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Showing papers by "Universidade Federal de Minas Gerais published in 2021"


Journal ArticleDOI
15 Apr 2021-Nature
TL;DR: A newly arisen lineage of SARS-CoV-2 (designated 501Y.V2) was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province.
Abstract: Continued uncontrolled transmission of SARS-CoV-2 in many parts of the world is creating conditions for substantial evolutionary changes to the virus1,2. Here we describe a newly arisen lineage of SARS-CoV-2 (designated 501Y.V2; also known as B.1.351 or 20H) that is defined by eight mutations in the spike protein, including three substitutions (K417N, E484K and N501Y) at residues in its receptor-binding domain that may have functional importance3-5. This lineage was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province. This lineage spread rapidly, and became dominant in Eastern Cape, Western Cape and KwaZulu-Natal provinces within weeks. Although the full import of the mutations is yet to be determined, the genomic data-which show rapid expansion and displacement of other lineages in several regions-suggest that this lineage is associated with a selection advantage that most plausibly results from increased transmissibility or immune escape6-8.

1,171 citations


Journal ArticleDOI
Nuno R. Faria, Thomas A. Mellan1, Charles Whittaker1, Ingra Morales Claro2, Darlan da Silva Candido2, Darlan da Silva Candido3, Swapnil Mishra1, Myuki A E Crispim, Flavia C. S. Sales2, Iwona Hawryluk1, John T. McCrone4, Ruben J.G. Hulswit3, Lucas A M Franco2, Mariana S. Ramundo2, Jaqueline Goes de Jesus2, Pamela S Andrade2, Thais M. Coletti2, Giulia M. Ferreira5, Camila A. M. Silva2, Erika R. Manuli2, Rafael Henrique Moraes Pereira, Pedro S. Peixoto2, Moritz U. G. Kraemer3, Nelson Gaburo, Cecilia da C. Camilo, Henrique Hoeltgebaum1, William Marciel de Souza2, Esmenia C. Rocha2, Leandro Marques de Souza2, Mariana C. Pinho2, Leonardo José Tadeu de Araújo6, Frederico S V Malta, Aline B. de Lima, Joice do P. Silva, Danielle A G Zauli, Alessandro C. S. Ferreira, Ricardo P Schnekenberg3, Daniel J Laydon1, Patrick G T Walker1, Hannah M. Schlüter1, Ana L. P. dos Santos, Maria S. Vidal, Valentina S. Del Caro, Rosinaldo M. F. Filho, Helem M. dos Santos, Renato Santana Aguiar7, José Luiz Proença-Módena8, Bruce Walker Nelson9, James A. Hay10, Melodie Monod1, Xenia Miscouridou1, Helen Coupland1, Raphael Sonabend1, Michaela A. C. Vollmer1, Axel Gandy1, Carlos A. Prete2, Vitor H. Nascimento2, Marc A. Suchard11, Thomas A. Bowden3, Sergei L Kosakovsky Pond12, Chieh-Hsi Wu13, Oliver Ratmann1, Neil M. Ferguson1, Christopher Dye3, Nicholas J. Loman14, Philippe Lemey15, Andrew Rambaut4, Nelson Abrahim Fraiji, Maria Perpétuo Socorro Sampaio Carvalho, Oliver G. Pybus3, Oliver G. Pybus16, Seth Flaxman1, Samir Bhatt17, Samir Bhatt1, Ester Cerdeira Sabino2 
21 May 2021-Science
TL;DR: In this article, the authors used a two-category dynamical model that integrates genomic and mortality data to estimate that P.1 may be 1.7-to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.
Abstract: Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

985 citations


Journal ArticleDOI
TL;DR: The growth of WikiPathways over the last three years is shown, the new communities and collaborations of pathway authors and curators are highlighted, and various technologies to connect to external resources and initiatives are described.
Abstract: WikiPathways (https://www.wikipathways.org) is a biological pathway database known for its collaborative nature and open science approaches. With the core idea of the scientific community developing and curating biological knowledge in pathway models, WikiPathways lowers all barriers for accessing and using its content. Increasingly more content creators, initiatives, projects and tools have started using WikiPathways. Central in this growth and increased use of WikiPathways are the various communities that focus on particular subsets of molecular pathways such as for rare diseases and lipid metabolism. Knowledge from published pathway figures helps prioritize pathway development, using optical character and named entity recognition. We show the growth of WikiPathways over the last three years, highlight the new communities and collaborations of pathway authors and curators, and describe various technologies to connect to external resources and initiatives. The road toward a sustainable, community-driven pathway database goes through integration with other resources such as Wikidata and allowing more use, curation and redistribution of WikiPathways content.

378 citations


Journal ArticleDOI
TL;DR: The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90)1..
Abstract: The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90)1. Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections2. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref. 3), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref. 4), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020 (ref. 5).

302 citations


Journal ArticleDOI
TL;DR: Information about the impact of epidemics on parents and children is relevant to policy makers to aid them in developing strategies to help families cope with epidemic/pandemic-driven adversity and ensure their children’s healthy development.
Abstract: Objective This was a systematic review of studies that examined the impact of epidemics or social restriction on mental and developmental health in parents and children/adolescents. Source of data The PubMed, WHO COVID-19, and SciELO databases were searched on March 15, 2020, and on April 25, 2020, filtering for children (0–18 years) and humans. Synthesis of data The tools used to mitigate the threat of a pandemic such as COVID-19 may very well threaten child growth and development. These tools — such as social restrictions, shutdowns, and school closures — contribute to stress in parents and children and can become risk factors that threaten child growth and development and may compromise the Sustainable Development Goals. The studies reviewed suggest that epidemics can lead to high levels of stress in parents and children, which begin with concerns about children becoming infected. These studies describe several potential mental and emotional consequences of epidemics such as COVID-19, H1N1, AIDS, and Ebola: severe anxiety or depression among parents and acute stress disorder, post-traumatic stress, anxiety disorders, and depression among children. These data can be related to adverse childhood experiences and elevated risk of toxic stress. The more adverse experiences, the greater the risk of developmental delays and health problems in adulthood, such as cognitive impairment, substance abuse, depression, and non-communicable diseases. Conclusion Information about the impact of epidemics on parents and children is relevant to policy makers to aid them in developing strategies to help families cope with epidemic/pandemic-driven adversity and ensure their children’s healthy development.

189 citations


Journal ArticleDOI
18 Apr 2021-Viruses
TL;DR: In this paper, a comprehensive review of adverse post-COVID health outcomes and potential long-coVID effects was conducted, and the authors observed that such adverse outcomes were not localized.
Abstract: The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain-Barre syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.

170 citations


Journal ArticleDOI
TL;DR: In a survey conducted by the Autoimmune Encephalitis Alliance Clinicians Network as mentioned in this paper, the authors evaluated available evidence for each step in autoimmune encephalitis management and provided expert opinion when evidence is lacking.
Abstract: The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

157 citations


Posted ContentDOI
Nuno R. Faria1, Nuno R. Faria2, Nuno R. Faria3, Thomas A. Mellan1, Charles Whittaker1, Ingra Morales Claro3, Darlan da Silva Candido2, Darlan da Silva Candido3, Swapnil Mishra1, Myuki A E Crispim, Flavia C. S. Sales3, Iwona Hawryluk1, John T. McCrone4, Ruben J.G. Hulswit2, Lucas A M Franco3, Mariana S. Ramundo3, Jaqueline Goes de Jesus3, Pamela S Andrade3, Thais M. Coletti3, Giulia M. Ferreira5, Camila A. M. Silva3, Erika R. Manuli3, Rafael Henrique Moraes Pereira, Pedro S. Peixoto3, Moritz U. G. Kraemer2, Nelson Gaburo, Cecilia da C. Camilo, Henrique Hoeltgebaum1, William Marciel de Souza3, Esmenia C. Rocha3, Leandro Marques de Souza3, Mariana C. Pinho3, Leonardo José Tadeu de Araújo6, Frederico S V Malta, Aline B. de Lima, Joice do P. Silva, Danielle A G Zauli, Alessandro C. S. Ferreira, Ricardo P Schnekenberg2, Daniel J Laydon1, Patrick G T Walker1, Hannah M. Schlüter1, Ana L. P. dos Santos, Maria S. Vidal, Valentina S. Del Caro, Rosinaldo M. F. Filho, Helem M. dos Santos, Renato Santana Aguiar7, José Luiz Proença Modena8, Bruce Walker Nelson9, James A. Hay10, Melodie Monod1, Xenia Miscouridou1, Helen Coupland1, Raphael Sonabend1, Michaela A. C. Vollmer1, Axel Gandy1, Marc A. Suchard11, Thomas A. Bowden2, Sergei L Kosakovsky Pond12, Chieh-Hsi Wu13, Oliver Ratmann1, Neil M. Ferguson1, Christopher Dye2, Nicholas J. Loman14, Philippe Lemey15, Andrew Rambaut4, Nelson Abrahim Fraiji, Maria Perpétuo Socorro Sampaio Carvalho, Oliver G. Pybus2, Oliver G. Pybus16, Seth Flaxman1, Samir Bhatt1, Samir Bhatt17, Ester Cerdeira Sabino3 
03 Mar 2021-medRxiv
TL;DR: In this paper, the emergence and circulation of a new SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor.
Abstract: Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4–2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness. One-Sentence Summary We report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.

155 citations


Journal ArticleDOI
TL;DR: A phase 3 clinical trial conducted in healthcare professionals in Brazil demonstrated that the inactivated CoronaVac vaccine has a good safety profile and is efficacious against any symptomatic SARS-CoV-2 infections and highly protective against moderate and severe COVID-19.
Abstract: Background: Vaccines are urgently needed to tackle the unprecedented morbidity and mortality of COVID-19. Administration of inactivated viruses are the common and mature platform of developing new vaccines. CoronaVac is an inactivated vaccine that has undergone preclinical tests and phase I/II clinical trials. Methods: We conducted a randomised, double-blind, placebo-controlled phase 3 clinical trial with CoronaVac among healthy healthcare professionals in 16 centres in Brazil. Participants received two doses of vaccine (3 μg in 0.5 mL) vaccine or placebo at day 0 and 14. The primary efficacy endpoint was the number of symptomatic COVID-19 cases confirmed by RT-PCR 14 days after the second dose of the vaccine. Prevention of disease severity was a major secondary efficacy endpoint, and adverse events incidence up to seven days after immunization was the primary safety outcome. The trial was registered at ClinicalTrials.gov, NCT04456595. Findings: Between July 21 and Dec 16, 2020, 12 396 participants were enrolled and received at least one vaccine or placebo dose. There were 9,823 participants who received the two doses and were followed for at least 14 days and had, therefore, reached the final efficacy analysis. There were 253 confirmed COVID-19 cases in the cohort: 85 cases (11.0/100 person-year) among 4,953 participants in the vaccine group, and 168 cases (22·3/100 person-year) among 4,870 participants in the placebo group. The primary efficacy against symptomatic COVID-19 was 50·7% (95%CI 36·0-62·0). The secondary efficacy against cases requiring assistance (score ≥3) and moderate and severe cases (score ≥4) were 83·7% (95%CI 58·0-93.7) and 100% (95%CI 56·4-100.0) respectively. All 6 cases of severe COVID-19 occurred in the placebo group. The incidence of adverse reactions, which was mainly pain at the administration site, was higher in the vaccine group (77·1%) than in the placebo group (66·4%). There were 67 serious adverse events reported by 64 participants and all were determined to be unrelated to vaccination, including two fatal cases. In a subset of participants, neutralizing antibody assays showed similar seroconversion and geometric mean titres against B.1.128, P.1, and P.2 variants. Interpretation: A phase 3 clinical trial conducted in healthcare professionals in Brazil demonstrated that the inactivated CoronaVac vaccine has a good safety profile and is efficacious against any symptomatic SARS-CoV-2 infections and highly protective against moderate and severe COVID-19.

152 citations


Journal ArticleDOI
TL;DR: In this article, the effect of COVID-19 during pregnancy on mothers and neonates was quantified with the risk factors known to be associated with preeclampsia analyzed in each group.

137 citations


Journal ArticleDOI
TL;DR: This chapter describes some of the sensory stimuli that macrophages perceive and the responses they make to these stimuli to achieve their prime directive, which is the maintenance of homeostasis.
Abstract: There have been many chapters written about macrophage polarization. These chapters generally focus on the role of macrophages in orchestrating immune responses by highlighting the T-cell-derived cytokines that shape these polarizing responses. This bias toward immunity is understandable, given the importance of macrophages to host defense. However, macrophages are ubiquitous and are involved in many different cellular processes, and describing them as immune cells is undoubtedly an oversimplification. It disregards their important roles in development, tissue remodeling, wound healing, angiogenesis, and metabolism, to name just a few processes. In this chapter, we propose that macrophages function as transducers in the body. According to Wikipedia, "A transducer is a device that converts energy from one form to another." The word transducer is a term used to describe both the "sensor," which can interpret a wide range of energy forms, and the "actuator," which can switch voltages or currents to affect the environment. Macrophages are able to sense a seemingly endless variety of inputs from their environment and transduce these inputs into a variety of different response outcomes. Thus, rather than functioning as immune cells, they should be considered more broadly as cellular transducers that interpret microenvironmental changes and actuate vital tissue responses. In this chapter, we will describe some of the sensory stimuli that macrophages perceive and the responses they make to these stimuli to achieve their prime directive, which is the maintenance of homeostasis.

Posted ContentDOI
Eduan Wilkinson1, Eduan Wilkinson2, Marta Giovanetti3, Marta Giovanetti4  +323 moreInstitutions (58)
09 Sep 2021-Science
TL;DR: In this paper, the authors describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories and show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished following the early introduction of international travel restrictions.
Abstract: The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants.

Journal ArticleDOI
TL;DR: In this paper, the authors proposed a Product Emission Intensity Index (PEII) associated with the production of 786 goods, which is a weighted average of the emissions of the countries that export each given product with revealed comparative advantage.

Journal ArticleDOI
18 Feb 2021-Nature
TL;DR: In this paper, hyperspectral optical images of twisted bilayer graphene were obtained by using a nano-Raman spectroscope, which revealed the localization of lattice dynamics, with the presence of solitons and topological points causing detectable spectral variations.
Abstract: Twisted bilayer graphene is created by slightly rotating the two crystal networks in bilayer graphene with respect to each other. For small twist angles, the material undergoes a self-organized lattice reconstruction, leading to the formation of a periodically repeated domain1-3. The resulting superlattice modulates the vibrational3,4 and electronic5,6 structures within the material, leading to changes in the behaviour of electron-phonon coupling7,8 and to the observation of strong correlations and superconductivity9. However, accessing these modulations and understanding the related effects are challenging, because the modulations are too small for experimental techniques to accurately resolve the relevant energy levels and too large for theoretical models to properly describe the localized effects. Here we report hyperspectral optical images, generated by a nano-Raman spectroscope10, of the crystal superlattice in reconstructed (low-angle) twisted bilayer graphene. Observations of the crystallographic structure with visible light are made possible by the nano-Raman technique, which reveals the localization of lattice dynamics, with the presence of strain solitons and topological points1 causing detectable spectral variations. The results are rationalized by an atomistic model that enables evaluation of the local density of the electronic and vibrational states of the superlattice. This evaluation highlights the relevance of solitons and topological points for the vibrational and electronic properties of the structures, particularly for small twist angles. Our results are an important step towards understanding phonon-related effects at atomic and nanometric scales, such as Jahn-Teller effects11 and electronic Cooper pairing12-14, and may help to improve device characterization15 in the context of the rapidly developing field of twistronics16.

Journal ArticleDOI
TL;DR: In this paper, the clinical features of children and adolescents hospitalised with laboratory-confirmed SARS-CoV-2 infection and evaluated the risk factors for COVID-19-related death in this population.

Journal ArticleDOI
TL;DR: This critical review presents a contribution to the emerging knowledge concerning the theoretical and experimental studies on the toxicity of MIONs and provides comprehensive coverage of the recent progress on designing and developing iron oxide-based nanomaterials through a green synthesis strategy, including the use of benign solvents and ligands.

Journal ArticleDOI
TL;DR: In this paper, the accepted manuscript of an article published by Elsevier in Additive Manufacturing on 2/10/2021, available online: https://doi.org/10.1016/j.addma.2021.102378
Abstract: This is an accepted manuscript of an article published by Elsevier in Additive Manufacturing on 02/10/2021, available online: https://doi.org/10.1016/j.addma.2021.102378 The accepted version of the publication may differ from the final published version.

Journal ArticleDOI
01 Apr 2021
TL;DR: In this paper, a randomized clinical trial was conducted in Brazil to determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting.
Abstract: Importance Data on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed. Objective To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. Design, Setting, and Participants This randomized clinical trial was conducted in Brazil. Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020. Interventions Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. Main Outcomes and Measures The primary outcomes were COVID-19–associated hospitalization and death assessed at 90 days after randomization. COVID-19–associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary outcomes: all-cause hospitalization, viral clearance, symptom resolution, and adverse events. Results Of 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavir-ritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19–associated hospitalization (hydroxychloroquine: hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir: HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine: odds ratio [OR], 0.91 [95% CI, 0.82-1.02]; lopinavir-ritonavir: OR, 1.04 [95% CI, 0.94-1.16]). At the end of the trial, there were 3 fatalities recorded, 1 in the placebo group and 2 in the lopinavir-ritonavir intervention group. Conclusions and Relevance In this randomized clinical trial, neither hydroxychloroquine nor lopinavir-ritonavir showed any significant benefit for decreasing COVID-19–associated hospitalization or other secondary clinical outcomes. This trial suggests that expedient clinical trials can be implemented in low-income settings even during the COVID-19 pandemic. Trial Registration ClinicalTrials.gov Identifier:NCT04403100

Journal ArticleDOI
TL;DR: In this paper, a multicenter, randomized, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of Covid-19 symptoms (dry cough, fever, and fatigue) were enrolled.
Abstract: Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on SARS-CoV-2 infection. In a multicenter, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of Covid-19 symptoms (dry cough, fever, and/or fatigue) were enrolled. After confirmation of SARS-CoV2 infection by RT-PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, TID, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation, and hospitalisation rate. Adverse events were also assessed. From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median time from symptom onset to first dose of study drug was 5 (4–5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was also reduced after nitazoxanide compared to placebo (p=0.006). The percent viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. In patients with mild Covid-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

Journal ArticleDOI
01 Jun 2021-PLOS ONE
TL;DR: In this article, the authors describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases, including interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer.
Abstract: Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.


Journal ArticleDOI
TL;DR: In this article, the authors used various analytical tools for identification and characterization of microplastics and their transformation products in environmental compartments, including membrane filtration and coagulation-flocculation-settling treatments.

Journal ArticleDOI
TL;DR: In this article, a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.

Journal ArticleDOI
Maria Lc Iurilli1, Bin Zhou1, James E. Bennett1, Rodrigo M. Carrillo-Larco1  +1399 moreInstitutions (374)
09 Mar 2021-eLife
TL;DR: In this article, the authors investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants.
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.


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TL;DR: In this paper, the authors investigated the relationship between historical deforestation and rainfall at different geographical scales across the Southern Brazilian Amazon (SBA), and assessed impacts of deforestation policy scenarios on the region's agriculture.
Abstract: It has been suggested that rainfall in the Amazon decreases if forest loss exceeds some threshold, but the specific value of this threshold remains uncertain. Here, we investigate the relationship between historical deforestation and rainfall at different geographical scales across the Southern Brazilian Amazon (SBA). We also assess impacts of deforestation policy scenarios on the region’s agriculture. Forest loss of up to 55–60% within 28 km grid cells enhances rainfall, but further deforestation reduces rainfall precipitously. This threshold is lower at larger scales (45–50% at 56 km and 25–30% at 112 km grid cells), while rainfall decreases linearly within 224 km grid cells. Widespread deforestation results in a hydrological and economic negative-sum game, because lower rainfall and agricultural productivity at larger scales outdo local gains. Under a weak governance scenario, SBA may lose 56% of its forests by 2050. Reducing deforestation prevents agricultural losses in SBA up to US$ 1 billion annually. Deforestation in the Amazon region has suggested to influence precipitation in a non-linear way. Here, the authors show that forest loss is associated with decreasing precipitation after a scale-dependent threshold is crossed, which can cause stress on agriculture if deforestation is expanded.

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TL;DR: Investigating dysfunctional information sharing on WhatsApp and Facebook suggests that the intimate nature of WhatsApp communication has important consequences for the dynamics of misinformation sharing, particularly with regard to facilitating social corrections.
Abstract: In this study, we investigate dysfunctional information sharing on WhatsApp and Facebook, focusing on two explanatory variables—frequency of political talk and cross-cutting exposure—and potential ...

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TL;DR: The increased expression of these severe acute respiratory syndrome coronavirus 2 cell entry–associated genes in the placenta in the first trimester of pregnancy compared with those in later stages of pregnancy suggests the possibility of differential susceptibility to placental entry to severe acute virus 2 across pregnancy.

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31 Jan 2021-Water
TL;DR: In this article, the authors identify major gaps in the biological assessment and rehabilitation of rivers worldwide by focusing on the best examples in Asia, Europe, Oceania, and North, Central, and South America.
Abstract: The biological assessment of rivers i.e., their assessment through use of aquatic assemblages, integrates the effects of multiple-stressors on these systems over time and is essential to evaluate ecosystem condition and establish recovery measures. It has been undertaken in many countries since the 1990s, but not globally. And where national or multi-national monitoring networks have gathered large amounts of data, the poor water body classifications have not necessarily resulted in the rehabilitation of rivers. Thus, here we aimed to identify major gaps in the biological assessment and rehabilitation of rivers worldwide by focusing on the best examples in Asia, Europe, Oceania, and North, Central, and South America. Our study showed that it is not possible so far to draw a world map of the ecological quality of rivers. Biological assessment of rivers and streams is only implemented officially nation-wide and regularly in the European Union, Japan, Republic of Korea, South Africa, and the USA. In Australia, Canada, China, New Zealand, and Singapore it has been implemented officially at the state/province level (in some cases using common protocols) or in major catchments or even only once at the national level to define reference conditions (Australia). In other cases, biological monitoring is driven by a specific problem, impact assessments, water licenses, or the need to rehabilitate a river or a river section (as in Brazil, South Korea, China, Canada, Japan, Australia). In some countries monitoring programs have only been explored by research teams mostly at the catchment or local level (e.g., Brazil, Mexico, Chile, China, India, Malaysia, Thailand, Vietnam) or implemented by citizen science groups (e.g., Southern Africa, Gambia, East Africa, Australia, Brazil, Canada). The existing large-extent assessments show a striking loss of biodiversity in the last 2-3 decades in Japanese and New Zealand rivers (e.g., 42% and 70% of fish species threatened or endangered, respectively). A poor condition (below Good condition) exists in 25% of South Korean rivers, half of the European water bodies, and 44% of USA rivers, while in Australia 30% of the reaches sampled were significantly impaired in 2006. Regarding river rehabilitation, the greatest implementation has occurred in North America, Australia, Northern Europe, Japan, Singapore, and the Republic of Korea. Most rehabilitation measures have been related to improving water quality and river connectivity for fish or the improvement of riparian vegetation. The limited extent of most rehabilitation measures (i.e., not considering the entire catchment) often constrains the improvement of biological condition. Yet, many rehabilitation projects also lack pre-and/or post-monitoring of ecological condition, which prevents assessing the success and shortcomings of the recovery measures. Economic constraints are the most cited limitation for implementing monitoring programs and rehabilitation actions, followed by technical limitations, limited knowledge of the fauna and flora and their life-history traits (especially in Africa, South America and Mexico), and poor awareness by decision-makers. On the other hand, citizen involvement is recognized as key to the success and sustainability of rehabilitation projects. Thus, establishing rehabilitation needs, defining clear goals, tracking progress towards achieving them, and involving local populations and stakeholders are key recommendations for rehabilitation projects (Table 1). Large-extent and long-term monitoring programs are also essential to provide a realistic overview of the condition of rivers worldwide. Soon, the use of DNA biological samples and eDNA to investigate aquatic diversity could contribute to reducing costs and thus increase monitoring efforts and a more complete assessment of biodiversity. Finally, we propose developing transcontinental teams to elaborate and improve technical guidelines for implementing biological monitoring programs and river rehabilitation and establishing common financial and technical frameworks for managing international catchments. We also recommend providing such expert teams through the United Nations Environment Program to aid the extension of biomonitoring, bioassessment, and river rehabilitation knowledge globally.

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TL;DR: In this article, the authors analyzed the impact of coinfections on the outcome of hospitalized COVID-19 patients and found that coinfected patients stayed hospitalized longer and had an increased odds of dying (odds ratio (OR): 13.45; R2 ǫ = 0.31).