Ostracizing Children from Research in COVID-19: Is it Ethical?
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ABSTRACT:
SUBMITTER: Meena J
PROVIDER: S-EPMC7543960 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Ostracizing Children from Research in COVID-19: Is it Ethical?
Meena Jitendra J Yadav Arushi A Kumar Jogender J
Indian journal of pediatrics 20201008 3
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Project description:ObjectivesIn response to the COVID-19 pandemic there have been significant developments in research, its conduct and the supporting ethical framework. While many protocols have been delayed, halted or modified, other research efforts have been accelerated, generating controversy. The goal of this paper is to determine the rates of references surrounding the ethical oversight of research as reported in current COVID-19-related research publications.DesignScoping review.SettingPopulation-based observational or interventional studies from December 2019 to May 2020 with sample size of two or more. Studies were searched through electronic databases including Medline, EMBASE, and Cochrane CENTRAL Register of Controlled Trials.ParticipantsEligibility criteria included participants within published studies who tested positive for COVID-19.Main outcomes and measuresData were extracted and charting methods included taking note of references to ethical frameworks, institutional review board (IRB), ethics committee (EC) or research ethics board (REB) involvement, consent processes, and other variables.Results11 556 articles were screened, with 656 included in the final analysis. References to ethics were present in 530 (80.8%) studies, with 491 (74.8%) involving IRB/ECs/REBs and 126 (19.2%) not referencing ethics. Consent processes were outlined in 201 (30.6%) studies, with 198 (30.2%) reporting that they obtained consent waivers, however, 257 (39.2%) did not mention consent at all. Differences (p<0.001) in ethics-related references were apparent when analysed by continent, publication type, sample size and IF.ConclusionsThe majority of published articles pertaining to COVID-19 research made mention of ethical considerations, however, national and regional variations in research ethics review requirements introduce heterogeneity between studies and raise important questions about the conduct of scientific research during global public emergencies.Trial registration numberOpen Science Framework: https://osfio/z67wb.
| S-EPMC8313312 | biostudies-literature
Project description:Purpose: This study aims to characterize the early innate and adaptive responses induced by SARS-CoV-2 infection in children and adults over time up to 8 weeks post symptoms onset (POS). We report the gene signature of COVID-19 over the course of the disease in both age groups. The kinetic of infection was divided in 5-time intervals according to the calculated days POS: interval 1 (0-5), interval 2 (6-14), interval 3 (15-22), interval 4 (23-35), and interval 5 (36-81). Methods: RNA extraction was performed automatically via the PAXgene Blood miRNA Kit and the QIAcube instrument (Qiagen) following the manufacturer’s protocol. RNA concentration and quality were assessed by using the Qubit instrument (Invitrogen) and the Agilent 2100 Bioanalyzer, respectively. The Stranded Total RNA Ribo-Zero Plus kit from Illumina was used for the library preparation with 100 ng of total RNA as input. Library molarity and quality were assessed with the Qubit and Tapestation using a DNA High sensitivity chip (Agilent Technologies). Libraries were pooled at 2 nM for clustering and sequenced on an Illumina HiSeq 4000 sequencer for a minimum of 30 million single-end 100 reads per sample. Main results: (I) we observed an antiviral-IFN-signature and innate-cell-activation within the first 5 days post symptoms onset (POS), while genes associated with CD4 T-cell responses, plasma cells and immunoglobulin were upregulated in both age groups during the first two weeks POS, indicative of SARS-CoV-2-specific adaptive immune responses; (II) in adults, genes associated with IFN antiviral responses and activated dendritic cells were maintained during the second week of disease, and subsided only after 14 days. By contrast, those transcriptome changes subsided already after 5 days in children.
2021-09-22 | GSE166190 | GEO
Project description:BACKGROUND. Coronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease. METHODS. Clinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti–SARS-CoV-2 IgG and IgA were quantified in nasal fluid. We used a subset of 21 samples for RNAseq analysis. RESULTS. SARS-CoV-2 copies, angiotensin-converting enzyme 2 (ACE2), and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti–SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died. CONCLUSION. These findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.
2021-05-11 | GSE172274 | GEO
Project description:BackgroundDuring the beginning of the COVID-19 pandemic there was an urgent need for accelerated review of COVID-19 research by Medical Research Ethics Committees (MRECs). In the Netherlands this led to the implementation of so-called 'fast-track-review-procedures' (FTRPs) to enable a swift start of urgent and relevant research. The objective of this study is to evaluate FTRPs of MRECs in the Netherlands during the COVID-19 pandemic and to compare them with the regular review procedures (RRPs).Methods and findingsAn explanatory sequential mixed method study was conducted. Online questionnaires and four group interviews were conducted among MREC representatives and investigators of COVID-19 research. In addition, data from a national research registration system was requested. Main outcome measures are differences in timelines, quality of the review and satisfaction between FTRPs and RRPs. The total number of review days was shorter in FTRP (median 10.5) compared to RRPs (median 98.0). Review days attributable to the MRECs also declined in FTRPs (median 8.0 versus 50.0). This shortening can be explained by installing ad hoc (sub)committees, full priority given to COVID-19 research, regular research put on hold, online review meetings and administrative leniency. The shorter timelines did not affect the perceived quality of the review and ethical and legal aspects were not weighted differently. Both MREC representatives and investigators were generally satisfied with the review of COVID-19 research. Weaknesses identified were the lack of overview of COVID-19 research and central collaboration and coordination, the delay of review of regular research, and limited reachability of secretariats.ConclusionsThis study shows that accelerated review is feasible during emergency situations. We did not find evidence that review quality was compromised and both investigators and MRECs were content with the FTRP. To improve future medical ethical review during pandemic situations and beyond, distinguishing main and side issues, working digitally, and (inter)national collaboration and coordination are important.
| S-EPMC8301608 | biostudies-literature
Project description:COVID-19 poses an extraordinary threat to global public health and an effective vaccine could provide a key means of overcoming this crisis. Human challenge studies involve the intentional infection of research participants and can accelerate or improve vaccine development by rapidly providing estimates of vaccine safety and efficacy. Human challenge studies of low virulence coronaviruses have been done in the past and human challenge studies with severe acute respiratory syndrome coronavirus 2 have been proposed. These studies of coronaviruses could provide considerable benefits to public health; for instance, by improving and accelerating vaccine development. However, human challenge studies of severe acute respiratory syndrome coronavirus 2 in particular might be controversial, in part, for ethical reasons. The ethical issues raised by such studies thus warrant early consideration involving, for example, broad consultation with the community. This Personal View provides preliminary analyses of relevant ethical considerations regarding human challenge studies of severe acute respiratory syndrome coronavirus 2, including the potential benefits to public health and to participants, the risks and uncertainty for participants, and the third-party risks (ie, to research staff and the wider community). We argue that these human challenge studies can reasonably be considered ethically acceptable insofar as such studies are accepted internationally and by the communities in which they are done, can realistically be expected to accelerate or improve vaccine development, have considerable potential to directly benefit participants, are designed to limit and minimise risks to participants, and are done with strict infection control measures to limit and reduce third-party risks.
| S-EPMC7259898 | biostudies-literature
Project description:Several humanized ACE2 (hACE2) mouse models have been developed for COVID-19 studies. Insertion of hACE2 at mouse Ace2 locus enables the utilization of endogenous promoter to drive its expression, better reflecting ACE2 abundance in various cell types and tissues. However, the relatively low expression of hACE2 in these mice may limit their fidelity in mimicking COVID-19 manifestations in humans and hinder their application in viral studies. In this study, we generated four hACE2 mouse models using different strategies for hACE2 expression. We found that the position of the β-globin intron within hACE2 cassette could have contrasting effects on hACE2 expression, with its placement downstream of hACE2 significantly increasing its transcription. Western blot analysis demonstrated that optimizing hACE2 codon usage further enhanced translation efficiency from all tested tissue. Consistent with elevated hACE2 expression, opt-hACE2 mice displayed more active immune response and severe COVID-19 phenotypes following SARS-CoV-2 challenging compared to other hACE2 mouse models. Thus, our study has elucidated the dual role of β-globin element in transgene expression, and highlighted that mice with optimized hACE2 codon preference could serve as a better model for SARS-CoV-2 studies.
2025-02-12 | GSE271163 | GEO
Project description:BackgroundIn the course of the COVID-19 pandemic, the biomedical research community's attempt to focus the attention on fighting COVID-19, led to several challenges within the field of research ethics. However, we know little about the practical relevance of these challenges for Research Ethics Committees (RECs).MethodsWe conducted a qualitative survey across all 52 German RECs on the challenges and potential solutions with reviewing proposals for COVID-19 studies. We de-identified the answers and applied thematic text analysis for the extraction and synthesis of challenges and potential solutions that we grouped under established principles for clinical research ethics.ResultsWe received an overall response rate of 42%. The 22 responding RECs reported that they had assessed a total of 441 study proposals on COVID-19 until 21 April 2020. For the review of these proposals the RECs indicated a broad spectrum of challenges regarding (1) social value (e.g. lack of coordination), (2) scientific validity (e.g. provisional study planning), (3) favourable risk-benefit ratio (e.g. difficult benefit assessment), (4) informed consent (e.g. strict isolation measures), (5) independent review (e.g. lack of time), (6) fair selection of trial participants (e.g. inclusion of vulnerable groups), and (7) respect for study participants (e.g. data security). Mentioned solutions ranged from improved local/national coordination, over guidance on modified consent procedures, to priority setting across clinical studies.ConclusionsRECs are facing a broad spectrum of pressing challenges in reviewing COVID-19 studies. Some challenges for consent procedures are well known from research in intensive care settings but are further aggravated by infection measures. Other challenges such as reviewing several clinical studies at the same time that potentially compete for the recruitment of in-house COVID-19 patients are unique to the current situation. For some of the challenges the proposed solutions in our survey could relatively easy be translated into practice. Others need further conceptual and empirical research. Our findings together with the increasing body of literature on COVID-19 research ethics, and further stakeholder engagement should inform the development of hands-on guidance for researchers, funders, RECs, and further oversight bodies.
| S-EPMC8287116 | biostudies-literature
Project description:Introduction: Vaccines and drugs for the treatment and prevention of COVID-19 require robust evidence generated from clinical trials before they can be used. Decisions on how to apply non-pharmaceutical interventions such as quarantine, self-isolation, social distancing and travel restrictions should also be based on evidence. There are some experiential and mathematical modelling data for these interventions, but there is a lack of data on the social, ethical and behavioural aspects of these interventions in the literature. Therefore, our study aims to produce evidence to inform (non-pharmaceutical) interventions such as communications, quarantine, self-isolation, social distancing, travel restrictions and other public health measures for the COVID-19 pandemic. Methods: The study will be conducted in the United Kingdom, Italy, Malaysia and Thailand. We propose to conduct 600-1000 quantitative surveys and 25-35 qualitative interviews per country. Data collection will follow the following four themes: (1) Quarantine and self-isolation (2) social distancing and travel restrictions (3) wellbeing and mental health (4) information, misinformation and rumours. In light of limitations of travel and holding in-person meetings, we will use online/remote methods for collecting data. Study participant will be adults who have provided informed consent from different demographic, socio-economic and risk groups. Discussion: At the time of writing, United Kingdom, Italy, Malaysia and Thailand have initiated strict public health measures and varying degrees of "lockdowns" to curb the pandemic. It is anticipated that these public health measures will continue in some countries (e.g. Italy, Malaysia) or be tightened further in other countries (e.g. Thailand, UK) to control the spread of the disease in the coming weeks and months. The data generated from our study could inform these strategies in real time.
| S-EPMC7355217 | biostudies-literature
Project description:Background: COVID-19 has infected more than 100-million worldwide. Children appear less susceptible to COVID-19 and present with milder symptoms. Cases of children with COVID-19 developing clinical features of Kawasaki-disease have been described. Methods: We utilised SWATH-MS proteomics to determine the plasma proteins expressed in healthy children, children with multisystem inflammatory syndrome (MIS-C) and children with COVID-19 induced ARDS. Pathway analyses were performed to determine the affected pathways. Results: 76 proteins were differentially expressed across the groups, with 85 and 52 proteins specific to MIS-C and COVID-19 ARDS. Complement and coagulation activation were implicated in these clinical phenotypes, however there was contribution of FcGR and BCR activation in MIS-C and scavenging of heme and retinoid metabolism in COVID-19 ARDS. Conclusions: We show proteome differences in MIS-C and COVID-ARDS, although both show complement and coagulation dysregulation. The results may be helpful in developing therapeutic targets that could improve the outcomes for these children.
2022-04-06 | PXD025125 | Pride
Project description:Multisystem Inflammatory Syndrome in Children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by SARS-CoV-2 antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism, distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that the hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.
2022-11-05 | GSE217370 | GEO