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1.
Anal Chem ; 94(18): 6703-6710, 2022 05 10.
Article in English | MEDLINE | ID: covidwho-1815468

ABSTRACT

Ratiometric assays of label-free dual-signaling reporters with enzyme-free amplification are intriguing yet challenging. Herein, yellow- and red-silver nanocluster (yH-AgNC and rH-AgNC) acting as bicolor ratiometric emitters are guided to site-specifically cluster in two template signaling hairpins (yH and rH), respectively, and originally, both of them are almost non-fluorescent. The predesigned complement tethered in yH is recognizable to a DNA trigger (TOC) related to SARS-CoV-2. With the help of an enhancer strand (G15E) tethering G-rich bases (G15) and a linker strand (LS), a switchable DNA construct is assembled via their complementary hybridizing with yH and rH, in which the harbored yH-AgNC close to G15 is lighted-up. Upon introducing TOC, its affinity ligating with yH is further implemented to unfold rH and induce the DNA construct switching into closed conformation, causing TOC-repeatable recycling amplification through competitive strand displacement. Consequently, the harbored rH-AgNC is also placed adjacent to G15 for turning on its red fluorescence, while the yH-AgNC is retainable. As demonstrated, the intensity ratio dependent on varying TOC is reliable with high sensitivity down to 0.27 pM. By lighting-up dual-cluster emitters using one G15 enhancer, it would be promising to exploit a simpler ratiometric biosensing format for bioassays or clinical theranostics.


Subject(s)
Biosensing Techniques , COVID-19 , Metal Nanoparticles , COVID-19/diagnosis , DNA , Fluorescence , Humans , SARS-CoV-2 , Silver , Spectrometry, Fluorescence
2.
Atmospheric Pollution Research ; : 101436, 2022.
Article in English | ScienceDirect | ID: covidwho-1803526

ABSTRACT

Continuous measurements of gaseous elemental mercury (GEM) were conducted in Qingdao from March 2020 to March 2021. The average concentration of GEM was (2.39 ± 1.07 ng/m3) with a variation range of 0.27–10.78 ng/m3. GEM exhibited a clear pattern of daily variation, with daily peaks occurring between 11:00–13:00. GEM concentrations were higher in winter (2.80 ± 1.28 ng/m3) than that in summer (2.18 ± 1.05 ng/m3). The high winter concentrations were related to coal-fired heating and the increased frequency of polluted weather in northern China. Principal component analysis showed that the main factors affecting GEM concentration were fossil fuel combustion, natural source release and atmospheric diffusion conditions. The anthropogenic emission sources were the main source of GEM in spring and winter, and natural sources of GEM was large in summer. The potential source contribution function suggested that North and Central China were the main potential sources of GEM, and there were large differences in the potential sources of GEM in different seasons. Comparing the GEM in the same time periods in 2018, 2020, and 2021, government policies, temporary lockdown measures for the COVID-19 epidemic, and urban village renovation led to a decreasing trend of GEM concentrations. This study contributes to a better understanding of the effects of long-range transport of air masses and anthropogenic emissions on atmospheric mercury in eastern coastal cities and offshore areas.

3.
Arthritis Care Res (Hoboken) ; 2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1750293

ABSTRACT

OBJECTIVE: COVID-19 patients with rheumatic disease have a higher risk of mechanical ventilation than the general population. We assessed lung involvement using a validated deep learning algorithm that extracts a quantitative measure of radiographic lung disease severity. METHODS: We performed a comparative cohort study of rheumatic disease patients with COVID-19 and ≥1chest radiograph within ±2 weeks of COVID-19 diagnosis and matched comparators. We used unadjusted and adjusted (for age, Charlson Comorbidity Index, and interstitial lung disease) quantile regression to compare the maximum Pulmonary X-Ray Severity (PXS) score at the 10th -90th percentiles between groups. We evaluated the association of severe PXS score (>9) with mechanical ventilation and death using Cox regression. RESULTS: We identified 70 patients with rheumatic disease and 463 general population comparators. Maximum PXS scores were similar in the rheumatic disease patients and comparators at the 10th -60th percentiles but significantly higher among rheumatic disease patients at the 70th -90th percentiles (90th percentile score of 10.2 vs. 9.2, adjusted p=0.03). Rheumatic disease patients were more likely to have a PXS score >9 (20% vs. 11%, p=0.02), indicating severe pulmonary disease. Rheumatic disease patients with PXS scores >9 vs. ≤9 had higher risk of mechanical ventilation (HR 24.1 [95% CI: 6.7, 86.9]) and death (HR 8.2 [95% CI: 0.7, 90.4]). CONCLUSIONS: Rheumatic disease patients with COVID-19 had more severe radiographic lung involvement than comparators. Higher PXS scores were associated with mechanical ventilation and will be important for future studies leveraging big data to assess COVID-19 outcomes in rheumatic disease patients. This article is protected by copyright. All rights reserved.

4.
Chin Med ; 17(1): 30, 2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1714659

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19), traditional Chinese medicine (TCM) has made an important contribution to the prevention and control of the epidemic. This review aimed to evaluate the efficacy and explore the mechanisms of TCM for COVID-19. We systematically searched 7 databases from their inception up to July 21, 2021, to distinguish randomized controlled trials (RCTs), cohort studies (CSs), and case-control studies (CCSs) of TCM for COVID-19. Two reviewers independently completed the screening of literature, extraction of data, and quality assessment of included studies. Meta-analysis was performed using Review Manager 5.4 software. Eventually, 29 RCTs involving 3060 patients and 28 retrospective studies (RSs) involving 12,460 patients were included. The meta-analysis demonstrated that TCM could decrease the proportion of patients progressing to severe cases by 55% and the mortality rate of severe or critical patients by 49%. Moreover, TCM could relieve clinical symptoms, curtail the length of hospital stay, improve laboratory indicators, and so on. In addition, we consulted the literature and obtained 149 components of Chinese medicinal herbs that could stably bind to antiviral targets or anti-inflammatory or immune-regulating targets by the prediction of molecular docking. It suggested that the mechanisms involved anti-virus, anti-inflammation, and regulation of immunity. Our study made a systematic review on the efficacy of TCM for COVID-19 and discussed the possible mechanisms, which provided clinical reference and theoretical basis for further research on the mechanism of TCM for COVID-19.

5.
Buildings ; 12(2):185, 2022.
Article in English | MDPI | ID: covidwho-1674509

ABSTRACT

The relationship between corporate social responsibility (CSR) and corporate financial performance (CFP) has been crucial in academia and business circles. Numerous construction firms have continued to internationalize construction business over time despite the influence of the COVID-19. The internationalization of construction business makes the CSR–CFP relationship more complicated than usual. Construction firms’CSR fulfillment serves to engage in reliable relationships with stakeholders and consequently improve CFP. It can bring both benefits and costs to the firm, which suggests that the CSR–CFP relationship is non-linear. This study examines the impacts of CSR on the financial performance of construction firms. We took Chinese-listed construction companies as an example, and an inverted U-shaped curve relationship between CSR and CFP was eventually revealed. Further, the significant moderating role of the degree of corporate internationalization (DOI) in the CSR–CFP relationship is disclosed. The results show that matching a high DOI-high CSR and a low DOI-low CSR is more conducive to CFP promotion. Thus, this research makes contributions to the academic perception of the impacts of CSR and DOI on CFP and provides insights for CSR fulfillment in the international arena.

6.
ACR Open Rheumatol ; 4(3): 238-246, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1565159

ABSTRACT

OBJECTIVE: Patients with immune-mediated diseases treated with anti-CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID-19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown. METHODS: We identified patients with immune-mediated diseases who received anti-CD20 monoclonal antibodies within 1 year prior to the index date of polymerase chain reaction-confirmed COVID-19 between January 31, 2020, and January 31, 2021. General population comparators with COVID-19 were matched up 5:1 by age, sex, and polymerase chain reaction date. Unadjusted and multivariable adjusted (for age, race, body mass index, and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in recipients of anti-CD20 monoclonal antibodies versus comparators were estimated by using Cox regression. RESULTS: We identified 114 cases patients COVID-19 who had received anti-CD20 monoclonal antibodies for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). Patients treated with anti-CD20 monoclonal antibodies had higher mortality (adjusted HR 2.16; 95% CI: 1.03-4.54) than matched comparators. Risks of hospitalization (adjusted HR 0.88; 95% CI: 0.62-1.26) and mechanical ventilation use (adjusted HR 0.82; 95% CI: 0.36-1.87) were similar. Similar trends were seen in analyses according to type of indication (eg, rheumatic or neurologic disease) and duration of anti-CD20 monoclonal antibody use (<1 or ≥1 year) and after patients with interstitial lung disease, those with cancer, and those on glucocorticoids prior to COVID-19 diagnosis were excluded. CONCLUSION: Patients who received anti-CD20 monoclonal antibodies for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in recipients of anti-CD20 monoclonal antibodies during the ongoing pandemic.

7.
Adv Sci (Weinh) ; 8(23): e2102593, 2021 12.
Article in English | MEDLINE | ID: covidwho-1559092

ABSTRACT

Fast and accurate identification of microbial pathogens is critical for the proper treatment of infections. Traditional culture-based diagnosis in clinics is increasingly supplemented by metagenomic next-generation-sequencing (mNGS). Here, RNA/cDNA-targeted sequencing (meta-transcriptomics using NGS (mtNGS)) is established to reduce the host nucleotide percentage in clinic samples and by combining with Oxford Nanopore Technology (ONT) platforms (meta-transcriptomics using third-generation sequencing, mtTGS) to improve the sequencing time. It shows that mtNGS improves the ratio of microbial reads, facilitates bacterial identification using multiple-strategies, and discovers fungi, viruses, and antibiotic resistance genes, and displaying agreement with clinical findings. Furthermore, longer reads in mtTGS lead to additional improvement in pathogen identification and also accelerate the clinical diagnosis. Additionally, primary tests utilizing direct-RNA sequencing and targeted sequencing of ONT show that ONT displays important potential but must be further developed. This study presents the potential of RNA-targeted pathogen identification in clinical samples, especially when combined with the newest developments in ONT.


Subject(s)
Bronchoalveolar Lavage Fluid/microbiology , High-Throughput Nucleotide Sequencing/methods , Infections/genetics , Metagenomics/methods , RNA/genetics , Sequence Analysis, RNA/methods , Aged , Bronchoalveolar Lavage/methods , Female , Humans , Male , Metagenome/genetics , Middle Aged
8.
Arthritis Care Res (Hoboken) ; 74(5): 741-747, 2022 May.
Article in English | MEDLINE | ID: covidwho-1556247

ABSTRACT

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections owing to immunologic dysfunction and use of potent immunomodulatory medications; however, few data are available on their risk of COVID-19. We estimated the rate of COVID-19 among RA participants and compared it with that of the general population. METHODS: Using the Health Improvement Network, we identified RA patients before February 2020 and followed them to September 2020. We calculated the rate of COVID-19 among participants with RA and compared it with that of the general population using a Cox proportional hazards model, adjusting for potential confounders using overlap weighting of exposure score. We repeated the same analysis among participants with osteoarthritis, a nonautoimmune rheumatic disease, as a negative control exposure. RESULTS: We identified 225 cases of suspected and confirmed COVID-19 among 17,268 RA patients, and 14,234 cases among 1,616,600 participants in the general population (1.4 versus 0.9/1,000 person-months), with the adjusted hazard ratio (HRadj ) being 1.19 (95% confidence interval [95% CI] 1.04-1.36). Confirmed COVID-19 cases developed in 46 RA participants and in 2,249 in the general population (0.3 versus 0.1/1,000 person-months), with the HRadj being 1.42 (95% CI 1.01-1.95). No statistically significant difference was observed for suspected and confirmed (HR 1.00 [95% CI 0.93-1.07]) or confirmed (HR 1.08 [95% CI 0.92-1.27]) COVID-19 rates between participants with osteoarthritis and the general population. CONCLUSION: RA, but not osteoarthritis, was associated with an increased risk of COVID-19. Our findings provide timely evidence to support recommendations that booster vaccines and priority access to anti-SARS-CoV-2 monoclonal antibody treatments should be encouraged for RA patients.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Osteoarthritis , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/epidemiology , COVID-19/epidemiology , Cohort Studies , Humans , Osteoarthritis/complications , Osteoarthritis/diagnosis , Osteoarthritis/epidemiology , Proportional Hazards Models
9.
JAMA Netw Open ; 4(10): e2131034, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1482079

ABSTRACT

Importance: Allergic history in individuals with confirmed anaphylaxis to a messenger RNA (mRNA) COVID-19 vaccine is common. However, the risk factors for allergy symptoms after receiving the vaccine are unknown. Objective: To assess the association between self-reported history of high-risk allergy and self-reported allergic reactions after mRNA COVID-19 vaccination of health care employees. Design, Setting, and Participants: This cohort study obtained demographic, medical, and vaccine administration data of employees of Mass General Brigham from the institutional electronic health record. Employees who received at least 1 dose of an mRNA COVID-19 vaccine between December 14, 2020, and February 1, 2021, and who completed at least 1 postvaccination symptom survey in the 3 days after vaccination were included. Exposures: Self-reported history of high-risk allergy, defined as a previous severe allergic reaction to a vaccine, an injectable medication, or other allergen. Main Outcomes and Measures: The primary outcome was 1 or more self-reported allergic reactions in the first 3 days after dose 1 or dose 2 of an mRNA COVID-19 vaccine. Multivariable log binomial regression was used to assess the association between allergic reactions and high-risk allergy status. Results: A total of 52 998 health care employees (mean [SD] age, 42 [14] years; 38 167 women [72.0%]) were included in the cohort, of whom 51 706 (97.6%) received 2 doses of an mRNA COVID-19 vaccine and 474 (0.9%) reported a history of high-risk allergy. Individuals with vs without a history of high-risk allergy reported more allergic reactions after receiving dose 1 or 2 of the vaccine (11.6% [n = 55] vs 4.7% [n = 2461]). In the adjusted model, a history of high-risk allergy was associated with an increased risk of allergic reactions (adjusted relative risk [aRR], 2.46; 95% CI, 1.92-3.16), with risk being highest for hives (aRR, 3.81; 95% CI, 2.33-6.22) and angioedema (aRR, 4.36; 95% CI, 2.52-7.54). Conclusions and Relevance: This cohort study found that self-reported history of high-risk allergy was associated with an increased risk of self-reported allergic reactions within 3 days of mRNA COVID-19 vaccination. However, reported allergy symptoms did not impede the completion of the 2-dose vaccine protocol among a cohort of eligible health care employees, supporting the overall safety of mRNA COVID-19 vaccine.


Subject(s)
COVID-19 Vaccines/adverse effects , Hypersensitivity/epidemiology , Vaccination/statistics & numerical data , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Case-Control Studies , Female , Humans , Hypersensitivity/etiology , Male , Middle Aged , Pandemics , Prospective Studies , Risk Factors , SARS-CoV-2 , Self Report
10.
Front Immunol ; 12: 715464, 2021.
Article in English | MEDLINE | ID: covidwho-1430698

ABSTRACT

The mutants resulted from the ongoing SARS-CoV-2 epidemic have showed resistance to antibody neutralization and vaccine-induced immune response. The present study isolated and identified two novel SARS-CoV-2 neutralizing antibodies (nAbs) from convalescent COVID-19 patients. These two nAbs (XG81 and XG83) were then systemically compared with nine nAbs that were reconstructed by using published data, and revealed that, even though these two nAbs shared targeting epitopes on spike protein, they were different from any of the nine nAbs. Compared with XG81, XG83 exhibited a higher RBD binding affinity and neutralization potency against wild-typed pseudovirus, variant pseudoviruses with mutated spike proteins, such as D614G, E484Q, and A475V, as well as the authentic SARS-CoV-2 virus. To explore potential broadly neutralizing antibodies, heavy and light chains from all 18 nAbs (16 published nAbs, XG81 and XG83) were cross-recombined, and some of the functional antibodies were screened and studied for RBD binding affinity, and neutralizing activity against pseudovirus and the authentic SARS-CoV-2 virus. The results demonstrated that several recombined antibodies had a more potent neutralization activity against variant pseudoviruses compared with the originally paired Abs. Taken together, the novel neutralizing antibodies identified in this study are a likely valuable addition to candidate antibody drugs for the development of clinical therapeutic agents against SARS-CoV-2 to minimize mutational escape.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , Broadly Neutralizing Antibodies/therapeutic use , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/genetics , Antibodies, Viral/therapeutic use , Antibody Affinity/immunology , B-Lymphocytes/immunology , Broadly Neutralizing Antibodies/genetics , COVID-19/immunology , COVID-19/therapy , Cell Line , Epitopes/immunology , Humans , Immunotherapy/methods , Neutralization Tests , SARS-CoV-2/drug effects
11.
ACR Open Rheumatol ; 3(12): 834-841, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1400725

ABSTRACT

OBJECTIVE: To investigate the perceived risk of coronavirus disease 2019 (COVID-19) infection and outcomes as well as shielding practices among patients with rheumatoid arthritis (RA) during the COVID-19 pandemic. METHODS: We surveyed participants with RA in a large health care system between July 16 and November 8, 2020. Participants reported RA treatment, COVID-19 risk perception, and shielding practices (eg, masks, social distancing, and quarantining). We examined the association of demographic and disease-specific factors with risk perception and the association of risk perception with shielding practices. RESULTS: Of 494 participants, 195 (40%), 169 (34%), and 130 (26%) strongly agreed, agreed, or were uncertain/disagreed that their RA put them at higher risk for COVID-19 or poor outcomes, respectively. Younger age (odds ratio [OR]: 0.98), having a comorbidity (OR: 1.60), and biologic disease-modifying antirheumatic drug (bDMARD) use (OR: 1.75) were independently associated with a higher perceived risk. Among those who strongly agreed, agreed, or were uncertain/disagreed that they had greater risk, 165 (85%), 118 (70%), and 69 (53%), respectively, practiced all three shielding measures (P < 0.0001). Those who strongly agreed or agreed that they were at higher risk were more likely to use all three shielding practices (OR: 4.16 and 1.97, respectively). bDMARD use and glucocorticoid use were associated with using all three shielding measures (OR: 1.99 and 1.81, respectively). CONCLUSION: Perception of COVID-19 risk among patients with RA varies substantially. Factors associated with perceived risk are different from those found to be associated with worse outcomes in observational studies. Greater perceived risk is associated with more strict shielding, which has implications for patient education and mental health.

12.
Front Immunol ; 12: 693775, 2021.
Article in English | MEDLINE | ID: covidwho-1394758

ABSTRACT

Small number of SARS-CoV-2 epidemic lineages did not efficiently exhibit a neutralization profile, while single amino acid mutation in the spike protein has not been confirmed in altering viral antigenicity resulting in immune escape. To identify crucial mutations in spike protein that escape humoral immune response, we evaluated the cross-neutralization of convalescent plasmas and RBD-specific monoclonal antibodies (mAbs) against various spike protein-based pseudoviruses. Three of 24 SARS-CoV-2 pseudoviruses containing different mutations in spike protein, including D614G, A475V, and E484Q, consistently showed an altered sensitivity to neutralization by convalescent plasmas. A475V and E484Q mutants are highly resistant to neutralization by mAb B38 and 2-4, suggesting that some crucial mutations in spike protein might evolve SARS-CoV-2 variants capable of escaping humoral immune response.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Substitution/genetics , Amino Acid Substitution/immunology , Antibodies, Neutralizing/immunology , Convalescence , Humans , Immune Evasion , Immunity, Humoral , Neutralization Tests , Protein Binding
13.
Lancet Rheumatol ; 3(9): e638-e647, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1253804

ABSTRACT

BACKGROUND: COVID-19 can induce a hyperinflammatory state, which might lead to poor clinical outcomes. We aimed to assess whether patients with a systemic rheumatic disease might be at increased risk for hyperinflammation and respiratory failure from COVID-19. METHODS: We did a retrospective, comparative cohort study of patients aged 18 years or older admitted to hospital with PCR-confirmed COVID-19 at Mass General Brigham (Boston, USA). We identified patients by a search of electronic health records and matched patients with a systemic rheumatic disease 1:5 to comparators. We compared individual laboratory results by case status and extracted laboratory results and COVID-19 outcomes for each participant. We calculated the COVID-19-associated hyperinflammation score (cHIS), a composite of six domains (a score of ≥2 indicating hyperinflammation) and used logistic regression to estimate odds ratios (ORs) for COVID-19 outcomes by hyperinflammation and case status. FINDINGS: We identified 57 patients with a systemic rheumatic disease and 232 matched comparators who were admitted to hospital with COVID-19 between Jan 30 and July 7, 2020; 38 (67%) patients with a rheumatic disease were female compared with 158 (68%) matched comparators. Patients with a systemic rheumatic disease had higher peak median neutrophil-to-lymphocyte ratio (9·6 [IQR 6·4-22·2] vs 7·8 [4·5-16·5]; p=0·021), lactate dehydrogenase concentration (421 U/L [297-528] vs 345 U/L [254-479]; p=0·044), creatinine concentration (1·2 mg/dL [0·9-2·0] vs 1·0 mg/dL [0·8-1·4], p=0·014), and blood urea nitrogen concentration (31 mg/dL [15-61] vs 23 mg/dL [13-37]; p=0·033) than comparators, but median C-reactive protein concentration (149·4 mg/L [76·4-275·3] vs 116·3 mg/L [58·8-225·9]; p=0·11) was not significantly different. Patients with a systemic rheumatic disease had higher peak median cHIS than comparators (3 [1-5] vs 2 [1-4]; p=0·013). All patients with a peak cHIS of 2 or more had higher odds of admission to intensive care (OR 3·45 [95% CI 1·98-5·99]), mechanical ventilation (66·20 [8·98-487·80]), and in-hospital mortality (16·37 [4·75-56·38]) than patients with a peak cHIS of less than 2. In adjusted analyses, patients with a rheumatic disease had higher odds of admission to intensive care (2·08 [1·09-3·96]) and mechanical ventilation (2·60 [1·32-5·12]) than comparators, but not in-hospital mortality (1.78 [0·79-4·02]). Among patients who were discharged from hospital, risk of rehospitalisation (1·08 [0·37-3·16]) and mortality within 60 days (1·20 [0·58-2·47]) was similar in patients and comparators. INTERPRETATION: Patients with a systemic rheumatic disease who were admitted to hospital for COVID-19 had increased risk for hyperinflammation, kidney injury, admission to intensive care, and mechanical ventilation compared with matched comparators. However, among patients who survived, post-discharge outcomes were not significantly different. The cHIS identified patients with hyperinflammation, which was strongly associated with poor COVID-19 outcomes in both patients with a rheumatic disease and comparators. Clinicians should be aware that patients with systemic rheumatic diseases and COVID-19 could be susceptible to hyperinflammation and poor hospital outcomes. FUNDING: None.

14.
Front Pharmacol ; 12: 602218, 2021.
Article in English | MEDLINE | ID: covidwho-1219417

ABSTRACT

Background: Coronavirus Disease 2019 (COVID-19) is still a relevant global problem. Although some patients have recovered from COVID-19, the sequalae to the SARS-CoV-2 infection may include pulmonary fibrosis, which may contribute to considerable economic burden and health-care challenges. Convalescent Chinese Prescription (CCP) has been widely used during the COVID-19 recovery period for patients who were at high risk of pulmonary fibrosis and is recommended by the Diagnosis and Treatment Protocol for COVID-19 (Trial Version sixth, seventh). However, its underlying mechanism is still unclear. Methods: In this study, an integrated pharmacology approach was implemented, which involved evaluation of absorption, distribution, metabolism and excretion of CCP, data mining of the disease targets, protein-protein interaction (PPI) network construction, and analysis, enrichment analysis, and molecular docking simulation, to predict the bioactive components, potential targets, and molecular mechanism of CCP for pulmonary fibrosis associated with SARS-CoV-2 infection. Results: The active compound of CCP and the candidate targets, including pulmonary fibrosis targets, were obtained through database mining. The Drug-Disease network was constructed. Sixty-five key targets were identified by topological analysis. The findings of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation suggested that the VEGF, Toll-like 4 receptor, MAPK signaling pathway, and TGF-ß1 signaling pathways may be involved in pulmonary fibrosis. In the molecular docking analyses, VEGF, TNF-α, IL-6, MMP9 exhibited good binding activity. Findings from our study indicated that CCP could inhibit the expression of VEGF, TNF-α, IL-6, MMP9, TGF-ß1 via the VEGF, Toll-like 4 receptor, MAPK, and TGF-ß1 signaling pathways. Conclusion: Potential mechanisms involved in CCP treatment for COVID-19 pulmonary fibrosis associated with SARS-CoV-2 infection involves multiple components and multiple target points as well as multiple pathways. These findings may offer a profile for further investigations of the anti-fibrotic mechanism of CCP.

15.
Arthritis Rheumatol ; 73(6): 914-920, 2021 06.
Article in English | MEDLINE | ID: covidwho-1210637

ABSTRACT

OBJECTIVE: Patients with systemic autoimmune rheumatic diseases (ARDs) continue to be concerned about risks of severe coronavirus disease 2019 (COVID-19) outcomes. This study was undertaken to evaluate the risks of severe outcomes in COVID-19 patients with systemic ARDs compared to COVID-19 patients without systemic ARDs. METHODS: Using a large multicenter electronic health record network, we conducted a comparative cohort study of patients with systemic ARDs diagnosed as having COVID-19 (identified by diagnostic code or positive molecular test result) compared to patients with COVID-19 who did not have systemic ARDs, matched for age, sex, race/ethnicity, and body mass index (primary matched model) and additionally matched for comorbidities and health care utilization (extended matched model). Thirty-day outcomes were assessed, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation, acute renal failure requiring renal replacement therapy, ischemic stroke, venous thromboembolism, and death. RESULTS: We initially identified 2,379 COVID-19 patients with systemic ARDs (mean age 58 years; 79% female) and 142,750 comparators (mean age 47 years; 54% female). In the primary matched model (2,379 patients with systemic ARDs and 2,379 matched comparators with COVID-19 without systemic ARDs), patients with systemic ARDs had a significantly higher risk of hospitalization (relative risk [RR] 1.14 [95% confidence interval (95% CI) 1.03-1.26]), ICU admission (RR 1.32 [95% CI 1.03-1.68]), acute renal failure (RR 1.81 [95% CI 1.07-3.07]), and venous thromboembolism (RR 1.74 [95% CI 1.23-2.45]) versus comparators but did not have a significantly higher risk of mechanical ventilation or death. In the extended model, all risks were largely attenuated, except for the risk of venous thromboembolism (RR 1.60 [95% CI 1.14-2.25]). CONCLUSION: Our findings indicate that COVID-19 patients with systemic ARDs may be at a higher risk of hospitalization, ICU admission, acute renal failure, and venous thromboembolism when compared to COVID-19 patients without systemic ARDs. These risks may be largely mediated by comorbidities, except for the risk of venous thromboembolism.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Rheumatic Diseases/epidemiology , SARS-CoV-2 , Acute Kidney Injury/epidemiology , Acute Kidney Injury/virology , Cohort Studies , Comorbidity , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Odds Ratio , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Rheumatic Diseases/virology , Risk Factors , United States/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/virology
16.
Gut Microbes ; 13(1): 1-21, 2021.
Article in English | MEDLINE | ID: covidwho-1121345

ABSTRACT

SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes.


Subject(s)
COVID-19/microbiology , COVID-19/virology , Dysbiosis/diagnosis , Gastrointestinal Microbiome , Virome , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Anti-Bacterial Agents/therapeutic use , COVID-19/therapy , Case-Control Studies , China , Disease Models, Animal , Female , Genome, Viral , Humans , Male , Mice , Mice, Inbred C57BL , MicroRNAs , Middle Aged , Transcriptome
17.
J Asthma ; 59(3): 442-450, 2022 03.
Article in English | MEDLINE | ID: covidwho-1112048

ABSTRACT

OBJECTIVE: The evidence pertaining to the effects of asthma on Coronavirus disease 2019 outcomes has been unclear. To improve our understanding of the clinically important association of asthma and Coronavirus disease 2019. METHODS: A matched cohort study was performed using data from the Mass General Brigham Health Care System (Boston, MA). Adult (age ≥18 years) patients with confirmed Coronavirus disease 2019 and without chronic obstructive pulmonary disease, cystic fibrosis, or interstitial lung disease between March 4, 2020 and July 2, 2020 were analyzed. Up to five non-asthma comparators were matched to each asthma patient based on age (within 5 years), sex, and date of positive test (within 7 days). The primary outcomes were hospitalization, mechanical ventilation, and death, using multivariable Cox-proportional hazards models accounting for competing risk of death, when appropriate. Patients were followed for these outcomes from diagnosis of Coronavirus disease 2019 until July 2, 2020. RESULTS: Among 562 asthma patients, 199 (21%) were hospitalized, 15 (3%) received mechanical ventilation, and 7 (1%) died. Among the 2686 matched comparators, 487 (18%) were hospitalized, 107 (4%) received mechanical ventilation, and 69 (3%) died. The adjusted Hazard Ratios among asthma patients were 0.99 (95% Confidence Internal 0.80, 1.22) for hospitalization, 0.69 (95% Confidence Internal 0.36, 1.29) for mechanical ventilation, and 0.30 (95% Confidence Internal 0.11, 0.80) for death. CONCLUSIONS: In this matched cohort study from a large Boston-based healthcare system, asthma was associated with comparable risk of hospitalization and mechanical ventilation but a lower risk of mortality.


Subject(s)
Asthma/epidemiology , COVID-19/epidemiology , COVID-19/physiopathology , Adult , Age Factors , Aged , Aged, 80 and over , Boston , COVID-19/mortality , Female , Hospitalization , Humans , Male , Middle Aged , Patient Acuity , Proportional Hazards Models , Respiration, Artificial , SARS-CoV-2 , Sex Factors
19.
Journal of Allergy and Clinical Immunology ; 147(2, Supplement):AB241, 2021.
Article in English | ScienceDirect | ID: covidwho-1056748
20.
Lancet Rheumatol ; 3(2): e131-e137, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-989568

ABSTRACT

BACKGROUND: As the COVID-19 pandemic continues worldwide, severe COVID-19 outcomes remain a major concern for patients with rheumatic and musculoskeletal diseases. We aimed to investigate temporal trends in COVID-19 outcomes in patients with rheumatic and musculoskeletal diseases over the course of the pandemic. METHODS: Using a large, multicentre, electronic health record network (TriNetX), we did a comparative cohort study of patients with rheumatic and musculoskeletal diseases who were diagnosed with COVID-19 (by International Classification of Diseases, Tenth Revision code or positive PCR test) during the first 90 days of the pandemic (early cohort) compared with the second 90 days of the pandemic (late cohort), matched (1:1) for demographics, comorbidities, laboratory results, glucocorticoid use, and previous hospitalisations using an exposure score method. Outcomes were assessed within 30 days of COVID-19 diagnosis, including hospitalisation, intensive care unit admission, invasive mechanical ventilation, renal failure, and death. We did a subgroup analysis among patients with rheumatic and musculoskeletal diseases who were hospitalised with COVID-19. FINDINGS: We identified 8540 patients with rheumatic and musculoskeletal diseases who were diagnosed with COVID-19 during the 6-month study period, including 2811 in the early cohort and 5729 in the late cohort. In the exposure score matched analysis, the risk of hospitalisation was lower in the late cohort than in the early cohort (874 [32·4%] of 2701 patients vs 1227 [45·4%] of 2701 patients; relative risk [RR] 0·71, 95% CI 0·67-0·76). The risks of intensive care unit admission (214 [7·9%] vs 385 [14·3%]; RR 0·56, 95% CI 0·47-0·65), mechanical ventilation (96 [3·6%] vs 247 [9·1%]; 0·39, 0·31-0·49), acute kidney injury (372 [13·8%] vs 560 [20·7%]; 0·66, 0·59-0·75), renal replacement therapy (17 [0·6%] vs 32 [1·2%]; 0·53, 0·30-0·96), and death (122 [4·5%] vs 252 [9·3%]; 0·48, 0·39-0·60) were lower in the late cohort compared with the early cohort. Among the hospitalised subgroup, the risk of the composite outcome of intensive care unit admission, mechanical ventilation, and death was lower in the late cohort than in the early cohort (334 [30·7%] of 1089 patients vs 450 [41·3%] of 1089 patients; RR 0·74, 95% CI 0·67-0·83). INTERPRETATION: The risks of severe COVID-19 outcomes have improved over time in patients with rheumatic and musculoskeletal disease but remain substantial. These findings might reflect ascertainment of milder cases in the later cohort and improvements in treatment and supportive care. FUNDING: None.

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