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1.
Washington, D.C.; PAHO; 2022-01-11. (PAHO/IMS/EIH/COVID-19/22-0001).
Não convencional em Inglês | PAHO-IRIS | ID: phr-52719

RESUMO

This document includes the results of a rapid systematic review of current available literature. The information included in this review reflects the evidence as of the date posted in the document. In recognition of the fact that there are numerous ongoing clinical studies, PAHO will periodically update this review and corresponding recommendations as new evidence becomes available.


Assuntos
COVID-19 , Coronavirus , Infecções por Coronavirus , Betacoronavirus , Pandemias , Medicina de Emergência Baseada em Evidências
2.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-474769

RESUMO

Monocolonal antibodies (mAbs) are currently used for active immunization of COVID-19 in immunocompromised patients. We herein show that in spite there are variations in susceptibility to available mAbs that are authorized for clinical use in France tested on the original B.1.1 virus and 9 variants of concern or of interest, the cocktail casirivimab/imdevimab (REGN-CoV-2) showed a major synergistic effect. However, none of the four mAbs either alone or in combination neutralized the new Omicron variant. Our data strongly warrant a reinforcement of protective measures against infection for immunocompromised patients.

3.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-474639

RESUMO

The emergence and rapid spread of the Omicron variant of SARS-CoV-2, which has more than 30 substitutions in the spike glycoprotein, compromises the efficacy of currently available vaccines and therapeutic antibodies. Using a clinical strain of the Omicron variant, we analyzed the neutralizing power of eight currently used monoclonal antibodies compared to the ancestral B.1 BavPat1 D614G strain. We observed that six of these antibodies have lost their ability to neutralize the Omicron variant. Of the antibodies still having neutralizing activity, Sotrovimab/Vir-7831 shows the smallest reduction in activity, with a factor change of 3.1. Cilgavimab/AZD1061 alone shows a reduction in efficacy of 15.8, resulting in a significant loss of activity for the Evusheld cocktail (42.6 fold reduction) in which the other antibody, Tixagevimab, does not retain significant activity against Omicron. Our results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.

4.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-475918

RESUMO

Though it has been 2 years since the start of the Coronavirus Disease 19 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, very little progress has been made to identify curative therapies to treat COVID-19 and other inflammatory diseases which remain a major unmet need in medicine. Our study sought to identify drivers of disease severity and death to develop tailored immunotherapy strategies to halt disease progression. Here we assembled the Mount Sinai COVID-19 Biobank which was comprised of ~600 hospitalized patients followed longitudinally during the peak of the pandemic. Moderate disease and survival were associated with a stronger antigen (Ag) presentation and effector T cell signature, while severe disease and death were associated with an altered Ag presentation signature, increased numbers of circulating inflammatory, immature myeloid cells, and extrafollicular activated B cells associated with autoantibody formation. Strikingly, we found that in severe COVID-19 patients, lung tissue resident alveolar macrophages (AM) were not only severely depleted, but also had an altered Ag presentation signature, and were replaced by inflammatory monocytes and monocyte-derived macrophages (MoM{phi}). Notably, the size of the AM pool correlated with recovery or death, while AM loss and functionality were restored in patients that recovered. These data therefore suggest that local and systemic myeloid cell dysregulation is a driver of COVID-19 severity and that modulation of AM numbers and functionality in the lung may be a viable therapeutic strategy for the treatment of critical lung inflammatory illnesses.

5.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-475015

RESUMO

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes various neurological symptoms in coronavirus disease 2019 (COVID-19) patients. The most dominant immune cells in the brain are microglia. Yet, the relationship between neurological manifestations, neuroinflammation, and host immune response of microglia to SARS-CoV-2 has not been well characterized. Here, we report that SARS-CoV-2 can directly infect human microglia, eliciting M1-like pro-inflammatory responses, followed by cytopathic effects. Specifically, SARS-CoV-2 infected human microglial clone 3 (HMC3), leading to inflammatory activation and cell death. RNA-seq analysis also revealed that ER stress and immune responses were induced in the early and apoptotic processes in the late phase of viral infection. SARS-CoV-2-infected HMC3 showed the M1 phenotype and produced pro-inflammatory cytokines such as interleukin (IL)-1{beta}, IL-6, and tumour necrosis factor (TNF-), but not the anti-inflammatory cytokine IL-10. After this pro-inflammatory activation, SARS-CoV-2 infection promoted both intrinsic and extrinsic death receptor-mediated apoptosis in HMC3. Using K18-hACE2 transgenic mice, murine microglia were also infected by intranasal inoculation of SARS-CoV-2. This infection induced the acute production of pro-inflammatory microglial IL-6 and TNF- and provoked a chronic loss of microglia. Our findings suggest that microglia are potential mediators of SARS-CoV-2-induced neurological problems and, consequently, can be targets of therapeutic strategies against neurological diseases in COVID-19 patients. IMPORTANCERecent studies reported neurological manifestations and complications in COVID-19 patients, which are associated with neuroinflammation. As microglia are the dominant immune cells in brains, it needs to be elucidate the relationship between neuroinflammation and host immune response of microglia to SARS-CoV-2. Here, we suggest that SARS-CoV-2 can directly infect human microglia with cytopathic effect (CPE) using human microglial clone 3 (HMC3). The infected microglia were promoted to pro-inflammatory activation following apoptotic cell death. This pro-inflammatory activation was accompanied by the high production of pro-inflammatory cytokines, and led to neurotoxic-M1 phenotype polarization. In vivo, murine microglia were infected and produced pro-inflammatory cytokines and provoked a chronic loss using K18-hACE2 mice. Thus, our data present that SARS-CoV-2-infected microglia are potential mediators of neurological problems in COVID-19 patients. In addition, HMC3 cells are susceptible to SARS-CoV-2 and exhibit the CPE, which can be further used to investigate cellular and molecular mechanisms of neuroinflammation reported in COVID-19 patients.

6.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21267090

RESUMO

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and calibration of an stochastic agent-based model Covasim to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. We used these estimates in Covasim (calibrated between September 01, 2020 and June 20, 2021), in June 2021, to explore whether planned relaxation of restrictions should proceed or be delayed. We found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination.

7.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268641

RESUMO

As COVID-19 continues to pose major risk for vulnerable populations including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate blockade of SARS-CoV-2 pseudovirus infection of target cells. Omicron pseudovirus infected normal human small airway epithelial (HSAE) cells significantly less than D614G or Delta variant pseudovirus, and GLPG-0187 effectively blocked SARS-CoV-2 pseudovirus infection in a dose-dependent manner across multiple viral variants. GLPG-0187 inhibited Omicron and Delta pseudovirus infection of HSAE cells more significantly than other variants. Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced inhibition of pseudovirus infection by GLPG-0187. Because integrins activate TGF-{beta} signaling, we compared plasma levels of active and total TGF-{beta} in COVID-19+ patients. Plasma TGF-{beta}1 levels correlated with age, race, and number of medications upon presentation with COVID-19, but not with sex. Total plasma TGF-{beta}1 levels correlated with activated TGF-{beta}1 levels. In our preclinical studies, Omicron infects lower airway lung cells less efficiently than other COVID-19 variants. Moreover, inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and may mitigate COVID-19 severity through decreased TGF-{beta}1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations.

8.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268603

RESUMO

Patients in need of urgent inpatient treatment were recruited prospectively. A rapid point of care PCR test (POC-PCR; Liat(R)) for SARS-CoV2 was conducted in the ED and a second PCR-test from the same swab was ordered in the central laboratory (CL-PCR). POC-PCR analyzers were digitally integrated in the laboratory information system. Overall, 160 ED patients were included. A valid POC-PCR-test result was available in 96.3% (n=154) of patients. N=16 patients tested positive for SARS-CoV-2 (10.0%). The POC PCR test results were available within 102 minutes (median, IQR: 56-211), which was significantly earlier compared to the CL PCR (811 minutes; IQR: 533-1289, p < 0.001). The diagnostic accuracy of the POC-PCR test was 100%. The implementation and digital LIS integration was successfully done. Staff satisfaction with the POC process was high. The POC-PCR testing in the emergency department is feasible and shows a very high diagnostic performance. Trial registration: DRKS00019207

9.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21267140

RESUMO

ObjectiveThe LIVE-AIR trial demonstrated that the anti-GM-CSF monoclonal antibody, lenzilumab improved the likelihood of survival without invasive mechanical ventilation (SWOV) in COVID-19 patients; with greatest effect in those with baseline CRP below the median baseline value of 79 mg/L. Similar to GM-CSF, C-reactive protein (CRP) levels are correlated with COVID-19 severity. This current analysis assessed the utility of baseline CRP levels to guide treatment with lenzilumab. DesignLIVE-AIR was a phase 3, double-blind, placebo-controlled trial. Participants were randomized 1:1 and stratified according to age and disease severity, to receive lenzilumab or placebo on Day 0, were followed through Day 28. SettingSecondary and tertiary care hospitals in the US and Brazil. Participants520 hospitalized COVID-19 participants with SpO2[≤] 94% on room air or required supplemental oxygen but not invasive mechanical ventilation were included. InterventionsLenzilumab (1800mg; divided as 3 doses, q8h) or placebo infusion alongside standard treatments including corticosteroids and remdesivir. Main outcome measuresA multi-variate logistic regression analysis assessed key baseline risk factors for progression to IMV or death. The primary endpoint, SWOV, and key secondary endpoints were analyzed according to baseline CRP levels in all participants with CRP values. ResultsThe multi-variate analysis demonstrated that elevated baseline plasma CRP was the most predictive feature for progression to IMV or death. SWOV was achieved in 152 (90%; 95%CI: 85to 94) lenzilumab and 183 (79%; 72 to 84) placebo participants with baseline CRP<150 mg/L and its likelihood was greater with lenzilumab than placebo (HR: 2.54; 95%CI, 1.46 to 4.41; p=0.0009) but not in participants with CRP[≥]150 mg/L at baseline. CRP as a covariate in the overall analysis demonstrated a statistically significant interaction with lenzilumab treatment (p=0.044). Grade [≥] 3 adverse events in participants with baseline CRP<150 mg/L were reported in 18% and 28% in lenzilumab or placebo, respectively. No treatment-emergent serious adverse events were attributable to lenzilumab. ConclusionThese finding suggest that COVID-19 participants with low baseline CRP levels achieve the greatest clinical benefit from lenzilumab and that baseline CRP levels may be a useful biomarker to guide therapeutic intervention. Trial RegistrationClinicalTrials.gov NCT04351152 WHAT IS ALREADY KNOWN ON THIS TOPICGM-CSF is one of the early upstream mediators and orchestrators of the hyperinflammatory immune response following SARS-CoV-2 infection. Baseline levels of GM-CSF and CRP have each been shown to correlate with COVID-19 disease progression. Increases in CRP are driven by elevations of IL-6 during the hyperinflammatory response following SARS-CoV-2 infection. In the phase 3, randomized, double-blind, placebo-controlled LIVE-AIR study, GM-CSF neutralization with lenzilumab significantly improved the likelihood of survival without invasive mechanical ventilation (SWOV, primary endpoint, also referred to as ventilator-free survival) vs. placebo (HR:1.54; 95% CI, 1.02 to 2.32; p=0.0403), which included standard supportive care including corticosteroids and remdesivir. No treatment-emergent serious adverse events attributable to lenzilumab have been reported to date. WHAT THIS STUDY ADDSA comprehensive analysis of LIVE -AIR CRP data provides evidence for the utility of baseline CRP to predict progression to IMV and death. Baseline CRP was identified to be the strongest predictor of SWOV in this study. Patients with baseline CRP<150 mg/L represented 78% of the study population and demonstrated the greatest clinical benefit with lenzilumab, including SWOV through day 28 (HR: 2.54; 95%CI; 1.46-4.41; nominal p=0.0009). A biomarker-driven approach using baseline CRP levels to guide therapeutic intervention may improve outcomes in those hospitalized with COVID-19. Participants with baseline CRP levels above 150 mg/L were described as experiencing COVID-19-associated hyperinflammation and were at risk of imminent escalation of respiratory support or death. Elevated baseline plasma CRP was the most predictive feature for progression to IMV or death (OR, 0.15; 95%CI, 0.07-0.29; nominal p<0.001). These findings suggest that baseline CRP may be a useful biomarker in determining which participants may be most successfully treated with lenzilumab.

10.
Flavio Azevedo Figueiredo; Lucas Emanuel Ferreira Ramos; Rafael Tavares Silva; Magda Carvalho Pires; Daniela Ponce; Rafael Lima Rodrigues de Carvalho; Alexandre Vargas Schwarzbold; Amanda de Oliveira Maurilio; Ana Luiza Bahia Alves Scotton; Andresa Fontoura Garbini; Barbara Lopes Farace; Barbara Machado Garcia; Carla Thais Candida Alves Silva; Christiane Correa Rodrigues Cimini Cimini; Cintia Alcantara de Carvalho; Cristiane dos Santos Dias; Daniel Vitorio Silveira; Euler Roberto Fernandes Manenti; Evelin Paola de Almeida Cenci; Fernando Anschau; Fernando Graca Aranha; Filipe Carrilho de Aguiar; Frederico Bartolazzi; Giovanna Grunewald Vietta; Guilherme Fagundes Nascimento; Helena Carolina Noal; Helena Duani; Heloisa Reniers Vianna; Henrique Cerqueira Guimaraes; Joice Coutinho de Alvarenga; Jose Miguel Chatkin; Julia Parreiras Drumond de Moraes; Juliana Machado Rugolo; Karen Brasil Ruschel; Karina Paula Medeiros Prado Martins; Luanna Silva Monteiro Menezes; Luciana Siuves Ferreira Couto; Luis Cesar de Castro; Luiz Antonio Nasi; Maderson Alvares de Souza Cabral; Maiara Anschau Floriani; Maira Dias Souza; Maira Viana Rego Souza e Silva; Marcelo Carneiro; Mariana Frizzo de Godoy; Maria Aparecida Camargos Bicalho; Maria Clara Pontello Barbosa Lima; Matheus Carvalho Alves Nogueira; Matheus Fernandes Lopes Martins; Milton Henriques Guimaraes-Junior; Natalia da Cunha Severino Sampaio; Neimy Ramos de Oliveira; Patricia Klarmann Ziegelmann; Pedro Guido Soares Andrade; Pedro Ledic Assaf; Petronio Jose de Lima Martelli; POLIANNA DELFINO PEREIRA; Raphael Castro Martins; Rochele Mosmann Menezes; Saionara Cristina Francisco; Silvia Ferreira Araujo; Talita Fischer Oliveira; Thainara Conceicao de Oliveira; Thais Lorenna Souza Sales; Yuri Carlotto Ramires; Milena Soriano Marcolino.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268631

RESUMO

Background: Acute kidney injury (AKI) is frequently associated with COVID-19 and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalized COVID-19 patients. Methods: This study is part of the multicentre cohort, the Brazilian COVID-19 Registry. A total of 5,212 adult COVID-19 patients were included between March/2020 and September/2020. We evaluated four categories of predictor variables: (1) demographic data; (2) comorbidities and conditions at admission; (3) laboratory exams within 24 h; and (4) the need for mechanical ventilation at any time during hospitalization. Variable selection was performed using generalized additive models (GAM) and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. The accuracy was assessed using the area under the receiver operating characteristic curve (AUCROC). Risk groups were proposed based on predicted probabilities: non-high (up to 14.9%), high (15.0 to 49.9%), and very high risk ([≥] 50.0%). Results: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalization. The validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. Thirty-two variables were tested and four important predictors of the need for KRT during hospitalization were identified using GAM: need for mechanical ventilation, male gender, higher creatinine at admission, and diabetes. The MMCD score had excellent discrimination in derivation (AUROC = 0.929; 95% CI 0.918-0.939) and validation (AUROC = 0.927; 95% CI 0.911-0.941) cohorts an good overall performance in both cohorts (Brier score: 0.057 and 0.056, respectively). The score is implemented in a freely available online risk calculator (https://www.mmcdscore.com/). Conclusion: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalized COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

11.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22269070

RESUMO

Abstract Recent evidence suggests that schizophrenia patients are at high risk for severe COVID-19 and should be prioritized for vaccination. However, impaired decision-making capacities could negatively affect the uptake of COVID-19 vaccination in this population. Competence to consent to COVID-19 vaccination was assessed in 80 outpatients with schizophrenia. Using the MacArthur Competence Assessment Tool for Treatment, 56.3% of the sample were classified as having diminished mental capacity. Poor performance was associated with lower vaccination rates, poorer cognition and higher level of psychotic symptoms. Developing interventions for enhancing informed consent for vaccination is urgent within this population.

12.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22269008

RESUMO

ImportanceResults from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data (IPD), including unanalyzed data from trials terminated early, enables further investigation of the efficacy and safety of HCQ/CQ. ObjectiveTo assess efficacy of HCQ/CQ in patients hospitalized with COVID-19, both overall and in prespecified subgroups. Data SourcesClinicalTrials.gov was searched multiple times in May-June 2020. Principal investigators of US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients were invited to collaborate in this IPD meta-analysis. Study SelectionRCTs in which: (1) HCQ/CQ was a treatment arm; (2) patient informed consent and/or individual study IRB approval allowed for data sharing; (3) principal investigators/their institutions signed a data use agreement for the present study; and (4) the outcomes defined in this study were recorded or could be extrapolated. Data Extraction and SynthesisWherever possible, harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator, then shared via a secure online data sharing platform to create a pooled data set. When this was not possible, individual study data were harmonized and merged manually. Data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Main Outcome(s) and Measure(s)7-point ordinal scale, measured between day 28 and 35 post-enrollment. ResultsEight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We found no evidence of a difference in ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions and RelevanceThe findings of this IPD meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients. Key PointsO_ST_ABSQuestionC_ST_ABSDoes hydroxychloroquine/chloroquine benefit hospitalized patients with COVID-19, overall or within prespecified subgroups? FindingsIn this individual participant data meta-analysis of 770 hospitalized COVID-19 patients across 8 clinical trials, we did not find evidence of a benefit of hydroxychloroquine/chloroquine, measured by a 7-point ordinal COVID-19 severity score at 28-35 days post-enrollment, in the pooled study population. We also found no substantial treatment effect heterogeneity among prespecified patient subgroups. MeaningThis study supports the consensus that hydroxychloroquine/chloroquine should not be used to treat hospitalized patients with COVID-19.

13.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268752

RESUMO

ObjectiveTo determine the impact of MS disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to SARS-CoV-2 infection. MethodsMS patients aged 18-60 were evaluated for anti-nucleocapsid and anti-Spike RBD antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture ELISA; and IL-2 and IFN{gamma} ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. ResultsBetween 1/6/2021 and 7/21/2021, 389 MS patients were recruited (mean age 40.3 years; 74% female; 62% non-White). Most common DMTs were ocrelizumab (OCR) - 40%; natalizumab - 17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. 177 patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, 47 - asymptomatic. Antibody responses were markedly attenuated in OCR compared to other groups (p[≤] 0001). T-cell responses (IFN{gamma} were decreased in S1P (p=0.03), increased in natalizumab (p<0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r=0.45, p=0.0002) and non-OCR (r=0.64, p<0.0001). Immune responses did not differ by race/ethnicity. COVID-19 clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized. InterpretationDMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and non-disabled group of MS patients.

14.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268991

RESUMO

A quantifiable model to describe the peaks and gaps during the several waves of COVID-19 is generated and applied to the progression of 120 countries. The number of waves encountered and how many more to be encountered is a question which is currently explored by all the scientific communities. In the same quest, an attempt has been made to quantitatively model the peaks and the gaps within them which have been encountered by 120 most affected countries from February 2020 - December 2021. These 120 countries were ranked based on the number of confirmed cases and deaths recorded during this period. This study further cluster these countries based on socio-economic and health interventions to find an association with three dependent features of COVID-19 i.e. number of confirmed cases, deaths and death-infectivity rate. The findings in this study suggests that, every wave had multiple peaks within them and as the number of peaks increased, predicting their growth rate or decline rate turns to be extremely difficult. However, considering the clusters which share the common features even with diverse countries, there is some possibility to predict what might be coming next. This study involves exhaustive analysis of reliable data which are available in open access and marks an important aspect to the COVID-19 research communities.

15.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268878

RESUMO

ObjectiveWe performed a meta-analysis in order to determine safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies on COVID-19. MethodsWe searched from the Cochrane Library, PubMed, Embase, biorxiv and medrxiv databases beginning in the COVID-19 outbreak on December 1, 2019 until August 29, 2021. The primary outcomes included death, the incidence of invasive mechanical ventilation (IMV), ventilation requirement, and secondary infection. Results6 eligible literature involving 1501 COVID-19 patients were recruited, and they were divided into experimental group (n = 736) and control group (n = 765). Using a random-effect model, we found that the GM-CSF antibodies treatment was associated with a 3.8-26.9% decline of the risk of mortality[odds ratio (OR) = 0.06, 95% confidence interval (CI): -0.11, -0.01, p =0.02], a 5.3-28.7% reduction of incidence of IMV [OR = 0.51, 95% CI: 0.28, 0.95, p =0.03], and a 23.3-50.0% enhancement of ventilation improvement [OR = 11.70, 95% CI: 1.99, 68.68, p=0.006]. There were no statistically significant differences in the association between two groups in second infection. ConclusionSevere COVID-19 patients may benefit from GM-CSF antibodies.

16.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21267956

RESUMO

Glycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glyco-isoform distributions of 597 abundant serum glycopeptides and non-glycosylated peptides in 50 individuals who had been seriously ill with COVID-19 and in 22 individuals who had recovered after an asymptomatic course of COVID-19. As additional comparison reference phenotypes, we included 12 individuals with a history of infection with a common cold coronavirus, 16 patients with bacterial sepsis, and 15 healthy subjects without history of coronavirus exposure. We found statistically significant differences, at FDR<0.05, for normalized abundances of 374 of the 597 peptides and glycopeptides interrogated, between symptomatic and asymptomatic COVID-19 patients. Similar statistically significant differences were seen when comparing symptomatic COVID-19 patients to healthy controls (350 differentially abundant peptides and glycopeptides) and common cold coronavirus seropositive subjects (353 differentially abundant peptides and glycopeptides). Among healthy controls and sepsis patients, 326 peptides and glycopeptides were found to be differentially abundant, of which 277 overlapped with biomarkers that showed differential expression between symptomatic COVID-19 cases and healthy controls. Among symptomatic COVID-19 cases and sepsis patients, 101 glycopeptide and peptide biomarkers were found to be statistically significantly abundant. Using both supervised and unsupervised machine learning techniques, we found specific glycoprotein profiles to be strongly predictive of symptomatic COVID-19 infection. LASSO-regularized multivariable logistic regression and K-means clustering yielded accuracies of 100% in an independent test set and of 96% overall, respectively. Our findings are consistent with the interpretation that a majority of glycoprotein modifications observed which are shared among symptomatic COVID-19 and sepsis patients likely represent a generic consequence of a severe systemic immune and inflammatory state. However, there are glyco-isoform changes that are specific and particular to severe COVID-19 infection. These may be representative of either COVID-19-specific consequences or of susceptibility to or predisposition for a severe course of the disease. Our findings support the potential value of glycoproteomic biomarkers in the biomedical understanding, and, potentially, the clinical management of serious acute infectious conditions.

17.
Clin Child Psychol Psychiatry ; : 13591045211061807, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984938

RESUMO

Background: Evidence indicates that the more traditional and behavioural parenting strategies are ineffective when parenting a child who has experienced developmental trauma. Recognising the need to parent with an attachment focus, the current paper evaluates the effectiveness of running the [Enfys] Nurturing Attachments Group, virtually, within the context of the COVID-19 pandemic. Method: A pilot feasibility study evaluated eight bespoke groups. Consenting professionals and co-professionals completed the Brief Parental Self-Efficacy Scale (BFSS), Care Questionnaire (CQ) and the Parental Reflective Functioning Questionnaire (PRFQ). Results: One hundred forty individuals attended the groups, with 51 (36%) completing both pre-and post-measures. The results provide evidence that professionals and co-professionals reported statistically significant positive increases on both the BPSS (d = .55) and CQ (d = .62). For the PRFQ, the results showed a statistically significant decrease on the Pre-mentalising sub scale, a non-significant mid-range score for Certainty about Mental States and a non-significant increase for Parental Interest and Curiosity in Mental States. Conclusion: The study has demonstrated initial viability of effectively facilitating the [Enfys] Nurturing Attachments Group, virtually. Importantly, it has also shown that the group can be run with professionals alongside co-professionals.

18.
PLoS Pathog ; 18(1): e1010171, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35025963

RESUMO

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.

19.
Anaesthesia ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35026055

RESUMO

One in four doctors in training in the UK reports feeling 'burnt out' due to their work and similar figures are reported in other countries. This two-group non-blinded randomised controlled trial aimed to determine if a novel text message intervention could reduce burnout and increase well-being in UK trainee anaesthetists. A total of 279 trainee anaesthetists (Core Training Year 2, Specialty Training Years 3 or 4) were included. All participants received one initial message sharing support resources. The intervention group (139 trainees) received 22 fortnightly text messages over approximately 10 months. Messages drew on 11 evidence-based themes including: gratitude; social support; self-efficacy; and self-compassion. Primary outcomes were burnout (Copenhagen Burnout Inventory) and well-being (Short Warwick-Edinburgh Mental Well-being Scale). Secondary outcomes were as follows: meaning in work; professional value; sickness absence; and consideration of career break. Outcomes were measured via online surveys. Measures of factors that may have affected well-being were included post-hoc, including the impact of COVID-19 (the first UK wave of which coincided with the second half of the trial). The final survey was completed by 153 trainees (74 in the intervention and 79 in the control groups). There were no significant group differences in: burnout (ß = -1.82, 95%CI -6.54-2.91, p = 0.45); well-being (-0.52, -1.73-0.69, p = 0.40); meaning (-0.09, -0.67-0.50, p = 0.77); value (-0.01, -0.67-0.66, p = 0.99); sick days (0.88, -2.08-3.83, p = 0.56); or consideration of career break (OR = 0.44, -0.30-1.18, p = 0.24). Exploratory post-hoc analysis found the intervention was associated with reduced burnout in participants reporting personal or work-related difficulties during the trial period (-9.56, -17.35 to -1.77, p = 0.02) and in participants reporting that the COVID-19 pandemic had a big negative impact on their well-being (-10.38, -20.57 to -0.19, p = 0.05). Overall, this trial found the intervention had no impact. However, given this intervention is low cost and requires minimal time commitment from recipients, it may warrant adaptation and further evaluation.

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