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3.
authorea preprints; 2024.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.170669909.92042889.v1

ABSTRACT

Background: COVID-19, which occurred at the end of December 2019, has evolved into a global public health threat. COVID-19’s high infectivity and mortality prompt governments and scientific community to respond quickly to the outbreak of the pandemic. The application of personal protective equipment (PPE) is of great significance in overcoming the epidemic situation. Although there were many studies about PPE and COVID-19, there is no study about bibliometric analysis of these studies. This study aims to provide a general overview of studies on PPE and COVID-19. Methods: On October 07, 2021, the Web of Science (WOS) Core Collection database was used to identify documents on PPE and COVID-19. HistCite and VOSviewer softwares were used for citation analysis and visualization mapping. Results: A total of 1462 documents authored by 6993 authors and published in 750 journals were included in the final analysis. The most prolific author was Macintyre CR. The USA was the most productive country with 463 published documents. The leading journal was Plos One. Network visualization map showed that USA was the largest international collaboration network. The keyword “COVID-19” had the strongest total link strengths (TLS) and largest number of occurrences. The New England Journal of Medicine was the leading source with highest TLS. The University of Toronto had the highest number of links and the highest TLS. Conclusions: The bibliometric analysis of PPE and COVID-19 provides an overall perspective, and the appreciation and study of these influential publications are very useful for future research.


Subject(s)
COVID-19
4.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.12.06.23299623

ABSTRACT

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B*15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the US (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B*15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified. These findings suggest that memory T-cell immunity to seasonal coronaviruses does not strongly influence the outcome of SARS-CoV-2 infection in unvaccinated individuals.


Subject(s)
COVID-19 , Pneumonia , Infections
5.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3674274.v1

ABSTRACT

Background Since the outbreak of the COVID-19 epidemic, many public health issues have arisen. However, based on bibliometric analyses, little attention has been paid to overall trends in this area. This study sought to describe the status of public health events in the COVID-19 pandemic using systematic review of high-quality research evidence, thereby revealing the trend of public health during COVID-19, research hotspots, and provide lessons and references for future research in the field of public health emergencies.Methods Co-Occurrence and VOSviewer bibliometric methods were used to analyze the literature related to the public health during COVID-19 in the Web of Science (WOS) core database. The public health characteristics during the COVID-19 pandemic were explored by analyzing the number of publications, countries, institutions, and keywords.Results This study included 1911 original research articles and reviews in English on public health issues during the pandemic. The United States, China, and England are the main forces in this field, and they collaborate closely with each other. Research institutions in each country are dominated by universities, with the University of Toronto being the most productive institution in the world. The authors with most publications are Larson, Looi, and Neumark-sztainer. Visual analysis shows that the main focus of research are characteristics of the COVID-19 pandemic, problems encountered by Citizens during the COVID-19 pandemic and responses to Public Health issues during the COVID-19 pandemic.Conclusions These results reveal emerging research on public health issues during the COVID-19 pandemic, especially the impacts caused by the pandemic on public health determinants.


Subject(s)
COVID-19
7.
Traditional Medicine Research ; 8(6):1-20, 2023.
Article in English | Academic Search Complete | ID: covidwho-2297182

ABSTRACT

Background: As of 2023, coronavirus disease 2019 (COVID-19) is still spreading globally. Therefore, we aim to integrate non-critical COVID-19 high-frequency and high-targeting Chinese medicines to provide a reference for clinical prescriptions to improve COVID-19-related symptoms. Materials and methods: The information on non-critical COVID-19 high-frequency Chinese medicines in the diagnosis and treatment of COVID-19 was obtained by the TCM inheritance support platform. Using network pharmacology and molecular docking technology, high-targeting Chinese medicines with good docking activity with COVID-19 receptors angiotensin-converting enzyme-II (ACE2), 3CLpro and tyrosine-protein kinase receptor UFO (AXL) were obtained. A new prescription for non-critical COVID-19 was established by integrating high-frequency and high-targeting Chinese medicines. Rats with acute lung injury induced by lipopolysaccharide were used as the experimental model. The histopathological changes in the lungs of rats in each group were observed by hematoxylin-eosin staining. The lung coefficient of rats was measured. The levels of IL-6, TNF-a, and IL-1ß in serum were detected by enzyme-linked immunosorbent assay. The mRNA and protein levels of ACE2 and AXL in lung tissue were detected by real-time quantitative polymerase chain reaction and western blot. Results: Through data mining, it was found that there were 39 high-frequency traditional Chinese medicines for non-critical COVID-19 in the diagnosis and treatment guidelines. According to network pharmacology and molecular docking, 30 highly targeted traditional Chinese drugs for COVID-19 were found. The new prescriptions for non-critical COVID-19 were comprehensively obtained, including Glycyrrhizae Radix, Ephedra Herba, Amygdalus Communis Vas, Gypsum Fibrosum, Descurainiae Semen, Atractylodes Lancea, Scutellariae Radix, Amomum Tsao-Ko Crevostet, Forsythiae Fructus, Pogostemon cablin, Magnolia Officinalis. Compared with the LPS-induced lung injury model group, the medium dose of the new prescription group had significantly alleviated pathological changes in lung tissue, decreased lung coefficient, decreased contents of IL-6, TNF-a and IL-1ß, and increased mRNA and protein expression of ACE2 and AXL (P < 0.05). Conclusion: Based on data mining, network pharmacology and molecular docking technology, the new prescription for non-critical COVID-19 established by this method has an anti-inflammatory effect on rats with acute lung injury induced by lipopolysaccharide and can provide a reference for clinicians to alleviate the symptoms related to non-critical COVID-19. [ FROM AUTHOR] Copyright of Traditional Medicine Research is the property of TMR Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

8.
Risk Management ; 25(2):12, 2023.
Article in English | ProQuest Central | ID: covidwho-2287835

ABSTRACT

Based on the daily stock closing price data of 14 A-share listed banks in China from January 2009 to June 2021, this paper makes a comparative analysis of the contagion effect of risks in the banking industry before and after the outbreak of COVID-19. Based on the transfer entropy method, this paper calculates the correlation network matrix of inter-bank risk contagion effect and empirically studies the contagion effect of risks in the banking industry before and after the outbreak by using social network analysis method, depicting the network structure of systemic risk contagion in Chinese banking industry. This study found that the risk of inter-bank system increased significantly after the outbreak and the key nodes of bank risk contagion have also changed before and after the outbreak;state-owned banks are less risky, joint-stock banks and local financial institutions are riskier, and the contagion effect of risks between banks is asymmetric.

9.
Environ Sci Pollut Res Int ; 2022 Nov 10.
Article in English | MEDLINE | ID: covidwho-2279366

ABSTRACT

The spread of communicable diseases, such as COVID-19, has a detrimental effect on our socio-economic structure. In a dynamic log-run world, socio-economic and environmental factors interact to spread communicable diseases. We investigated the long-term interdependence of communicable disease spread, economic prosperity, greenhouse gas emissions, and government health expenditures in India's densely populated economy using a variance error correction (VEC) approach. The VEC model was validated using stationarity, cointegration, autocorrelation, heteroscedasticity, and normality tests. Our impulse response and variance decomposition analyses revealed that economic prosperity (GNI) significantly impacts the spread of communicable diseases, greenhouse gas emissions, government health expenditures, and GNI. Current health expenditures can reduce the need for future increases, and the spread of communicable diseases is detrimental to economic growth. Developing economies should prioritize economic growth and health spending to combat pandemics. Simultaneously, the adverse effects of economic prosperity on environmental degradation should be mitigated through policy incentives.

10.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2556085.v1

ABSTRACT

Background: COVID-19 has become one of the biggest challenges globally, yet no specifically effective medication has been developed. Mesenchymal stem cells (MSCs) exhibit properties of immune regulation and regeneration, which may suppress the over-inflammatory response and promote recovery of lung damage caused by COVID-19 and offer the potential as a therapeutic option. Methods: At the very beginning of COVID-19 epidemic in 2020, we investigated the use of human umbilical cord-derived MSCs (hUC-MSCs) as a salvage therapy in five severe COVID-19 patients, with each patient receiving intravenous infusion of hUC-MSCs three times. Results: All patients showed significant improvement in clinical manifestations, including laboratory biomarkers and findings of lung computed tomography images, after at least one dose of MSC therapy. Conclusion: These results suggest that MSC therapy is safe and can reduce the inflammatory response and alleviate the clinical symptoms of critically ill COVID-19 patients.


Subject(s)
COVID-19 , Lung Diseases
11.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2455872.v1

ABSTRACT

Wearing masks has become a new normal in our daily lives because of the global outbreak of COVID-2019 (COVID-19). To compare the differences in the facial microbiota of healthy women before and after wearing masks and to further explore the probable effect of the habits of regularly wearing masks on the facial microbiome, we re-enrolled the same 19 healthy female participants in our previous study and detected the microbial composition of facial DNA samples using 16S rRNA gene amplicon sequencing. Both alpha and beta diversity, and the abundance and function of facial microflora of recruited healthy women changed remarkably before and after wearing masks. The destination with different air quality indices, which ever was the strongest factor on microbial composition before wearing masks, no longer contributed to both microbiota composition and pathway after wearing masks. Sufficient sleep protected skin from sensitivity and apoptosis, which might be related to Prevotella expression and the function of cytochrome c. Maskne was the common complication of wearing masks. Suitable mask-wearing habits should be recommended to avoid facial skin problems.


Subject(s)
COVID-19
12.
Drugs and Clinic ; 36(12):2473-2487, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-2145036

ABSTRACT

Objective: To explore the effective components, target and signal pathway of Xuanfei Baidu Prescription in treatment of coronavirus infection, and to explain its mechanism of action. Methods A network of Character, taste, and meridian of Xuanfei Baidu Prescription was constructed using Cytoscape. Effective components and related targets of Xuanfei Baidu Prescription were selected by using TCMSP database, SwissADME database, and Swiss Target Prediction database. Disease targets of SARS, MERS and COVID-19 were collected using GeneCards database and CTD database. Drug targets and disease targets were intersected, and Cytoscape software was used to construct the network diagram. Using String database, the network model of protein-protein interaction (PPI) was constructed for potential targets. Metascape database was used for GO and KEGG enrichment analysis of potential targets, and Cytoscape was used to construct the network diagram. Results The results showed that 10 ingredients in Xuanfeibaidu Prescription are associated with the Lung meridian. 167 active components and 242 potential targets were screened out. The core drugs were Glycyrrhiza uralensis Fisch.,Ephedrae Herba, Artemisia annua L, Verbena officinalis L., Polygonum cuspidatum Sieb. et Zucc.. The core components were quercetin, stigmasterol, kaempferol, luteolin, isorhamnetin. The core targets were AKT1, IL-6, TP53, VEGFA, TNF. The possible mechanism of action is related to several signaling pathways such as PI3K-Akt signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, and so on. Conclusion This study explored the potential common mechanism of Xuanfei Baidu Prescription on SARS, MERS and COVID-19, reflecting the multi-component, multi-target and multi-pathway characteristics of TCM.

13.
Operations Management Research ; 15(3-4):1115-1133, 2022.
Article in English | ProQuest Central | ID: covidwho-2129162

ABSTRACT

COVID-19 pandemic outbreak caused supply chain (SC) disruption and threatened human life across the world, which could be mitigated through innovative strategies. Based on this scenario, this study examines the impact of COVID-19 on green practices, SC crisis mitigation strategies, smart technologies, and sustainable supply chain performance in the Pakistani manufacturing industry. Data was collected from Pakistani firms and employed structural equation modeling for testing hypotheses. The empirical results found that the COVID-19 pandemic is statistically related to green practices, SC crisis mitigation strategies, and smart technologies, while it harms sustainable supply chain performance. Moreover, green practices, SC crisis mitigation strategies, and smart technologies positively contribute to sustainable supply chain performance. The results of this study also confirmed the mediating role of green practices, SC crisis mitigation strategies, and smart technologies and moderating role organizational commitment in the context of a developing economy’s manufacturing industry. This study enhances awareness and understanding and contributes to the existing literature on verifying the link between COVID-19 pandemic and green practices, SC crisis mitigation strategies, and smart technologies to increase sustainable supply chain performance during a pandemic disruption in the Pakistani context. This study supports the managers of supply chain and manufacturing firms in adopting green practices and smart technologies. Also, it helps in the formation and successful implementation of SC crisis mitigation strategies during the crisis.

14.
Phytomedicine : international journal of phytotherapy and phytopharmacology ; 2022.
Article in English | EuropePMC | ID: covidwho-2125358

ABSTRACT

Background The significant clinical efficacy of Xuanfei Baidu Decoction (XFBD) is proven in the treatment of patients with coronavirus disease 2019 (COVID-19) in China. However, the mechanisms of XFBD against acute lung injury (ALI) are still poorly understood. Methods In vivo, the mouse model of ALI was induced by IgG immune complexes (IgG-IC), and then XFBD (4g/kg, 8g/kg) were administered by gavage respectively. 24h after inducing ALI, the lungs were collected for histological and molecular analysis. In vitro, alveolar macrophages inflammation models induced by IgG-IC were performed and treated with different dosage of XFBD-Containing Serum to investigate the protective role and molecular mechanisms of XFBD. Results The results revealed that XFBD mitigated lung injury and significantly downregulated the production of pro-inflammatory mediators in lung tissues and macrophages upon IgG-IC stimulation. Notably, XFBD attenuated C3a and C5a generation, inhibited the expression of C3aR and C5aR and suppressed the activation of JAK2/STAT3/SOCS3 and NF-κB signaling pathway in lung tissues and macrophages induced by IgG-IC. Moreover, in vitro experiments, we verified that Colivelin TFA (CAF, STAT3 activator) and C5a treatment markedly elevated the IgG-IC-triggered inflammatory responses in macrophages and XFBD weakened the effects of CAF or C5a. Conclusion XFBD suppressed complement overactivation and ameliorated IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB Signaling Pathway. These data contribute to understanding the mechanisms of XFBD in COVID-19 treatment. Graphical Image, graphical Schematic representation of proposed mechanism underlying the protective effects of XFBD on the IgG-IC-induced ALI. XFBD suppressed complement overactivation and protected against IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB Signaling Pathway.

15.
Renewable Energy ; 2022.
Article in English | ScienceDirect | ID: covidwho-2122767

ABSTRACT

Understanding the interactions among climate change, carbon emission allowance trading, crude oil and renewable energy stock markets, especially the role of climate change in this system is of great significance for policy makers, energy producers/consumers and relevant investors. The present paper aims to quantify the time-varying connectedness effects among the four factors by using the TVP-VAR based extensions of both time- and frequency-domain connectedness index measurements proposed by Antonakakis et al. (2020) and Ellington and Barunik (2021) [8,48]. The empirical results suggest that, firstly, the average total connectedness among climate change, carbon emission allowance trading, crude oil and renewable energy stock markets is not so strong for the heterogenous fundamentals underlying them. Nevertheless, the time-varying total connectedness fluctuates fiercely through May 2005 to September 2021, varying from about 8% to 30% and rocket to very high levels during the global subprime mortgage crisis and the COVID-19 pandemic. Furthermore, the total connectedness mainly centers on the short-term frequency, i.e., 1–3 months. Secondly, climate change is generally the leading information contributor among the four factors, although not particularly strong, and its leading role also performs mainly on the short-term frequency (1–3 months). Thirdly, renewable energy stock market and crude oil market show tight interactions between them and they are the two major bridges of information exchanges across various time frequencies (horizons) in this system. Finally, we confirm the evidence that the primary net connectedness contributor and receiver switch frequently across different time frequencies, implying that it is extremely essential for policy makers, energy producers/consumers and investors to make time-horizon-specific regulatory, production/purchasing or investment decisions when facing the uncertain effects of climate change on the interactions among carbon emission allowance, crude oil and renewable energy stock markets.

17.
Health data science ; 2021, 2021.
Article in English | EuropePMC | ID: covidwho-2112028

ABSTRACT

Background New York City (NYC) experienced an initial surge and gradual decline in the number of SARS-CoV-2-confirmed cases in 2020. A change in the pattern of laboratory test results in COVID-19 patients over this time has not been reported or correlated with patient outcome. Methods We performed a retrospective study of routine laboratory and SARS-CoV-2 RT-PCR test results from 5,785 patients evaluated in a NYC hospital emergency department from March to June employing machine learning analysis. Results A COVID-19 high-risk laboratory test result profile (COVID19-HRP), consisting of 21 routine blood tests, was identified to characterize the SARS-CoV-2 patients. Approximately half of the SARS-CoV-2 positive patients had the distinct COVID19-HRP that separated them from SARS-CoV-2 negative patients. SARS-CoV-2 patients with the COVID19-HRP had higher SARS-CoV-2 viral loads, determined by cycle threshold values from the RT-PCR, and poorer clinical outcome compared to other positive patients without the COVID12-HRP. Furthermore, the percentage of SARS-CoV-2 patients with the COVID19-HRP has significantly decreased from March/April to May/June. Notably, viral load in the SARS-CoV-2 patients declined, and their laboratory profile became less distinguishable from SARS-CoV-2 negative patients in the later phase. Conclusions Our longitudinal analysis illustrates the temporal change of laboratory test result profile in SARS-CoV-2 patients and the COVID-19 evolvement in a US epicenter. This analysis could become an important tool in COVID-19 population disease severity tracking and prediction. In addition, this analysis may play an important role in prioritizing high-risk patients, assisting in patient triaging and optimizing the usage of resources.

18.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2320746.v1

ABSTRACT

Background: Previous studies have shown that prone position may be beneficial for the treatment of acute respiratory distress syndrome (ARDS) or acute hypoxic respiratory failure (AHRF) in COVID-19 patients, but the results are not consistent, especially in terms of oxygenation outcomes and intubation rate. This systematic review and meta-analysis assessed the effects of prone position on AHRF in COVID-19 patients with all randomized controlled trials (RCTs). Methods: An extensive search of online databases, including MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials from December 1, 2019 to October 30, 2022, with no language restrictions. This systematic review and meta-analysis are based on the PRISMA statement and has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) with the registered ID: CRD42022367885. We only included RCTs and used Cochrane risk assessment tool for quality assessment. Results: Twelve RCTs fulfilled the selection criteria and 3154 patients were included. Meta-analysis found that patients in prone position group had more significant improvement in the SpO2/FiO2 ratio (mean difference [MD]: 29.76; 95% confidence interval [CI]: 1.39 to 48.13; P=0.001) compared with usual care. Prone position also reduced the need for intubation (odd ratio [OR]: 0.72; 95% CI: 0.62 to 0.85; P<0.0001; I2=0%). There was no significant difference in mortality, hospital length of stay, incidence of intensive care unit (ICU) admission and adverse events between the two groups. Conclusions: Prone position was a promising intervention method, which is beneficial to improve the oxygenation of patients with ARDS or AHRF caused by COVID-19 and can reduce the need for intubation. However, prone position had no significant difference in mortality, hospital length of stay, incidence of ICU admission and adverse events.


Subject(s)
COVID-19 , Respiratory Insufficiency , Respiratory Distress Syndrome
19.
Daniela Matuozzo; Estelle Talouarn; Astrid Marchal; Jeremy Manry; Yoann Seeleuthner; Yu Zhang; Alexandre Bolze; Matthieu Chaldebas; Baptiste Milisavljevic; Peng Zhang; Adrian Gervais; Paul Bastard; Takaki Asano; Lucy Bizien; Federica Barzaghi; Hassan Abolhassani; Ahmad Abou Tayoun; Alessandro Aiuti; Ilad Alavi Darazam; Luis Allende; Rebeca Alonso-Arias; Andres Augusto Arias; Gokhan Aytekin; Peter Bergman; Simone Bondesan; Yenan Bryceson; Ingrid Bustos; Oscar Cabrera-Marante; Sheila Carcel; Paola Carrera; Giorgio Casari; Khalil Chaibi; Roger Colobran; Antonio Condino-Neto; Laura Covill; Loubna El Zein; Carlos Flores; Peter Gregersen; Marta Gut; Filomeen Haerynck; Rabih Halwani; Selda Hancerli; Lennart Hammarstrom; Nevin Hatipoglu; Adem Karbuz; Sevgi Keles; Christele Kyheng; Rafael Leon-Lopez; Jose Luis Franco; Davood Mansouri; Javier Martinez-Picado; Ozge Metin Akcan; Isabelle Migeotte; Pierre-Emmanuel Morange; Guillaume Morelle; Andrea Martin-Nalda; Giuseppe Novelli; Antonio Novelli; Tayfun Ozcelik; Figen Palabiyik; Qiang Pan-Hammarstrom; Rebeca Perez de Diego; Laura Planas-Serra; Daniel Pleguezuelo; Carolina Prando; Aurora Pujol; Luis Felipe Reyes; Jacques Riviere; Carlos Rodriguez-Gallego; Julian Rojas; Patrizia Rovere-Querini; Agatha Schluter; Mohammad Shahrooei; Ali Sobh; Pere Soler-Palacin; Yacine Tandjaoui-Lambiotte; Imran Tipu; Cristina Tresoldi; Jesus Troya; Diederik van de Beek; Mayana Zatz; Pawel Zawadzki; Saleh Zaid Al-Muhsen; Hagit Baris-Feldman; Manish Butte; Stefan Constantinescu; Megan Cooper; Clifton Dalgard; Jacques Fellay; James Heath; Yu-Lung Lau; Richard Lifton; Tom Maniatis; Trine Mogensen; Horst von Bernuth; Alban Lermine; Michel Vidaud; Anne Boland; Jean-Francois Deleuze; Robert Nussbaum; Amanda Kahn-Kirby; France Mentre; Sarah Tubiana; Guy Gorochov; Florence Tubach; Pierre Hausfater; Isabelle Meyts; Shen-Ying Zhang; Anne Puel; Luigi Notarangelo; Stephanie Boisson-Dupuis; Helen Su; Bertrand Boisson; Emmanuelle Jouanguy; Jean-Laurent Casanova; Qian Zhang; Laurent Abel; Aurelie Cobat.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.22.22281221

ABSTRACT

Background We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and autoantibodies against type I IFN in another 15-20% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI:1.5-528.7, P=1.1x10-4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P=2.1x10-4). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P=3.4x10-3). When these 14 loci and TLR7 were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P=4.7x10-7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P=0.02). Finally, the patients 13 with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10-5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie lifethreatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.


Subject(s)
Metabolism, Inborn Errors , Pneumonia , Severe Acute Respiratory Syndrome , COVID-19
20.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2118946.v1

ABSTRACT

Background Passive immunotherapies to augment the humoral immunity against virus have been associated with prevention of severe illnesses and reduction of mortality of patients with coronavirus disease 2019 (COVID-19). However, less is known about the comparative effectiveness of different types of passive immunotherapies. The aim of this study is to compare efficacy and safety of passive immunotherapy in patients with COVID-19. Methods This is a two-part network meta-analysis which evaluate the efficacy of passive immunotherapy in outpatients and hospitalized patients separately. Electronic databases, including PubMed, EMBASE, and Cochrane CENTRAL were systematically searched for articles published before 26th April 2022. Randomized clinical trials that compared COVID-19 specific antiviral antibodies, convalescence plasma and hyperimmune anti-COVID-19 Intravenous Immunoglobulin with placebo, or control plasma, or standard of care in patients with COVID-19 were included. Two authors screened the studies independently. We extracted data and assessed the risk of bias of studies using the revised Cochrane risk of bias tool (RoB 2 tool) at study level. The primary outcome for outpatients is hospitalization within 30 days from randomization and are mortality, need of invasive mechanical ventilation, and severe advent events for hospitalized patients. Results In this systematic review and network meta-analysis, data were pooled from 41 eligible randomized control trials involving 42298 participants. In the first part of network meta-analysis which is consist of 9 eligible trials with 10093 participants, compared with control, specific antiviral antibodies (odds ratio [OR]: 0.22, 95% CI: 0.16, 0.28) rather than CP (OR: 0.75, 95%CI: 0.56, 1.01) reduced the risk of hospitalization; treatment with antibody reduced a greater risk of hospitalization (OR: 0.29, 95%CI: 0.19, 0.43) when compared with CP. For the analysis of secondary outcome in outpatients, antibody (OR: 0.10, 95%CI: 0.01, 0.37) rather than CP (OR: 0.81, 95%CI: 0.23, 2.78) reduced the risk of mortality. In the second party of meta-analysis, none of the passive immunotherapy was associated with the reduction of mortality, need of invasive mechanical ventilation and severe adverse events. Furthermore, none of passive immunotherapy was associated with improvement in 6 secondary outcomes. However, in subgroup analysis, the administration of antibody was associated with improvement of mortality, need of invasive mechanical ventilation, rate of discharge, duration of hospital stay, time to death and with less adverse events. Conclusions In this network meta-analysis of clinical trials of patients with COVID-19, we found that treatment with antiviral antibodies reduced the risk of hospitalization in outpatients. Among hospitalized adult patients, all three passive immunotherapies compared with control did not result in a statistically significant improvement of the primary outcomes, but use of neutralizing antibodies may lead to improvement of primary outcomes and key secondary outcomes in seronegative patients. Further development of broader-spectrum antibodies targeting to highly conserved domain of spike protein which avoids immune escape of new variants are needed.


Subject(s)
COVID-19
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