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1.
EClinicalMedicine ; 46:101373-101373, 2022.
Article in English | EuropePMC | ID: covidwho-1782304

ABSTRACT

Background There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes among patients with coronavirus COVID-19. This study aimed to synthesize the evidence on associations between the use of NSAIDs and adverse outcomes. Methods A systematic search of WHO COVID-19 Database, Medline, the Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to November 7, 2021, as well as a supplementary search of Google Scholar. We included all comparative studies that enrolled patients who took NSAIDs during the COVID-19 pandemic. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-analysis on the main adverse outcomes, as well as selected subgroup analyses stratified by the type of NSAID and population (both positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not). Findings Forty comparative studies evaluating 4,867,795 adult cases were identified. Twenty-eight (70%) of the included studies enrolled patients positive to SARS-CoV-2 tests. The use of NSAIDs did not reduce mortality outcomes among people with COVID-19 (number of studies [N] = 29, odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.75 to 1.14, I2 = 89%). Results suggested that the use of NSAIDs was not significantly associated with higher risk of SARS-CoV-2 infection in patients with or without COVID-19 (N = 10, OR = 0.96, 95% CI: 0.86 to 1.07, I2 = 78%;N = 8, aOR = 1.01, 95% CI: 0.94 to 1.09, I2 = 26%), or an increased probability of intensive care unit (ICU) admission (N = 12, OR = 1.28, 95% CI: 0.94 to 1.75, I2 = 82% ;N = 4, aOR = 0.89, 95% CI: 0.65 to 1.22, I2 = 60%), requiring mechanical ventilation (N = 11, OR = 1.11, 95% CI: 0.79 to 1.54, I2 = 63%;N = 5, aOR = 0.80, 95% CI: 0.52 to 1.24, I2 = 66%), or administration of supplemental oxygen (N = 5, OR = 0.80, 95% CI: 0.52 to 1.24, I2 = 63%;N = 2, aOR = 1.00, 95% CI: 0.89 to 1.12, I2 = 0%). The subgroup analysis revealed that, compared with patients not using any NSAIDs, the use of ibuprofen (N = 5, OR = 1.09, 95% CI: 0.50 to 2.39;N = 4, aOR = 0.95, 95% CI: 0.78 to 1.16) and COX-2 inhibitor (N = 4, OR = 0.62, 95% CI: 0.35 to 1.11;N = 2, aOR = 0.73, 95% CI: 0.45 to 1.18) were not associated with an increased risk of death. Interpretation Data suggests that NSAIDs such as ibuprofen, aspirin and COX-2 inhibitor, can be used safely among patients positive to SARS-CoV-2. However, for some of the analyses the number of studies were limited and the quality of evidence was overall low, therefore more research is needed to corroborate these findings. Funding There was no funding source for this study.

2.
BMC Med Res Methodol ; 22(1): 89, 2022 Apr 03.
Article in English | MEDLINE | ID: covidwho-1770484

ABSTRACT

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.


Subject(s)
COVID-19 , COVID-19/epidemiology , Child , Disease Outbreaks , Guidelines as Topic , Humans , Public Health
3.
BMC Gastroenterol ; 22(1): 113, 2022 Mar 09.
Article in English | MEDLINE | ID: covidwho-1736342

ABSTRACT

BACKGROUND: Most patients with coronavirus disease 2019 demonstrate liver function damage. In this study, the laboratory test data of patients with moderate coronavirus disease 2019 were used to establish and evaluate an early prediction model to assess the risk of liver function damage. METHODS: Clinical data and the first laboratory examination results of 101 patients with moderate coronavirus disease 2019 were collected from four hospitals' electronic medical record systems in Jilin Province, China. Data were randomly divided into training and validation sets. A logistic regression analysis was used to determine the independent factors related to liver function damage in patients in the training set to establish a prediction model. Model discrimination, calibration, and clinical usefulness were evaluated in the training and validation sets. RESULTS: The logistic regression analysis showed that plateletcrit, retinol-binding protein, and carbon dioxide combining power could predict liver function damage (P < 0.05 for all). The receiver operating characteristic curve showed high model discrimination (training set area under the curve: 0.899, validation set area under the curve: 0.800; P < 0.05). The calibration curve showed a good fit (training set: P = 0.59, validation set: P = 0.19; P > 0.05). A decision curve analysis confirmed the clinical usefulness of this model. CONCLUSIONS: In this study, the combined model assesses liver function damage in patients with moderate coronavirus disease 2019 performed well. Thus, it may be helpful as a reference for clinical differentiation of liver function damage. Trial registration retrospectively registered.


Subject(s)
COVID-19 , Humans , Liver , Nomograms , Retrospective Studies , Risk Factors , SARS-CoV-2
4.
Eur J Pediatr ; 2022 Feb 22.
Article in English | MEDLINE | ID: covidwho-1699807

ABSTRACT

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325364

ABSTRACT

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes in COVID-19 patients. Therefore, this study aimed to synthesize the existing evidence on associations between the use of NSAIDs and adverse outcomes among patients with COVID-19.Methods: Systematic search of WHO COVID-19 Database, Medline, The Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to August 10, 2021, as well as a supplementary search of Google Scholar. We included comparative observational studies and randomized controlled trials that enrolled patients with COVID-19 who took NSAIDs before or after diagnosis of COVID-19. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-anlysis on the main outcomes, as well as selected subgroup analyses stratified by the type of NSAID.Fingings: Fifteen non-randomized studies evaluating 24700 adult COVID-19 patients were identified. The use of NSAIDs in patients with COVID-19, compared with no use of NSAIDs, was not significantly associated with an elevated mortality (odds ratio [OR]=0.94, 95% confidence interval [CI]: 0.87 to 1.02), or an increased probability of ICU admission (OR=1.35, 95% CI: 0.73 to 2.49), requiring mechanical ventilation (OR=1.23, 95% CI: 0.71 to 2.13), or administration of supplemental oxygen (OR=0.99, 95% CI: 0.91 to 1.08). The subgroup analyses revealed that the use of ibuprofen (OR=1.22, 95% CI: 0.32 to 4.60), etoricoxib (OR=0.36, 95% CI: 0.02 to 6.49) or celecoxib (zero deaths in both groups) were not associated with an increased risk of death in COVID-19 patients, compared with not using any NSAID.Interpretation: Fever is one of the main clinical symptoms of COVID-19. According to our findings, NSAIDs such as ibuprofen can be used to treat fever in COVID-19 patients safely.Funding: None to declare. Declaration of Interest: None to declare.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323849

ABSTRACT

Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace. Here we describe rational antigen design through to manufacturability and vaccine efficacy, of a prefusion-stabilised Spike (S) protein, Sclamp. This strategy uses an orthogonal stabilisation approach compared to canonical vaccines, in combination with the licensed adjuvant MF59 (Seqirus). In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease, and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. The Sclamp vaccine candidate is currently completing Phase 1 clinical evaluation, in parallel with large-scale commercial manufacture for pivotal efficacy trials and potential widespread distribution.Funding: This work was funded by CEPI.Conflict of Interest: K.J.C., D.W. and P.R.Y. are inventors of the “Molecular Clamp” patent, US 2020/0040042.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323848

ABSTRACT

Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace with more than 30 candidate vaccines now in clinical evaluation. Here we describe the preclinical development of an adjuvanted, prefusion-stabilised Spike (S) protein “Sclamp” subunit vaccine, from rational antigen design through to assessing manufacturability and vaccine efficacy. In mice, the vaccine candidate elicits high levels of neutralising antibodies to epitopes both within and outside the receptor binding domain (RBD) of S, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells. We also show protection in Syrian hamsters, which has emerged as a robust animal model for pulmonary SARS-CoV-2 infection. No evidence of vaccine enhanced disease was observed in animal challenge studies and pre-clinical safety was further demonstrated in a GLP toxicology study in rats. The Sclamp vaccine candidate is currently progressing rapidly through clinical evaluation in parallel with large-scale manufacture for pivotal efficacy trials and potential widespread distribution.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321377

ABSTRACT

Background: The prognosis of children and adolescents with COVID-19 obtain increasing attention worldwide. This study provides the first systematic review and meta-analysis to identify risk factors which predict poor prognosis in this group.Methods: Electronic databases from inception to March, 2021 were searched for cohort studies, case-control studies and case series that investigated risk factors for poor prognosis of children and adolescents with COVID-19. We estimated the summary effect size by use of random-effects models and the 95% confidential interval (CI).Findings: We identified 33 studies, comprising 32,225 individuals. The risk of bias were generally high. In children and adolescents with COVID-19, risk of death was significantly increased in patients with MIS-C complication (odds ratio [OR]=58.00, 95% CI 6.39 to 526.79) and in need for intensive care (OR=15.25, 95% CI 1.98 to 117.44). Congenital heart disease (OR=2.90, 95% CI 1.26 to 6.67), chronic pulmonary disease (OR=3.45, 95% CI 1.47 to 8.07), and gastrointestinal symptoms (OR=2.11, 95% CI 1.43 to 3.12) increased the odds to be admitted to ICU;MIS-C complication (OR=70.00, 95% CI 6.51 to 752.27) and neurological diseases (OR=2.51, 95% CI 1.03 to 6.15) increased the odds of respiratory support;neurological diseases (OR=4.59, 95% CI 1.99 to 10.61), obesity (OR=2.51, 95% CI 2.02 to 3.12), C-reactive protein (CRP) level ≥80mg/L (OR=11.70, 95% CI 4.37 to 31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76 to 236.44) on admission increased the odds of progression to severe/critical disease.Interpretation: Very low to moderate quality evidence found that MIS-C, congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, and gastrointestinal symptoms, in need for intensive care, elevated CRP and D-dimer are risk factors for poor prognosis in children and adolescents with COVID-19.Funding: None.Declaration of Interests: The authors declare that they have no competing interests.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318615

ABSTRACT

Background: To explore the changes in lymphocyte subsets and cytokine profiles in patients with coronavirus disease 2019 (COVID-19) and their relationship with disease severity. Methods: : This study included 228 patients with COVID-19 who were treated at Chongqing University Three Gorges Hospital from January 1, 2020 to February 20, 2020. The characteristics of lymphocyte subsets and cytokine profiles of severe and mild COVID-19 patients were compared. Of the 228 patients enrolled, 48 were severe patients and 180 were mild patients. Results: : Lymphocyte counts, absolute number of total T lymphocytes, CD 4+ T cells, CD 8+ T cells, and total B lymphocytes were significantly lower in severe patients (0.8×10 9 /L, 424.5×10 6 /L, 266×10 6 /L, 145.5×10 6 /L, 109.5×10 6 /L, respectively) than in mild patients (1.2×10 9 /L, 721×10 6 /L, 439.5×10 6 /L, 281.5×10 6 /L, 135×10 6 /L, respectively). A multivariate logistic regression analysis showed that age, C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) were independent risk factors for developing into severe condition. The lymphocyte subsets decreased and cytokine profiles increased more significantly in severe patients than in mild patients. Conclusions: : CRP, NLR, and age may serve as powerful factors for early identification of severe patients.

10.
J Clin Epidemiol ; 144: 163-172, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1670681

ABSTRACT

OBJECTIVE: To describe the current status of COVID-19 vaccine guidelines. STUDY DESIGN AND SETTING: We searched databases, Google and guideline platforms to retrieve COVID-19 vaccine guidelines published between January 1, 2020 and July 8, 2021. We worked in pairs to identify the eligible guidelines and extract data of whether the methodology, funding, and conflict of interests were assessed/reported, and so on. Results were presented descriptively. RESULTS: A total of 106 COVID-19 vaccine guidelines were included. In the first half of 2021, on average 15 guidelines were published every month. Fifty (47.2%) guidelines addressed the vaccination of people with specific medical conditions, and 18 (17.0%) guidelines focused on adverse effects after vaccination. Only 28 (26.4%) guidelines reported the methodology they used. Four (3.8%) of guidelines assessed both the quality of evidence and strength of recommendations; 42 (39.6%) and 65 (61.3%) guidelines reported their funding sources and conflict of interest, respectively. Most guidelines were published in English (n = 92, 86.8%). CONCLUSION: A high number of guidelines on COVID-19 vaccines have been published in the recent months, but most of them lack clear and transparent reporting of methodology, funding, and conflicts of interest. Rigorous methodological and reporting quality evaluation of these guidelines is needed.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Databases, Factual , Humans
11.
Nat Cell Biol ; 23(12): 1314-1328, 2021 12.
Article in English | MEDLINE | ID: covidwho-1559292

ABSTRACT

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments.


Subject(s)
COVID-19/genetics , Lung/metabolism , Transcriptome/genetics , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , COVID-19/metabolism , Fibrosis/metabolism , Fibrosis/pathology , Fibrosis/virology , Humans , Lung/pathology , Lung/virology , Proteomics/methods , SARS-CoV-2/pathogenicity
12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292232

ABSTRACT

Introduction: The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. Methods: : We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. Results: : A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 54.7% (95%CI, 10.3% to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2% to 10.1%) died, 27.0% (95%CI, 0% to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. Conclusions: : Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

13.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5117-5122, 2021 Oct.
Article in Chinese | MEDLINE | ID: covidwho-1485611

ABSTRACT

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.


Subject(s)
COVID-19/therapy , China , Evidence-Based Medicine , Humans , Medicine, Chinese Traditional , Practice Guidelines as Topic , SARS-CoV-2
14.
EClinicalMedicine ; 41: 101155, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1471950

ABSTRACT

BACKGROUND: This study provides the first systematic review and meta-analysis to identify the predictors of unfavorable prognosis of COVID-19 in children and adolescents. METHODS: We searched literature databases until July 2021 for studies that investigated risk factors for unfavorable prognosis of children and adolescents with COVID-19. We used random-effects models to estimate the effect size with 95% confidence interval (CI). FINDINGS: We identified 56 studies comprising 79,104 individuals. Mortality was higher in patients with multisystem inflammatory syndrome (MIS-C) (odds ratio [OR]=58.00, 95% CI 6.39-526.79) and who were admitted to intensive care (OR=12.64, 95% CI 3.42-46.68). Acute respiratry distress syndrme (ARDS) (OR=29.54, 95% CI 12.69-68.78) and acute kidney injury (AKI) (OR=55.02, 95% CI 6.26-483.35) increased the odds to be admitted to intensive care; shortness of breath (OR=16.96, 95% CI 7.66-37.51) increased the need of respiratory support; and neurological diseases (OR=5.16, 95% CI 2.30-11.60), C-reactive protein (CRP) level ≥80 mg/L (OR=11.70, 95% CI 4.37-31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76-236.44) increased the odds of progression to severe or critical disease. INTERPRETATION: Congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, MIS-C, shortness of breath, ARDS, AKI, gastrointestinal symptoms, elevated CRP and D-dimer are associated with unfavourable prognosis in children and adolescents with COVID-19.

15.
J Evid Based Med ; 14(4): 313-332, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1462829

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , China , Humans , Medicine, Chinese Traditional , Pandemics , Practice Guidelines as Topic , SARS-CoV-2
17.
Crystals ; 11(8):997, 2021.
Article in English | MDPI | ID: covidwho-1367799

ABSTRACT

The global battle against the COVID-19 pandemic relies strongly on the human defense of antibody, which is assumed to bind the antigen’s receptor binding domain (RBD) with its hypervariable region (HVR). Due to the similarity to other viruses such as SARS, however, our understanding of the antibody-virus interaction has been largely limited to the genomic sequencing, which poses serious challenges to containment and rapid serum testing. Based on the physical/chemical nature of the interaction, infrared spectroscopy was employed to reveal the binding disparity, the real cause of the antibody-virus specificity at the molecular level, which is inconceivable to be investigated otherwise. Temperature dependence was discovered in the absorption value from the 1550 cm−1 absorption band, attributed to the hydrogen bonds by carboxyl/amino groups, binding the SARS-CoV-2 spike protein and closely resembled SARS-CoV-2 or SARS-CoV-1 antibodies. The infrared absorption intensity, associated with the number of hydrogen bonds, was found to increase sharply between 27 °C and 31 °C, with the relative absorbance matching the hydrogen bonding numbers of the two antibody types (19 vs. 12) at 37 °C. Meanwhile, the ratio of bonds at 27 °C, calculated by thermodynamic exponentials, produces at least 5% inaccuracy. Beyond genomic sequencing, the temperature dependence, as well as the bond number match at 37 °C between relative absorbance and the hydrogen bonding numbers of the two antibody types, is not only of clinical significance in particular but also as a sample for the physical/chemical understanding of vaccine–antibody interactions in general.

18.
19.
Ann Transl Med ; 9(8): 633, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1227244

ABSTRACT

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic negatively affects children's health. Many guidelines have been developed for treating children with COVID-19. The quality of the existing guidelines and the consistency of recommendations remains unknown. Therefore, we aim to review the clinical practice guidelines (CPGs) for children with COVID-19 systematically. METHODS: We systematically searched Medline, Embase, guideline-related websites, and Google. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist were used to evaluate the methodological and reporting quality of the included guidelines, respectively. The consistency of recommendations across the guidelines and their supporting evidence were analyzed. RESULTS: Twenty guidelines were included in this study. The mean AGREE II score and mean RIGHT reporting rate of the included guidelines were 37% (range, 22-62%) and 52% (range, 31-89%), respectively. As for methodological quality, no guideline was classified as high, one guideline (5%) moderate, and 19 (95%) low. In terms of reporting quality, one guideline (5%) was rated as high, 12 guidelines (60%) moderate, and seven (35%) low. Among included guidelines, recommendations varied greatly in the use of remdesivir (recommend: 25%, not recommend: 45%, not report: 30%), interferon (recommend: 15%, not recommend: 50%, not report: 35%), glucocorticoids (recommend: 50%, not recommend: 20%, not report: 30%), and intravenous immune globulin (recommend: 35%, not recommend: 30%, not report: 35%). None of the guidelines cited clinical trials from children with COVID-19. CONCLUSIONS: The methodological and reporting quality of guidelines for treating children with COVID-19 was not high. Recommendations were inconsistent across different guidelines. The supporting evidence from children with COVID-19 was very limited.

20.
J Med Virol ; 93(4): 2115-2131, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217370

ABSTRACT

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) urgently requires an effective vaccine for prevention. In this study, 66 epitopes containing pentapeptides of SARS-CoV-2 spike protein in the IEDB database were compared with the amino acid sequence of SARS-CoV-2 spike protein, and 66 potentially immune-related peptides of SARS-CoV-2 spike protein were obtained. Based on the single-nucleotide polymorphisms analysis of spike protein of 1218 SARS-CoV-2 isolates, 52 easily mutated sites were identified and used for vaccine epitope screening. The best vaccine candidate epitopes in the 66 peptides of SARS-CoV-2 spike protein were screened out through mutation and immunoinformatics analysis. The best candidate epitopes were connected by different linkers in silico to obtain vaccine candidate sequences. The results showed that 16 epitopes were relatively conservative, immunological, nontoxic, and nonallergenic, could induce the secretion of cytokines, and were more likely to be exposed on the surface of the spike protein. They were both B- and T-cell epitopes, and could recognize a certain number of HLA molecules and had high coverage rates in different populations. Moreover, epitopes 897-913 were predicted to have possible cross-immunoprotection for SARS-CoV and SARS-CoV-2. The results of vaccine candidate sequences screening suggested that sequences (without linker, with linker GGGSGGG, EAAAK, GPGPG, and KK, respectively) were the best. The proteins translated by these sequences were relatively stable, with a high antigenic index and good biological activity. Our study provided vaccine candidate epitopes and sequences for the research of the SARS-CoV-2 vaccine.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/virology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Sequence , Computational Biology , Humans , Immunogenicity, Vaccine
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