Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
2.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-336963

ABSTRACT

Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein beta 2 -microglobulin (beta 2 m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those containing viral peptides can be detected by CD8 + T lymphocytes that kill infected cells. Many viruses enhance their in vivo survival by encoding genes that downregulate MHC-I expression to avoid CD8 + T cell recognition. Here we report that two accessory proteins encoded by SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, downregulate MHC-I expression using distinct mechanisms. One, ORF3a, a viroporin, reduces global trafficking of proteins, including MHC-I, through the secretory pathway. The second, ORF7a, interacts specifically with the MHC-I heavy chain, acting as a molecular mimic of beta 2 m to inhibit its association. This slows the exit of properly assembled MHC-I molecules from the endoplasmic reticulum. We demonstrate that ORF7a reduces antigen presentation by the human MHC-I allele HLA-A*02:01. Thus, both ORF3a and ORF7a act post-translationally in the secretory pathway to lower surface MHC-I expression, with ORF7a exhibiting a novel and specific mechanism that allows immune evasion by SARS-CoV-2. Significance Statement: Viruses may down-regulate MHC class I expression on infected cells to avoid elimination by cytotoxic T cells. We report that the accessory proteins ORF7a and ORF3a of SARS-CoV-2 mediate this function and delineate the two distinct mechanisms involved. While ORF3a inhibits global protein trafficking to the cell surface, ORF7a acts specifically on MHC-I by competing with beta 2 m for binding to the MHC-I heavy chain. This is the first account of molecular mimicry of beta 2 m as a viral mechanism of MHC-I down-regulation to facilitate immune evasion.

3.
Journal of Heart and Lung Transplantation ; 41(4):S325-S326, 2022.
Article in English | Web of Science | ID: covidwho-1849073
5.
Journal of the American College of Cardiology ; 79(9):2389-2389, 2022.
Article in English | Web of Science | ID: covidwho-1848563
6.
Journal of the American College of Cardiology ; 79(9):2130-2130, 2022.
Article in English | Web of Science | ID: covidwho-1848477
7.
Journal of Electronic Commerce Research ; 23(2):115-137, 2022.
Article in English | Scopus | ID: covidwho-1843208

ABSTRACT

Social commerce has been seeing exponential growth due to the COVID-19 pandemic, which brought a wave of cross-border commerce as consumers purchase more items online. Business uses social media to reach new markets by accessing potential global buyers, expanding their target markets, and increasing brand popularity. Cross-border ecommerce studies showed that perceived risk is a critical factor that reduces individuals’ willingness to purchase unfamiliar foreign products. We introduced an emerging business model, cross-border social commerce (CBSC) and examined the mitigation of perceived risk through trust transfer in a CBSC context. To capture consumers’ purchase intention of cross-border commerce, we conducted an online scenario-based survey. Survey respondents comprising a total of 321 social media users in Indonesia were observed. The results demonstrate that consumers’ trust can be transferred from friends and platforms to brands, and the transfer effect is contingent on the popularity of the brand. Our findings have crucial implications for trust transfer and cross-border social commerce. This study contributes to academia by introducing a new business model and advancing our understanding of how to enhance trust and mitigate risk. Practitioners can gain insight into trust building in CBSC context. © 2022. Journal of Electronic Commerce Research. All Rights Reserved.

8.
Journal of Heart & Lung Transplantation ; 41(4):S325-S326, 2022.
Article in English | Academic Search Complete | ID: covidwho-1783364

ABSTRACT

The American Society of Transplantation and the International Society of Heart and Lung Transplantation recommend COVID-19 vaccination of transplant candidates to maximize immunity, as vaccination after initiation of immunosuppression may confer only partial immunity. However, there are concerns about the impact of vaccine-induced systemic inflammatory responses in critically ill patients with variable hemodynamic states. We aim to explore the safety of pre-transplant vaccination by examining the immediate impact of COVID-19 vaccination on the hemodynamics of hospitalized patients awaiting transplant. A retrospective chart review at a major transplant center was conducted among all heart transplant recipients from January 2021 through September 2021 who were hospitalized and listed or under consideration for listing for transplant at the time of COVID-19 vaccination. Primary outcomes included vital signs, hemodynamic parameters from pulmonary artery catheter-derived measurements, and changes in inotrope/vasopressor infusion rates. Data were extracted at fixed time points 24 hours before and up to 72 hours after vaccination. Given the small sample size and exploratory study nature, only univariate analysis was performed. Of the 50 patients who received heart transplants at our center from January 2021 through September 2021, 37 patients were vaccinated against COVID-19. 13 of those patients were vaccinated before transplant while hospitalized, and 10 of those 13 patients had a pulmonary artery catheter in place at the time of immunization. No significant changes in vital signs (blood pressure, heart rate), hemodynamics (cardiac index, pulmonary artery pressures, systemic vascular resistance), or vasopressor/inotrope infusion rates were observed after vaccination. In this exploratory review of COVID-19 vaccination in heart transplant candidates, we did not detect any notable changes to hemodynamics in the first 72 hours after immunization. Although further investigative research is needed to assess COVID-19 vaccine safety comprehensively in patients with advanced heart failure, the absence of notable hemodynamic changes in this cohort of heart transplant candidates encourages the continued use of COVID-19 vaccination among hospitalized patients with advanced heart failure who are awaiting transplant. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. 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.)

9.
Journal of Heart & Lung Transplantation ; 41(4):S118-S119, 2022.
Article in English | Academic Search Complete | ID: covidwho-1783349

ABSTRACT

A link between SARS-CoV2 infection and myocardial injury has been described. Our center utilizes non-invasive surveillance with gene expression profiling and donor-derived cell-free DNA (dd-cfDNA) in heart transplant (HTx) patients who are either stable or in whom invasive surveillance is contraindicated. We evaluated whether HTx recipients diagnosed with SARS-CoV2 infection demonstrated evidence of myocardial allograft injury using dd-cfDNA. HTx recipients were included if they had dd-cfDNA testing (AlloSure;CareDx Inc., Brisbane, CA) within 60 days of their initial SARS-CoV2 diagnosis. Data on hospitalization, therapy, and clinical outcomes was captured. Dd-cfDNA results at the assay limit of detection (LOD, <0.12%) were set equal to the LOD. Between 3/2020 and 6/2021, we identified 12 HTx recipients with SARS-CoV2 and dd-cfDNA results within the specified time period;median age was 55 (IQR 28 - 64.5) with infection occurring 506.5 days (IQR 176 - 803.5) after transplant. Mean dd-cfDNA was 0.13 ± 0.03%, assessed 26 (IQR 20 - 35) days after infection. Prior results, available for 9 patients and obtained a median of 33 (IQR 27 - 59) days prior to infection, did not differ from post-infection values (0.13 ± 0.02%, p = 0.66). Following diagnosis, 8 (67%) patients were hospitalized;5 had mycophenolate held, 2 received steroids, 2 received convalescent plasma, 4 received remdesivir, and 1 received monoclonal Ab therapy. At a median follow-up time of 304 (IQR 212.5 - 331) days after diagnosis, all twelve patients were alive with good allograft function (mean ejection fraction 59 ± 4.8%);interval clinically-relevant immunologic outcomes included one episode of rejection (pAMR1) and three (25%) findings of de novo donor-specific antibodies (dnDSA). In this single-center pilot study assessing myocardial injury among HTx recipients within 2 months of SARS-CoV2 infection, the majority of patients had low dd-cfDNA results (<0.15%) and demonstrated good intermediate-term (6-12 months) graft function. While limited by sample size and protocol-based inclusion criteria, our findings suggest that sustained myocardial injury in HTx recipients after SARS-CoV2 infection may not be common. The impact of SARS-CoV2 infection on immunologic outcomes including rejection and dnDSA in this population merit further study. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. 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.)

10.
Journal of Clinical Oncology ; 40(6 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779694

ABSTRACT

Background: Short-term effectiveness of COVID-19 vaccination is widely demonstrated, but the emerging real-world data suggest that immunity may wane over-time (Levin et al. NEJM 2021). Herein we aimed to explore the long-term efficacy of the COVID-19 vaccination among pts with genitourinary cancer. Methods: In this study, pts with genitourinary malignancies (prostate, kidney, and bladder cancers) who had not received COVID-19 vaccination were included. Blood samples were collected prior to and after one dose of either an adenovirus- or mRNA-based COVID-19 vaccine at the 2- and 6-month timepoints. Additional blood samples from pts receiving systemic treatment were collected at 3 consecutive therapy cycles following vaccination. Antibody titers were assessed using the SCoV-2 Detect IgG ELISA assay and results were reported as immune status ratios (ISR). T-cell receptor (TCR) repertoire sequencing was performed using the MiXCR software (MiLabs) and custom strips were used to assess TCR abundance and homology clustering. Results: A total of 183 pts were enrolled, and 136 pts provided baseline blood samples. Among these, 59 (8:51 F:M) provided samples for both the 2-and 6-month timepoints by the 10/6/2021 data cut-off. In this subset of pts, median age was 66 (range 48-85) and 33 (55.9%), 25 (42.4%), and 1 (1.7%) pts had prostate, kidney, and bladder cancer, respectively. A majority of the pts (93.2%) were on systemic treatment with 23.7% on immune checkpoint inhibitors, 18.6% on targeted agents, and 1.7% on chemotherapy. The most commonly administered vaccines were BNT162b2 (61.0%) followed by mRNA-1273 (37.3%) and Ad26.COV2.S (1.7%). The mean (±standard deviation) ISR values at baseline and 2 months were 0.68±1.59 and 6.62±1.75, respectively. At the 6-month timepoint, mean ISR was 5.46±1.61;this was significantly lower than the 2-month antibody titers (p < 0.0001), and reflects a reduction of 17.6%. Further data on TCR sequencing will be presented at the meeting. Conclusions: To our knowledge, this is the first data assessing the long-term serologic outcomes of COVID-19 vaccination in pts with cancer. Our data suggest waning immunity over time in cancer pts. Strategies to prolong host immunity against SARS COV-2 (e.g., booster vaccination) are likely warranted.

11.
Morbidity and Mortality Weekly Report ; 70(35):1228-1232, 2021.
Article in English | GIM | ID: covidwho-1601786

ABSTRACT

What is already known about this topic? Viral infections are a common cause of myocarditis. Some studies have indicated an association between COVID-19 and myocarditis. What is added by this report? During March 2020-January 2021, patients with COVID-19 had nearly 16 times the risk for myocarditis compared with patients who did not have COVID-19, and risk varied by sex and age. What are the implications for public health practice? These findings underscore the importance of implementing evidence-based COVID-19 prevention strategies, including vaccination, to reduce the public health impact of COVID-19 and its associated complications.

12.
Morbidity and Mortality Weekly Report ; 70(36):1249-1254, 2021.
Article in English | GIM | ID: covidwho-1573388

ABSTRACT

What is already known about this topic? Severe illness from COVID-19 can and does occur in children and adolescents. What is added by this report? COVID-19 cases, emergency department visits, and hospital admissions increased from June to August 2021 among persons aged 0-17 years. Emergency department visits and hospital admissions in a 2-week period in August 2021 were higher in states with lower population vaccination coverage and lower in states with higher vaccination coverage. What are the implications for public health? Community vaccination, in coordination with testing strategies and other prevention measures, is critical to protecting pediatric populations from SARS-CoV-2 infection and severe COVID-19.

14.
American Journal of Cancer Research ; 11(10):4994-5005, 2021.
Article in English | EMBASE | ID: covidwho-1498709

ABSTRACT

SARS-CoV-2 exploits the host cellular machinery for virus replication leading to the acute syndrome of coronavirus disease 2019 (COVID-19). Growing evidence suggests SARS-CoV-2 also exacerbates many chronic diseases, including cancers. As mutations on the spike protein (S) emerged as dominant variants that reduce vaccine efficacy, little is known about the relation between SARS-CoV-2 virus variants and cancers. Compared to the SARS-CoV-2 wild-type, the Gamma variant contains two additional NXT/S glycosylation motifs on the S protein. The hyperglycosylated S of Gamma variant is more stable, resulting in more significant epithelial-mesenchymal transition (EMT) potential. SARS-CoV-2 infection promoted NF-κB signaling activation and p65 nuclear translocation, inducing Snail expression. Pharmacologic inhibition of NF-κB activity by nature food compound, I3C suppressed viral replication and Gamma variant-mediated breast cancer metastasis, indicating that NF-κB inhibition can reduce chronic disease in COVID-19 patients. Our study revealed that the Gamma variant of SARS-CoV-2 activates NF-κB and, in turn, triggers the pro-survival function for cancer progression.

15.
Annals of Oncology ; 32:S1132, 2021.
Article in English | EMBASE | ID: covidwho-1432858

ABSTRACT

Background: Preliminary studies have characterized potential adverse effects associated with COVID-19 vaccination in pts with cancer. However, biological characterization of vaccine response has yet to be performed. Methods: Eligible pts with advanced GU cancers (metastatic/unresectable prostate, bladder and renal cell carcinoma [RCC]) and had not yet received COVID-19 vaccination. Pts were consented to receive sequential blood draws prior to vaccination and at landmarks of 2, 6, and 12 mos following vaccination. Pts on systemic treatment had additional blood draws coinciding with their first 3 cycles of therapy following vaccination. Ab titers to SARS-CoV-2 were quantified via ELISA and reported as an immune status ratio (ISR). RNA was extracted from PBMC aliquots, converted into cDNA and TCR α/β sequences were selectively amplified. TCR abundance and homology clustering was performed using custom scripts. Results: As of May 14, 2021, 130 pts had consented to the study of whom 126 pts submitted baseline (BL) specimens. The current analysis focuses on 56 pts who submitted cycle 1 (C1) specimens. Among these, 29, 26, and 1 pts had RCC, prostate and bladder cancer, respectively;19 were on checkpoint inhibitor (CPI)-based regimens while 37 were on non-CPI regimens. BNT162b2 (Pfizer) was the most commonly administered vaccine in the cohort (n=29), followed by mRNA-1273 (Moderna;n=26). COVID-19 Ab titers increased significantly from BL to C1 across the cohort from 0.19 (interquartile range [IQR] 0.12-0.18) to 4.37 (IQR 0.2-6.60;P<0.0001). However, 8/56 pts (14.3%) receiving CPI-based regimens and 8/56 pts (14.3%) receiving non-CPI-based regimens were noted to have negative Ab titers after a median of 18 and 35 days following initial vaccination, respectively. No significant difference was observed in the increase from BL to C1 in pts receiving CPI vs non-CPI-based regimens. Specimen collection is ongoing;updated Ab titer data and TCR sequencing data will be presented. Conclusions: Our data prompt concern for delayed or insufficient COVID-19 Ab response in a subset of pts with advanced GU cancers. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: R. Salgia: Non-Financial Interests, Personal, Advisory Board: Janssen;Non-Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Advisory Board: Merck;Non-Financial Interests, Personal, Advisory Board: Novartis. S.K. Pal: Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: Medivation;Financial Interests, Personal, Invited Speaker: Astellas Pharma;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Aveo;Financial Interests, Personal, Advisory Board: Myriad;Non-Financial Interests, Personal, Other: Genentech;Non-Financial Interests, Personal, Other: Exelixis;Non-Financial Interests, Personal, Other: BMS;Non-Financial Interests, Personal, Other: Astellas Pharma;Financial Interests, Institutional, Funding: Medivation. All other authors have declared no conflicts of interest.

17.
Investigative Ophthalmology and Visual Science ; 62(8), 2021.
Article in English | EMBASE | ID: covidwho-1378809

ABSTRACT

Purpose : While one might expect that universal masking would decrease the risk of oral flora contamination during the injection procedure, anecdotal reports of oral flora-related endophthalmitis during COVID-19 have emerged. We performed a prospective observational cohort study to determine the effect of taping the top of face masks on air particle counts directed toward the eye during simulated intravitreal injections. Methods : Thirteen healthy N95 qualitative fit tested human subjects were recruited, three women and ten men, with an age range of [24, 35]. Each wore a cloth, surgical, or N95 mask in randomized order. The number of air particles were quantified using a particle counter suspended over the right eye while each subject breathed normally, deeply, or spoke using a standardized script. Particle counts were obtained with the top of each mask taped and untaped. The main outcome measurements were particle counts in the size classes of 0.3 mm, 0.5 mm, 1 mm, 3 mm, 5 mm, 10 mm, and total particle count. The Wilcoxon signed rank test was used to test for paired differences between taped and untaped particle counts for each combination of mask type and respiratory mode, at each particle size. Results : Taping cloth masks while subjects were speaking significantly reduced particle counts for the size classes of 0.3 mm (p=0.03), 0.5 mm (p=0.01), 1 mm (p=0.03), and total particle counts (p=0.008) compared to no taping. Taping the top of cloth masks during normal or deep breathing did not significantly affect particle counts compared to no taping. Taping the top of surgical or N95 masks did not significantly alter particle counts for any breathing condition tested. Conclusions : Taping the top of cloth masks prior to simulated intravitreal injections significantly reduced air particle counts directed toward the eye when subjects were speaking compared to no taping. This may have implications for decreasing air particles reaching the eye during intravitreal injections, including aerosolized droplets from a patient's mouth that may carry oral pathogens.

18.
S D Med ; 74(4):182-183, 2021.
Article in English | PubMed | ID: covidwho-1371145
19.
American Journal of Cancer Research ; 11(5):2278-2290, 2021.
Article in English | EMBASE | ID: covidwho-1250384

ABSTRACT

The engagement of human angiotensin-converting enzyme 2 (hACE2) and SARS-CoV-2 spike protein facilitate virus spread. Thus far, ACE2 and TMPRSS2 expression is correlated with the epithelial-mesenchymal transition (EMT) gene signature in lung cancer. However, the mechanism for SARS-CoV-2-induced EMT has not been thoroughly explored. Here, we showed that SARS-CoV-2 induces EMT phenotypic change and stemness in breast cancer cell model and subsequently identified Snail as a modulator for this regulation. The in-depth analysis identifies the spike protein (S), but not envelope (E), nucleocapsid (N), or membrane protein (M), of SARS-CoV-2 induces EMT marker changes. Suppression of Snail expression in these cells abrogates S protein-induced invasion, migration, stemness, and lung metastasis, suggesting that Snail is required for SARS-CoV-2-mediated aggressive phenotype in cancer. This study reveals an important oncogenic role of SARS-CoV-2 in triggering breast cancer metastasis through Snail upregulation.

20.
Open Forum Infectious Diseases ; 7(SUPPL 1):S325, 2020.
Article in English | EMBASE | ID: covidwho-1185880

ABSTRACT

Background: The coronavirus-19-disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to >200 countries and surpassed 7 million cases. There is a broad range of COVID-19 illness, ranging from milder disease to a rapidly progressive respiratory disease and ARDS. The causes of this different clinical course and the drivers for severe disease are currently unknown. A fulminant increase of pro-inflammatory cytokines is thought to play a role in causing a rapid disease evolution, however the immune correlates of severe COVID-19 remain unclear. Methods: To gain insight into relationship between immune responses and disease severity we built a longitudinal cohort of 40 adult patients with known COVID- 19. Samples were collected at diagnosis and every 7 days until hospital discharge or death. As controls we also included a group of convalescent patients, and subjects who tested negative for COVID-19 by PCR. Clinical and laboratory data and were also collected. Multicolor flow cytometry was used to determine the presence and phenotype of B, T and natural killer (NK) cells. We also identified specific sub-populations (Tfh, activated/cytotoxic CD8 and NK) and assessed lymphoid exhaustion of different cell types such as naïve, memory T cells, or NK over time. Anti-Sars-CoV2 IgG and IgM antibody were detected using lateral flow method. Results: We found that the absolute number of lymphocytes and monocytes was decreased starting at diagnosis and correlated with disease severity. Disease severity correlated with decreased NK and T cell. In severe COVID-19 cases, NK cell populations were strongly decreased over time in intubated patients while they recovered in patients who improved and were discharged. CD8+ were also decreased at disease onset and seemed to correlate with disease severity. A high percentage of CD4+ and CD8+ T cells showed an exhausted phenotype. All patients tested at admission had IgM antibody responses irrespective of the course of the disease. Further analyses are ongoing. Conclusion: The characterization and role of the immune responses in COVID- 19 evolution is still under investigation. Further characterization of viral and immune factors will help in identifying subjects at high risk of severe disease and targets for intervention.

SELECTION OF CITATIONS
SEARCH DETAIL