Federal University of São Paulo

About: Federal University of São Paulo is a education organization based out in São Paulo, Brazil. It is known for research contribution in the topics: Population & Medicine. The organization has 27971 authors who have published 49365 publications receiving 935536 citations. The organization is also known as: Universidade Federal de São Paulo & Universidade Federal de Sao Paulo.

Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis

Abstract: A growing body of literature on the 2019 novel coronavirus (SARS-CoV-2) is becoming available, but a synthesis of available data has not been conducted. We performed a scoping review of currently available clinical, epidemiological, laboratory, and chest imaging data related to the SARS-CoV-2 infection. We searched MEDLINE, Cochrane CENTRAL, EMBASE, Scopus and LILACS from 01 January 2019 to 24 February 2020. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. Qualitative synthesis and meta-analysis were conducted using the clinical and laboratory data, and random-effects models were applied to estimate pooled results. A total of 61 studies were included (59,254 patients). The most common disease-related symptoms were fever (82%, 95% confidence interval (CI) 56%–99%; n = 4410), cough (61%, 95% CI 39%–81%; n = 3985), muscle aches and/or fatigue (36%, 95% CI 18%–55%; n = 3778), dyspnea (26%, 95% CI 12%–41%; n = 3700), headache in 12% (95% CI 4%–23%, n = 3598 patients), sore throat in 10% (95% CI 5%–17%, n = 1387) and gastrointestinal symptoms in 9% (95% CI 3%–17%, n = 1744). Laboratory findings were described in a lower number of patients and revealed lymphopenia (0.93 × 109/L, 95% CI 0.83–1.03 × 109/L, n = 464) and abnormal C-reactive protein (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL; n = 1637). Radiological findings varied, but mostly described ground-glass opacities and consolidation. Data on treatment options were limited. All-cause mortality was 0.3% (95% CI 0.0%–1.0%; n = 53,631). Epidemiological studies showed that mortality was higher in males and elderly patients. The majority of reported clinical symptoms and laboratory findings related to SARS-CoV-2 infection are non-specific. Clinical suspicion, accompanied by a relevant epidemiological history, should be followed by early imaging and virological assay.

Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection

Abstract: Prions are composed of an isoform of a normal sialoglycoprotein called PrP(c), whose physiological role has been under investigation, with focus on the screening for ligands. Our group described a membrane 66 kDa PrP(c)-binding protein with the aid of antibodies against a peptide deduced by complementary hydropathy. Using these antibodies in western blots from two-dimensional protein gels followed by sequencing the specific spot, we have now identified the molecule as stress-inducible protein 1 (STI1). We show that this protein is also found at the cell membrane besides the cytoplasm. Both proteins interact in a specific and high affinity manner with a K(d) of 10(-7) M. The interaction sites were mapped to amino acids 113-128 from PrP(c) and 230-245 from STI1. Cell surface binding and pull-down experiments showed that recombinant PrP(c) binds to cellular STI1, and co-immunoprecipitation assays strongly suggest that both proteins are associated in vivo. Moreover, PrP(c) interaction with either STI1 or with the peptide we found that represents the binding domain in STI1 induce neuroprotective signals that rescue cells from apoptosis.

Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine (preprint)

Abstract: Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, MHRA, with a regimen of two standard doses given with an interval of between 4 and 12 weeks The planned rollout in the UK will involve vaccinating people in high risk categories with their first dose immediately, and delivering the second dose 12 weeks laterHere we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered Methods: We present data from phase III efficacy trials of ChAdOx1 nCoV-19 in the United Kingdom and Brazil, and phase I/II clinical trials in the UK and South Africa, against symptomatic disease caused by SARS-CoV-2 The data cut-off date for these analyses was 7th December 2020 The accumulated cases of COVID-19 disease at this cut-off date exceeds the number required for a pre-specified final analysis, which is also presented As previously described, individuals over 18 years of age were randomised 1:1 to receive two standard doses (SD) of ChAdOx1 nCoV-19 (5x1010 viral particles) or a control vaccine/saline placebo In the UK trial efficacy cohort a subset of participants received a lower dose (LD, 22x1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose All cases with a nucleic acid amplification test (NAAT) were adjudicated for inclusion in the analysis, by a blinded independent endpoint review committee Studies are registered at ISRCTN89951424 and ClinicalTrialsgov; NCT04324606, NCT04400838, and NCT04444674 Findings: 17,177 baseline seronegative trial participants were eligible for inclusion in the efficacy analysis, 8948 in the UK, 6753 in Brazil and 1476 in South Africa, with 619 documented NAAT +ve infections of which 332 met the primary endpoint of symptomatic infection >14 days post dose 2The primary analysis of overall vaccine efficacy >14 days after the second dose including LD/SD and SD/SD groups, based on the prespecified criteria was 667% (574%, 740%) There were no hospitalisations in the ChAdOx1 nCoV-19 group after the initial 21 day exclusion period, and 15 in the control groupVaccine efficacy after a single standard dose of vaccine from day 22 to day 90 post vaccination was 76% (59%, 86%), and modelled analysis indicated that protection did not wane during this initial 3 month period Similarly, antibody levels were maintained during this period with minimal waning by day 90 day (GMR 066, 95% CI 059, 074)In the SD/SD group, after the second dose, efficacy was higher with a longer prime-boost interval: VE 824% 95%CI 627%, 917% at 12+ weeks, compared with VE 549%, 95%CI 327%, 697% at <6 weeks These observations are supported by immunogenicity data which showed binding antibody responses more than 2-fold higher after an interval of 12 or more weeks compared with and interval of less than 6 weeks GMR 219 (212, 226) in those who were 18-55 years of age Interpretation: ChAdOx1 nCoV-19 vaccination programmes aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3 month period is an effective strategy for reducing disease, and may be the optimal for rollout of a pandemic vaccine when supplies are limited in the short term Trial Registration: Studies are registered at ISRCTN89951424 and ClinicalTrialsgov; NCT04324606, NCT04400838, and NCT04444674 Funding: UKRI, NIHR, CEPI, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D’OR, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and Astra Zeneca Conflict of Interest: Oxford University has entered into a partnership with Astra Zeneca for further development of ChAdOx1 nCoV-19 SCG is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine TL is named as aninventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project PMF is a consultant to Vaccitech AJP is Chair of UK DeptHealth and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), but does not participate in discussions on COVID-19 vaccines, and is a member of the WHO’sSAGE AJP and SNF are NIHR Senior Investigator The views expressed in this article do not necessarily represent the views of DHSC, JCVI, NIHR or WHO AVSH reports personal feesfrom Vaccitech, outside the submitted work and has a patent on ChAdOx1 licensed to Vaccitech, and may benefit from royalty income to the University of Oxford from sales of this vaccine by AstraZeneca and sublicensees MS reports grants from NIHR, non-financial support fromAstraZeneca, during the conduct of the study; grants from Janssen, grants fromGlaxoSmithKline, grants from Medimmune, grants from Novavax, grants and non-financialsupport from Pfizer, grants from MCM, outside the submitted work CG reports personal fees from the Duke Human Vaccine Institute, outside of the submitted work SNF reports grants from Janssen and Valneva, outside the submitted work ADD reports grants and personal fees from AstraZeneca, outside of the submitted work In addition, ADD has a patent manufacturingprocess for ChAdOx vectors with royalties paid to AstraZeneca, and a patent ChAdOx2 vector with royalties paid to AstraZeneca The other authors declare no competing interests

Planning cancer control in Latin America and the Caribbean

Abstract: Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.