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1.
Pediatr Infect Dis J ; 41(12): e513-e516, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2190914

ABSTRACT

Although post-acute sequelae of COVID-19 among adult survivors has gained significant attention, data in children hospitalized for severe acute respiratory syndrome coronavirus 2 is limited. This study of commercially insured US children shows that those hospitalized with COVID-19 or multisystem inflammatory syndrome in children have a substantial burden of severe acute respiratory syndrome coronavirus 2 sequelae and associated health care visits postdischarge.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Adult , Humans , Aftercare , Follow-Up Studies , Patient Discharge , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/therapy , Disease Progression , Delivery of Health Care
2.
Journal of Personalized Medicine ; 13(1):25, 2023.
Article in English | MDPI | ID: covidwho-2166665

ABSTRACT

Previous research has demonstrated that chronic diseases can occur due to musculoskeletal (MS) pain and poor sleep. It is also worth noting that the caffeine in coffee can reduce overall sleep duration, efficiency, and quality. Thus, the present study examines the effects of frequent coffee drinking (two cups per day) on individuals experiencing MS pain and a lack of sleep during the COVID-19 period. This observational and cross-sectional study recruited 1615 individuals who completed the self-reported (Nordic musculoskeletal) questionnaire. Long-term, frequent coffee drinking and a sleep duration of less than 6 h per day were significantly associated with neck and shoulder pain among healthy individuals. The mediation model demonstrated that the shorter sleep duration and drinking multiple cups of coffee per day had a two-way relationship that worsened such pain over the long term. Specifically, individuals who experienced such pain frequently drank multiple cups of coffee per day, which, in turn, shortened their sleep durations. In summary, long-term coffee drinking creates a vicious cycle between MS pain and sleep duration. Therefore, the amount of coffee should be fewer than two cups per day for individuals who sleep less than 6 h per day or suffer from MS pain, especially neck and shoulder pain.

3.
Glob Health Res Policy ; 7(1): 45, 2022 Nov 28.
Article in English | MEDLINE | ID: covidwho-2139788

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has posed particular health risks to United Nations peacekeepers, which require prompt responses and global attention. Since the health protection of United Nations peacekeepers against the COVID-19 pandemic is a typical global health problem, strategies from global health perspectives may help address it. From global health perspectives, and referring to the successful health protection of the Chinese Anti-Ebola medical team in Liberia, a conceptual framework was developed for the health protection of United Nations peacekeepers against the COVID-19 pandemic. Within this framework, the features include multiple cross-borders (cross-border risk factors, impact, and actions); multiple risk factors (Social Determinants of Health), multiple disciplines (public health, medicine, politics, diplomacy, and others), and extensive interdepartmental cooperation. These strategies include multiple phases (before-deployment, during-deployment, and post-deployment), multi-level cooperation networks (the United Nations, host countries, troop-contributing countries, the United Nations peacekeeping team, and United Nations peacekeepers), and concerted efforts from various dimensions (medical, psychological, and social).


Subject(s)
COVID-19 , Pandemics , Humans , Pandemics/prevention & control , COVID-19/epidemiology , COVID-19/prevention & control , Global Health , Public Health , United Nations
4.
International Journal of Molecular Sciences ; 23(23):14796, 2022.
Article in English | MDPI | ID: covidwho-2123707

ABSTRACT

To explore the mechanistic origin that determines the binding affinity of SARS-CoV-2 spike receptor binding domain (RBD) to human angiotensin converting enzyme 2 (ACE2), we constructed the homology models of RBD-ACE2 complexes of four Omicron subvariants (BA.1, BA.2, BA.3 and BA.4/5), and compared them with wild type complex (RBDWT-ACE2) in terms of various structural dynamic properties by molecular dynamics (MD) simulations and binding free energy (BFE) calculations. The results of MD simulations suggest that the RBDs of all the Omicron subvariants (RBDOMIs) feature increased global structural fluctuations when compared with RBDWT. Detailed comparison of BFE components reveals that the enhanced electrostatic attractive interactions are the main determinant of the higher ACE2-binding affinity of RBDOMIs than RBDWT, while the weakened electrostatic attractive interactions determine RBD of BA.4/5 subvariant (RBDBA.4/5) lowest ACE2-binding affinity among all Omicron subvariants. The per-residue BFE decompositions and the hydrogen bond (HB) networks analyses indicate that the enhanced electrostatic attractive interactions are mainly through gain/loss of the positively/negatively charged residues, and the formation or destruction of the interfacial HBs and salt bridges can also largely affect the ACE2-binding affinity of RBD. It is worth pointing out that since Q493R plays the most important positive contribution in enhancing binding affinity, the absence of this mutation in RBDBA.4/5 results in a significantly weaker binding affinity to ACE2 than other Omicron subvariants. Our results provide insight into the role of electrostatic interactions in determining of the binding affinity of SARS-CoV-2 RBD to human ACE2.

5.
International Journal of Environmental Research and Public Health ; 19(23):15811, 2022.
Article in English | MDPI | ID: covidwho-2123684

ABSTRACT

Since the onset of the COVID-19 pandemic, burnout symptoms have been prevalent among healthcare workers. Living with spouses can be complex and was associated with an increased burnout risk during the COVID-19 pandemic. This study investigated the relationship between living with spouses and burnout among healthcare workers during the COVID-19 pandemic. We distributed questionnaires to participants working in a hospital affiliated with a medical university in Taiwan. The questionnaires were the Copenhagen Burnout Inventory, which comprises personal burnout (PB), work-related burnout (WB), and client burnout subscales;the Nordic Musculoskeletal Questionnaire;and information on basic demographic variables, family factors, living habits, work-related factors, and physical health factors. Multiple linear regression and mediation analysis were used. We obtained 1615 (63.81%) valid questionnaires. After analysis revealed that marriage was an independent risk factor for PB;however, the effect of marriage on WB was nonsignificant after controlling for risk factors. Parenthood, less alcohol use, reported sleep duration less than six hours, less overtime, less shift work, and participation in leisure activities with family and friends were found to be mediators between marriage and a lower WB level. In addition, chronic diseases, frequent neck pain, and shoulder pain were suppression factors. In summary, marriage was associated with an increased risk of PB. Married individuals sustain a high WB level because of changes in family roles, living conditions, and work conditions. Overall, helping healthcare workers to maintain well-being in marriage or family living may be effective in decreasing burnout during the COVID-19 pandemic.

6.
Diagnostic Microbiology and Infectious Disease ; : 115860, 2022.
Article in English | ScienceDirect | ID: covidwho-2104789

ABSTRACT

Diagnostic accuracy of COVID-19 varies among different assays. In this study, the analytical performance of one rapid nucleic acid detection assay (Coyote assay) and two routine RT-qPCR assays (BioGerm assay and DaAn assay) was evaluated, using 1196 clinical samples. Disagreement in the results of two paired targets occurred in all three assays. The Coyote assay failed to detect 15 samples, and the DaAn assay failed to detect 5 samples. The Cohen's kappa coefficient was 0.970 between the BioGerm and DaAn assays, 0.907 between the Coyote and BioGerm assays, and 0.936 between the Coyote and DaAn assays. The positive percent agreement (PPA), and negative percent agreement (NPA) of the Coyote assay were 84.04%, and 100%, respectively. Our study revealed that the results of the Coyote, BioGerm, and DaAn assays were highly consistent, which provided reference for the application of these assays for diagnosis of COVID-19.

7.
Environ Microbiol ; 23(12): 7373-7381, 2021 12.
Article in English | MEDLINE | ID: covidwho-2078263

ABSTRACT

Coronavirus disease 2019 (COVID-19) pandemic has caused high number of infections and deaths of healthcare workers globally. Distribution and possible transmission route of SARS-CoV-2 in hospital environment should be clarified. We herein collected 431 environmental (391 surface and 40 air) samples in the intensive care unit (ICU) and general wards (GWs) of three hospitals in Wuhan, China from February 21 to March 4, 2020, and detected SARS-CoV-2 RNA by real-time quantitative PCR. The viral positive rate in the contaminated areas was 17.8% (28/157), whereas there was no virus detected in the clean areas. Higher positive rate (22/59, 37.3%) was found in ICU than that in GWs (3/63, 4.8%). The surfaces of computer keyboards and mouse in the ICU were the most contaminated (8/10, 80.0%), followed by the ground (6/9, 66.7%) and outer glove (2/5, 40.0%). From 17 air samples in the contaminated areas, only one sample collected at a distance of around 30 cm from the patient was positive. Enhanced surface disinfection and hand hygiene effectively decontaminated the virus from the environment. This finding might help understand the transmission route and contamination risk of SARS-CoV-2 and evaluate the effectiveness of infection prevention and control measures in healthcare facilities.


Subject(s)
COVID-19 , Hospitals , Humans , Pandemics , RNA, Viral/genetics , SARS-CoV-2
8.
JAMA Pediatr ; 176(10): 1000-1009, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-1999806

ABSTRACT

Importance: The postacute sequelae of SARS-CoV-2 infection (PASC) has emerged as a long-term complication in adults, but current understanding of the clinical presentation of PASC in children is limited. Objective: To identify diagnosed symptoms, diagnosed health conditions, and medications associated with PASC in children. Design, Setting and Participants: This retrospective cohort study used electronic health records from 9 US children's hospitals for individuals younger than 21 years who underwent antigen or reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 between March 1, 2020, and October 31, 2021, and had at least 1 encounter in the 3 years before testing. Exposures: SARS-CoV-2 positivity by viral test (antigen or RT-PCR). Main Outcomes and Measures: Syndromic (symptoms), systemic (conditions), and medication PASC features were identified in the 28 to 179 days following the initial test date. Adjusted hazard ratios (aHRs) were obtained for 151 clinically predicted PASC features by contrasting viral test-positive groups with viral test-negative groups using proportional hazards models, adjusting for site, age, sex, testing location, race and ethnicity, and time period of cohort entrance. The incidence proportion for any syndromic, systemic, or medication PASC feature was estimated in the 2 groups to obtain a burden of PASC estimate. Results: Among 659 286 children in the study sample, 348 091 (52.8%) were male, and the mean (SD) age was 8.1 (5.7) years. A total of 59 893 (9.1%) tested positive by viral test for SARS-CoV-2, and 599 393 (90.9%) tested negative. Most were tested in outpatient testing facility settings (322 813 [50.3%]) or office settings (162 138 [24.6%]). The most common syndromic, systemic, and medication features were loss of taste or smell (aHR, 1.96; 95% CI, 1.16-3.32), myocarditis (aHR, 3.10; 95% CI, 1.94-4.96), and cough and cold preparations (aHR, 1.52; 95% CI, 1.18-1.96), respectively. The incidence of at least 1 systemic, syndromic, or medication feature of PASC was 41.9% (95% CI, 41.4-42.4) among viral test-positive children vs 38.2% (95% CI, 38.1-38.4) among viral test-negative children, with an incidence proportion difference of 3.7% (95% CI, 3.2-4.2). A higher strength of association for PASC was identified in those cared for in the intensive care unit during the acute illness phase, children younger than 5 years, and individuals with complex chronic conditions. Conclusions and Relevance: In this large-scale, exploratory study, the burden of pediatric PASC that presented to health systems was low. Myocarditis was the most commonly diagnosed PASC-associated condition. Acute illness severity, young age, and comorbid complex chronic disease increased the risk of PASC.


Subject(s)
COVID-19 , Myocarditis , Adolescent , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Child , Female , Humans , Male , Retrospective Studies , SARS-CoV-2 , Young Adult
9.
Hum Vaccin Immunother ; : 2102329, 2022 Aug 17.
Article in English | MEDLINE | ID: covidwho-1984960

ABSTRACT

Patients with cancer are considered at high risk of COVID-19 related complications with higher mortality rates than healthy individuals. This study investigated the perception, acceptance, and influencing factors of COVID-19 vaccination among cancer patients in Guangzhou, China. A cross-sectional survey was conducted in Guangzhou, China from August to November 2021 in two tertiary medical centers. Outpatients were recruited through hospital posters to complete a questionnaire including demographics, medical history, knowledge, and attitude toward COVID-19 vaccines and COVID-19 vaccination status. Chi-square tests and multivariable logistic regression were used to analyze predictors for acceptance of COVID-19 vaccination. In total, only 75 out of 343 patients (21.87%) had received at least one dose of COVID-19 vaccine. Twenty-one patients (6.12%) had received a recommendation about COVID-19 vaccination from their physicians. Patients who were recommended by physicians to get vaccinated (aOR = 11.71 95% CI: 2.71-50.66), with a monthly income of more than CNY 5000 (aOR = 3.94, 95% CI: 1.88-8.26) were more likely to have received COVID-19 vaccination. Cancer patients who had been diagnosed for more than one year (aOR = 0.21, 95% CI: 0.09-0.51), had received multiple cancer treatment strategies (aOR = 0.34, 95% CI: 0.16-0.74), worried about the safety of COVID-19 vaccines (aOR = 0.21, 95% CI: 0.11-0.40), were less likely to have received COVID-19 vaccination. COVID-19 vaccination uptake among cancer patients was insufficient. The proportion of cancer patients receiving vaccination recommendations from physicians remains inadequate. Physicians are expected to play an essential role in patients' knowledge of the safety and effectiveness of COVID-19 vaccines.

10.
J Med Virol ; 94(11): 5284-5293, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1935699

ABSTRACT

Little is known about the characteristics of respiratory tract microbiome in Coronavirus disease 2019 (COVID-19) inpatients with different severity. We conducted a study that expected to clarify these characteristics as much as possible. A cross-sectional study was conducted to characterize respiratory tract microbial communities of 69 COVID-19 inpatients from 64 nasopharyngeal swabs and 5 sputum specimens using 16S ribosomal RNA gene V3-V4 region sequencing. The bacterial profiles were analyzed to find potential biomarkers by the two-step method, the combination of random forest model and the linear discriminant analysis effect size, and explore the connections with clinical characteristics by Spearman's rank test. Compared with mild COVID-19 patients, severe patients had significantly decreased bacterial diversity (p-values were less than 0.05 in the alpha and beta diversity) and relative lower abundance of opportunistic pathogens, including Actinomyces, Prevotella, Rothia, Streptococcus, Veillonella. Eight potential biomarkers including Treponema, Leptotrichia, Lachnoanaerobaculum, Parvimonas, Alloprevotella, Porphyromonas, Gemella, and Streptococcus were found to distinguish the mild COVID-19 patients from the severe COVID-19 patients. The genera of Actinomyces and Prevotella were negatively correlated with age in two groups. Intensive care unit admission, neutrophil count, and lymphocyte count were significantly correlated with different genera in the two groups. In addition, there was a positive correlation between Klebsiella and white blood cell count in two groups. The respiratory tract microbiome had significant differences in COVID-19 patients with different severity. The value of the respiratory tract microbiome as predictive biomarkers for COVID-19 severity deserves further exploration.


Subject(s)
COVID-19 , Microbiota , Bacteria/genetics , COVID-19/diagnosis , Cross-Sectional Studies , Humans , Microbiota/genetics , Respiratory System , Severity of Illness Index
11.
Infect Drug Resist ; 15: 3683-3691, 2022.
Article in English | MEDLINE | ID: covidwho-1938525

ABSTRACT

Aim: One of the most common laboratory findings in COVID-19 patients has been observed to be hypercoagulability with elevated D-dimer levels. An activation of thrombosis may be generated by hyperglycemia. We aimed to explore the association between D-dimer and in-hospital outcomes, and evaluate the synergistic effect between elevated D-dimer and hyperglycemia on COVID-19 prognosis. Methods: A retrospective cohort study was undertaken with 2467 COVID-19 inpatients. D-dimer and fasting blood glucose (FBG) on admission and adverse in-hospital outcomes (events of death and aggravated severity) were collected. Cox proportional risk model was performed to assess the association of D-dimer and adverse in-hospital outcomes, and the combined effects of D-dimer and FBG. Results: Among these COVID-19 patients, 1100 (44.6%) patients had high D-dimer (≥0.50 mg/L). Patients with high D-dimer were older, with higher FBG (≥7.00 mmol/L), and had significantly higher adjusted risk of adverse in-hospital outcomes when comparing with those who with D-dimer<0.50 mg/L (hazard ratio, 2.73; 95% confidence interval, 1.46-5.11). Moreover, patients with high FBG and D-dimer levels had an increasing risk (hazard ratio, 5.72; 95% confidence interval: 2.65-12.34) than those with normal FBG and D-dimer. Conclusion: Risk of adverse in-hospital outcomes is higher among patients with high D-dimer levels. Additionally, this study found for the first time that elevated D-dimer and hyperglycemia had a synergistic effect on COVID-19 prognosis, and this risk was independent of diabetes history.

12.
Front Immunol ; 13: 888612, 2022.
Article in English | MEDLINE | ID: covidwho-1928420

ABSTRACT

HAPLN1 maintains aggregation and the binding activity of extracellular matrix (ECM) molecules (such as hyaluronic acid and proteoglycan) to stabilize the macromolecular structure of the ECM. An increase in HAPLN1 expression is observed in a few types of musculoskeletal diseases including rheumatoid arthritis (RA); however, its functions are obscure. This study examined the role of HAPLN1 in determining the viability, proliferation, mobility, and pro-inflammatory phenotype of RA- fibroblast-like synoviocytes (RA-FLSs) by using small interfering RNA (siHAPLN1), over-expression vector (HAPLN1OE), and a recombinant HAPLN1 (rHAPLN1) protein. HAPLN1 was found to promote proliferation but inhibit RA-FLS migration. Metformin, an AMPK activator, was previously found by us to be able to inhibit FLS activation but promote HAPLN1 secretion. In this study, we confirmed the up-regulation of HAPLN1 in RA patients, and found the positive relationship between HAPLN1 expression and the AMPK level. Treatment with either si-HAPLN1 or HAPLN1OE down-regulated the expression of AMPK-ɑ gene, although up-regulation of the level of p-AMPK-ɑ was observed in RA-FLSs. si-HAPLN1 down-regulated the expression of proinflammatory factors like TNF-ɑ, MMPs, and IL-6, while HAPLN1OE up-regulated their levels. qPCR assay indicated that the levels of TGF-ß, ACAN, fibronectin, collagen II, and Ki-67 were down-regulated upon si-HAPLN1 treatment, while HAPLN1OE treatment led to up-regulation of ACAN and Ki-67 and down-regulation of cyclin-D1. Proteomics of si-HAPLN1, rHAPLN1, and mRNA-Seq analysis of rHAPLN1 confirmed the functions of HAPLN1 in the activation of inflammation, proliferation, cell adhesion, and strengthening of ECM functions. Our results for the first time demonstrate the function of HAPLN1 in promoting the proliferation and pro-inflammatory phenotype of RA-FLSs, thereby contributing to RA pathogenesis. Future in-depth studies are required for better understanding the role of HAPLN1 in RA.


Subject(s)
Arthritis, Rheumatoid , Synoviocytes , AMP-Activated Protein Kinases/metabolism , Arthritis, Rheumatoid/metabolism , Cell Proliferation , Cell Survival/genetics , Extracellular Matrix Proteins , Fibroblasts/metabolism , Humans , Ki-67 Antigen/metabolism , Phenotype , Proteoglycans , Synoviocytes/metabolism
13.
Sci Rep ; 12(1): 11073, 2022 06 30.
Article in English | MEDLINE | ID: covidwho-1921704

ABSTRACT

Integrating data across institutions can improve learning efficiency. To integrate data efficiently while protecting privacy, we propose A one-shot, summary-statistics-based, Distributed Algorithm for fitting Penalized (ADAP) regression models across multiple datasets. ADAP utilizes patient-level data from a lead site and incorporates the first-order (ADAP1) and second-order gradients (ADAP2) of the objective function from collaborating sites to construct a surrogate objective function at the lead site, where model fitting is then completed with proper regularizations applied. We evaluate the performance of the proposed method using both simulation and a real-world application to study risk factors for opioid use disorder (OUD) using 15,000 patient data from the OneFlorida Clinical Research Consortium. Our results show that ADAP performs nearly the same as the pooled estimator but achieves higher estimation accuracy and better variable selection than the local and average estimators. Moreover, ADAP2 successfully handles heterogeneity in covariate distributions.


Subject(s)
Algorithms , Opioid-Related Disorders , Computer Simulation , Datasets as Topic , Humans , Opioid-Related Disorders/epidemiology , Regression Analysis , Risk Factors
14.
Anal Chem ; 94(27): 9603-9609, 2022 07 12.
Article in English | MEDLINE | ID: covidwho-1921541

ABSTRACT

The clustered regularly interspaced short palindromic repeats (CRISPR)-based nucleic acid detection can be combined with recombinase-aided amplification (RAA) to enable rapid, accurate, and early detection of SARS-CoV-2. Current CRISPR-based approaches to detecting viral nucleic acid typically require immense manual operations to transfer RPA amplicons for CRISPR detection or suffer from compromised sensitivity by mixing the competing RPA amplification and CRISPR detection. Here, we develop dual-CRISPR/Cas12a-assisted RT-RAA assay and a ″sample-to-answer″ centrifugal microfluidic platform that can automatically detect 1 copy/µL of the SARS-CoV-2 within 30 min. This chip separates the amplification (RAA) from detection (CRISPR), such that sensitivity is maximized and the time consumption is decreased by a factor of 3. For the 26 positive and 8 negative clinical SARS-CoV-2 samples, this automated centrifugal microfluidics achieved 100% accuracy compared to the gold-standard RT-PCR technique. This point-of-care test, with the advantages of being one-step, automated, rapid, and sensitive, will have a significant potential for clinical diagnosis and disease prevention.


Subject(s)
COVID-19 , Nucleic Acids , COVID-19/diagnosis , CRISPR-Cas Systems , Humans , Microfluidics , Nucleic Acid Amplification Techniques/methods , Recombinases , SARS-CoV-2/genetics , Sensitivity and Specificity
15.
Sci Rep ; 12(1): 10946, 2022 06 29.
Article in English | MEDLINE | ID: covidwho-1908278

ABSTRACT

Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines ("Pfizer" vaccine dose 1 and 2, "Moderna" vaccine dose 1 and 2, and "Janssen" vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports between December 14, 2020 and September 17, 2021. AE rankings of the five vaccine groups calculated separately by RCT and VAERS were consistent, especially for systemic AEs. For severe AEs reported in VAERS, the reported risks of thrombosis and GBS after Janssen vaccine were highest. The reported risk of shingles after the first dose of Moderna vaccine was highest, followed by the second dose of the Moderna vaccine. The reported risk of myocarditis was higher after the second dose of Pfizer and Moderna vaccines. The reported risk of anaphylaxis was higher after the first dose of Pfizer vaccine. Limitations of this study are the inherent biases of the spontaneous reporting system data, and only including three pivotal RCTs and no comparison with other active vaccine safety surveillance systems.


Subject(s)
COVID-19 Vaccines , Vaccination , Adverse Drug Reaction Reporting Systems , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Randomized Controlled Trials as Topic , United States/epidemiology , Vaccination/adverse effects
16.
Frontiers in molecular biosciences ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1905153

ABSTRACT

There are still frequent reports that a number of recovered coronavirus disease 2019 (COVID-19) patients following discharge have re-detectable positive (RP) results by RT-PCR. Understanding the clinical and molecular characteristics of RP patients may have implications for curbing the COVID-19 pandemic. In this study, 318 COVID-19 convalescent patients, including 59 RP patients and 259 non-RP (NRP) patients, were enrolled. Among RP patients, women accounted for a significantly high proportion (67.8%), and the titers of IgG and IgM antibodies in this group were also significantly high. Differentially expressed genes (DEGs), including 692 upregulated and 383 downregulated genes, overlapped in two public GEO datasets containing RP and NRP blood cell samples. Enrichment analysis indicated that these DEGs were related to several key signaling pathways, such as viral infection, immune activation, and inflammatory responses. Importantly, 59 indicator genes constituting the core network exhibited high diagnostic values and were correlated with markers of different immune cells. Among these, 12 drug-related genes were associated with the RP results. Our work suggests that, in addition to clinically available features, blood cell transcriptome sequencing can be performed to obtain gene signatures for diagnosis of RP patients.

17.
NPJ Digit Med ; 5(1): 76, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1890278

ABSTRACT

Integrating real-world data (RWD) from several clinical sites offers great opportunities to improve estimation with a more general population compared to analyses based on a single clinical site. However, sharing patient-level data across sites is practically challenging due to concerns about maintaining patient privacy. We develop a distributed algorithm to integrate heterogeneous RWD from multiple clinical sites without sharing patient-level data. The proposed distributed conditional logistic regression (dCLR) algorithm can effectively account for between-site heterogeneity and requires only one round of communication. Our simulation study and data application with the data of 14,215 COVID-19 patients from 230 clinical sites in the UnitedHealth Group Clinical Research Database demonstrate that the proposed distributed algorithm provides an estimator that is robust to heterogeneity in event rates when efficiently integrating data from multiple clinical sites. Our algorithm is therefore a practical alternative to both meta-analysis and existing distributed algorithms for modeling heterogeneous multi-site binary outcomes.

18.
Elife ; 112022 06 07.
Article in English | MEDLINE | ID: covidwho-1879632

ABSTRACT

TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using trophoblasts as a model for cell fusion, we demonstrate that Ca2+ influx through the Ca2+ permeable transient receptor potential vanilloid channel TRPV4 is critical for TMEM16F activation and plays a role in subsequent human trophoblast fusion. GSK1016790A, a TRPV4 specific agonist, robustly activates TMEM16F in trophoblasts. We also show that TRPV4 and TMEM16F are functionally coupled within Ca2+ microdomains in a human trophoblast cell line using patch-clamp electrophysiology. Pharmacological inhibition or gene silencing of TRPV4 hinders TMEM16F activation and subsequent trophoblast syncytialization. Our study uncovers the functional expression of TRPV4 and one of the physiological activation mechanisms of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically and disease-relevant cell fusion events.


Subject(s)
Anoctamins/metabolism , COVID-19 , HIV Infections , Phospholipid Transfer Proteins/metabolism , Calcium/metabolism , Female , Humans , Placenta/metabolism , Pregnancy , RNA, Viral , SARS-CoV-2 , TRPV Cation Channels/genetics , TRPV Cation Channels/metabolism , Trophoblasts/metabolism
19.
J Biomed Inform ; 131: 104097, 2022 07.
Article in English | MEDLINE | ID: covidwho-1867315

ABSTRACT

BACKGROUND: Observational studies incorporating real-world data from multiple institutions facilitate study of rare outcomes or exposures and improve generalizability of results. Due to privacy concerns surrounding patient-level data sharing across institutions, methods for performing regression analyses distributively are desirable. Meta-analysis of institution-specific estimates is commonly used, but has been shown to produce biased estimates in certain settings. While distributed regression methods are increasingly available, methods for analyzing count outcomes are currently limited. Count data in practice are commonly subject to overdispersion, exhibiting greater variability than expected under a given statistical model. OBJECTIVE: We propose a novel computational method, a one-shot distributed algorithm for quasi-Poisson regression (ODAP), to distributively model count outcomes while accounting for overdispersion. METHODS: ODAP incorporates a surrogate likelihood approach to perform distributed quasi-Poisson regression without requiring patient-level data sharing, only requiring sharing of aggregate data from each participating institution. ODAP requires at most three rounds of non-iterative communication among institutions to generate coefficient estimates and corresponding standard errors. In simulations, we evaluate ODAP under several data scenarios possible in multi-site analyses, comparing ODAP and meta-analysis estimates in terms of error relative to pooled regression estimates, considered the gold standard. In a proof-of-concept real-world data analysis, we similarly compare ODAP and meta-analysis in terms of relative error to pooled estimatation using data from the OneFlorida Clinical Research Consortium, modeling length of stay in COVID-19 patients as a function of various patient characteristics. In a second proof-of-concept analysis, using the same outcome and covariates, we incorporate data from the UnitedHealth Group Clinical Discovery Database together with the OneFlorida data in a distributed analysis to compare estimates produced by ODAP and meta-analysis. RESULTS: In simulations, ODAP exhibited negligible error relative to pooled regression estimates across all settings explored. Meta-analysis estimates, while largely unbiased, were increasingly variable as heterogeneity in the outcome increased across institutions. When baseline expected count was 0.2, relative error for meta-analysis was above 5% in 25% of iterations (250/1000), while the largest relative error for ODAP in any iteration was 3.59%. In our proof-of-concept analysis using only OneFlorida data, ODAP estimates were closer to pooled regression estimates than those produced by meta-analysis for all 15 covariates. In our distributed analysis incorporating data from both OneFlorida and the UnitedHealth Group Clinical Discovery Database, ODAP and meta-analysis estimates were largely similar, while some differences in estimates (as large as 13.8%) could be indicative of bias in meta-analytic estimates. CONCLUSIONS: ODAP performs privacy-preserving, communication-efficient distributed quasi-Poisson regression to analyze count outcomes using data stored within multiple institutions. Our method produces estimates nearly matching pooled regression estimates and sometimes more accurate than meta-analysis estimates, most notably in settings with relatively low counts and high outcome heterogeneity across institutions.


Subject(s)
COVID-19 , Algorithms , COVID-19/epidemiology , Humans , Likelihood Functions , Models, Statistical , Regression Analysis
20.
Shanghai Journal of Preventive Medicine ; 33(1):25-32, 2021.
Article in Chinese | GIM | ID: covidwho-1865687

ABSTRACT

Objective: To determine the association between global epidemic of COVID-19 and local situation of imported cases from abroad to Shanghai, and then to predict the risk of imported COVID-19 epidemic from December 2020 through March 2021.

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