% 1.32 - 7.55, p = 0.010). At last follow-up, 22 deaths were documented: 13 (23%) in patients with CHIP and 9 (5%) in the non-CHIP group (p=0.02), with the primary cause for mortality being hypoxic respiratory failure (62% in CHIP vs 44% non-CHIP, p=0.04). Conclusions: In this study, we observe an age-independent impact of CHIP on COVID-19 associated inflammatory morbidity (CRS) and mortality (hypoxemic respiratory failure). We are currently carrying out detailed single cell (ssDNA, RNA and ATAC-seq) and proteomic studies (O-link PEA assays) to better elucidate this pathophysiology. [Formula presented] Disclosures: Patnaik: Kura Oncology: Research Funding;StemLine: Research Funding.

3.
Estudos Ibero-Americanos ; 47(3):9, 2021.
Article in Portuguese | Web of Science | ID: covidwho-1551931

ABSTRACT

The years 2020 and 2021 brought significant changes to our lives. New habits were introduced in everyday life from the need for social isolation and the way we face death was also radically affected. The article seeks to reflect on the fundamental role of the historian in recording the pandemic, based on the presentation of four works produced in this period that directly related the archive, memory, and the Covid-19 pandemic. The debate revolves around the possibility of reflecting on the "duty of memory" and the production of documents that may, in the future, help us understand how Brazil reached the level of more than half a million deaths from the disease in so little. time.

4.
PLoS ONE ; 16(2), 2021.
Article in English | CAB Abstracts | ID: covidwho-1410659

ABSTRACT

We analyze the trade-offs between health and the economy during the period of social distancing in Sao Paulo, the state hardest hit by the COVID-19 pandemic in Brazil. We use longitudinal data with municipal-level information and check the robustness of our estimates to several sources of bias, including spatial dependence, reverse causality, and time-variant omitted variables. We use exogenous climate shocks as instruments for social distancing since people are more likely to stay home in wetter and colder periods. Our findings suggest that the health benefits of social distancing differ by levels of municipal development and may have vanished if the COVID-19 spread was not controlled in neighboring municipalities. In turn, we did not find evidence that municipalities with tougher social distancing performed worse economically. Our results also highlight that estimates that do not account for endogeneity may largely underestimate the benefits of social distancing on reducing the spread of COVID-19.

5.
Sci Transl Med ; 13(593)2021 05 12.
Article in English | MEDLINE | ID: covidwho-1255516

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin-converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days and a clearance of 0.22 ml hour-1 kg-1, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study day 6 after viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral/immunology , COVID-19 , Animals , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/prevention & control , Macaca mulatta , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
7.
Clin Infect Dis ; 72(9): e334-e342, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1216627

ABSTRACT

BACKGROUND: One hundred days after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Vietnam on 23 January, 270 cases were confirmed, with no deaths. We describe the control measures used by the government and their relationship with imported and domestically acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control. METHODS: Clinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of government control measures, including numbers of tests and quarantined individuals, were analyzed. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of presymptomatic transmission events and time-varying reproduction numbers. RESULTS: A national lockdown was implemented between 1 and 22 April. Around 200 000 people were quarantined and 266 122 reverse transcription polymerase chain reaction (RT-PCR) tests conducted. Population mobility decreased progressively before lockdown. In total, 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. The serial interval was 3.24 days, and 27.5% (95% confidence interval [CI], 15.7%-40.0%) of transmissions occurred presymptomatically. Limited transmission amounted to a maximum reproduction number of 1.15 (95% CI, .·37-2.·36). No community transmission has been detected since 15 April. CONCLUSIONS: Vietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial presymptomatic transmission.


Subject(s)
COVID-19 , SARS-CoV-2 , Communicable Disease Control , Humans , Quarantine , Vietnam/epidemiology
8.
International Journal of Environmental Research & Public Health [Electronic Resource] ; 18(9):27, 2021.
Article in English | MEDLINE | ID: covidwho-1209831

ABSTRACT

The COVID-19 pandemic has important consequences for the mental health of populations. Patients with cancer, already at risk for poor mental health outcomes, are not expected to be spared from these consequences, prompting the need for health services to improve responsiveness. This article presents the research protocol for an implementation study designed to describe the uptake of a well-studied and recognized system for the treatment of depression and anxiety (Stepped-care) during the specific context of a Pandemic in an oncological site. The system set-up will be assisted by a digital platform (MoodUP), where patients undergoing cancer treatment will be screened for anxiety and depressive symptoms, triaged by severity level and algorithm-matched to recommended interventions. Patients undergoing cancer treatment at a cancer clinic in Portugal will be invited to subscribe to the MoodUP platform where they will complete a self-reported questionnaire (Hospital Anxiety and Depression Scale) to screen their anxiety and depressive symptoms. Data will be instantly collected, and an algorithm will activate severity-matched intervention suggestions, through a case manager that will coordinate care. The specific objectives of this study will be to describe the implementation and acceptability of the care system by patients and staff, the barriers to and facilitators of implementation, the proportion of patients accessing the system and their pathways through the various stepped-care interventions, and patient perceptions regarding the feasibility and appropriateness of the eHealth platform. Moreover, exploratory analyses will be conducted to describe patterns of anxiety and depression symptoms variation across all patients, as well as within sociodemographically, clinically and contextually characterized subgroups, to characterize their care needs and access, as well as to explore for whom the MoodUP care system may be more appropriate. This study is expected to improve processes for collaborative mental healthcare in oncology and accelerate the digitalization of services, towards the improvement of mental healthcare access, and management of high-risk patients, during the COVID-19 pandemic.

9.
Preprint in English | bioRxiv | ID: ppbiorxiv-442182

ABSTRACT

SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab). LY-CoV1404 potently neutralizes authentic SARS-CoV-2 virus, including the prototype, B.1.1.7, B.1.351 and B.1.617.2). In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, and B.1.1.529, and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis demonstrates that RBD residues comprising the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19. In BriefLY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated. HighlightsO_LILY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and known variants of concern including the B.1.1.529 (Omicron) and B.1.617.2 (Delta) variants C_LIO_LINo loss of potency against currently circulating variants C_LIO_LIBinding epitope on RBD of SARS-CoV-2 is rarely mutated in GISAID database C_LIO_LIBreadth of neutralizing activity and potency supports clinical development C_LI

10.
Sci Transl Med ; 13(593)2021 05 12.
Article in English | MEDLINE | ID: covidwho-1169861

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin-converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days and a clearance of 0.22 ml hour-1 kg-1, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study day 6 after viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral/immunology , COVID-19 , Animals , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/prevention & control , Macaca mulatta , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
11.
Emerg Infect Dis ; 27(5): 1519-1521, 2021 May.
Article in English | MEDLINE | ID: covidwho-1110222

ABSTRACT

A cluster of severe acute respiratory syndrome coronavirus 2 infections in Danang, Vietnam, began July 25, 2020, and resulted in 551 confirmed cases and 35 deaths as of February 2021. We analyzed 26 sequences from this cluster and identified a novel shared mutation in nonstructural protein 9, suggesting a single introduction into Vietnam.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation , RNA-Binding Proteins , Vietnam/epidemiology , Viral Proteins
14.
bioRxiv ; 2020 Oct 09.
Article in English | MEDLINE | ID: covidwho-835246

ABSTRACT

SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection. One Sentence Summary: LY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.

15.
Preprint in English | bioRxiv | ID: ppbiorxiv-318972

ABSTRACT

SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection. One Sentence SummaryLY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.

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