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1.
Journal of the American College of Cardiology ; 79(9):1784-1784, 2022.
Article in English | Web of Science | ID: covidwho-1849088
3.
Sci Rep ; 11(1): 23561, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1559302

ABSTRACT

N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.


Subject(s)
Glycopeptides/analysis , Mass Spectrometry/methods , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/virology , Chromatography, High Pressure Liquid , Glycosylation , Humans , Mutation , Protein Binding , Protein Structure, Tertiary , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry
4.
Sci Rep ; 11(1): 12330, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1265968

ABSTRACT

SARS-CoV-2 emerged in late 2019 and has since spread around the world, causing a pandemic of the respiratory disease COVID-19. Detecting antibodies against the virus is an essential tool for tracking infections and developing vaccines. Such tests, primarily utilizing the enzyme-linked immunosorbent assay (ELISA) principle, can be either qualitative (reporting positive/negative results) or quantitative (reporting a value representing the quantity of specific antibodies). Quantitation is vital for determining stability or decline of antibody titers in convalescence, efficacy of different vaccination regimens, and detection of asymptomatic infections. Quantitation typically requires two-step ELISA testing, in which samples are first screened in a qualitative assay and positive samples are subsequently analyzed as a dilution series. To overcome the throughput limitations of this approach, we developed a simpler and faster system that is highly automatable and achieves quantitation in a single-dilution screening format with sensitivity and specificity comparable to those of ELISA.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , SARS-CoV-2/isolation & purification , Animals , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/immunology , COVID-19 Serological Testing/economics , COVID-19 Serological Testing/methods , Enzyme-Linked Immunosorbent Assay/economics , Enzyme-Linked Immunosorbent Assay/methods , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Mice , SARS-CoV-2/immunology
5.
Global Advances in Health and Medicine ; 10:22-23, 2021.
Article in English | EMBASE | ID: covidwho-1234511

ABSTRACT

Objective: Integrative medicine is a key framework for the treatment of chronic medical conditions, particularly chronic pain. In-person visits pose notable barriers for individuals with pain or limited mobility, particularly in rural or underserved areas. However, many barriers are pertinent to the expansion of telehealth use in integrative medicine settings, such as concerns about maintaining patient-clinician rapport in the delivery of holistic, relationship-based care. The COVID-19 pandemic served as impetus for an immediate and complete transition to telehealth services in this interdisciplinary outpatient integrative medicine clinic. This poster will present rich qualitative perspectives from multiple stakeholder levels on the experience of virtual visits to examine whether telehealth represents an acceptable, accessible, and high-quality option for providing integrative healthcare. Methods: Patients (N=180), providers (N=19), and administrative staff (N=7) in our outpatient integrative health clinic were surveyed about their experience of providing or receiving care via telehealth. Specifically, participants were asked to describe what telehealth visits were like in comparison to in-person visits. Free-text responses were analyzed for major and minor emergent themes. Results: Major themes identified from the data included acceptability, ease/convenience, comfort, interpersonal connection, technology difficulties, application of telehealth to group/movement classes, and equity/access. Overwhelmingly, participants described telehealth as an acceptable and adequate, at times equal or superior, alternative to in-person visits. Importantly, telehealth improved comfort for patients who could hold visits at home where they were most comfortable. Challenges were also welldescribed including technological issues and loss of interpersonal connection. Conclusion: Telehealth visits represent an acceptable, at times preferable, way to deliver care in an outpatient integrative medicine setting. Telehealth represents a particularly promising care modality for patients experiencing chronic pain or limited mobility, or those residing in rural and underserved communities. Detailed qualitative results provide rich perspective to inform future implementation and health policy regarding telehealth use.

6.
Global Advances in Health and Medicine ; 10:21-22, 2021.
Article in English | EMBASE | ID: covidwho-1234506

ABSTRACT

Objective: Interdisciplinary integrative medicine is key to treatment of chronic pain conditions. In-person visits can burden this population, particularly in rural and underserved areas with limited transportation options. Telehealth visits, were historically unsupported by payment models, delivery platforms, health and technological literacy, and clinician buy-in. The COVID-19 pandemic initiated a rapid transition to telehealth at our interdisciplinary outpatient integrative medicine center. This poster will describe the quantitative experience of telehealth integrative medicine services among stakeholders. Methods: Patients (n=472), clinicians (n=25), and staff (n=12) ranked telehealth vs in-person visits by survey with custom scale quality judgments and discrete choice after transitioning to telehealth and three months later. Results: Patient quality judgements significantly favored telehealth at baseline, B=.77 [0.29-1.25], SE=.25, t(712)= 3.15, p=.002, and increased in preference for telehealth at three months, B=.27 [-0.03-0.57], SE=.15, t(712)= 1.76, p=.079. Quality of technology, residing outside the county, and experiencing multiple disciplines predicted patient telehealth favorability. Clinicians did not favor one modality over the other, B=-1.00 [-1.56--0.44], SE=.29, t(799)=-3.48, p<.001. Patient discrete choice split at baseline and favored telehealth at three months. Overall, discrete choice favored telehealth at follow-up across clinicians and patients. Administrative staff's overall impression of telehealth was most favorable of all groups. Conclusion: Telehealth is a promising care modality for patients experiencing chronic pain. Far from a temporary preference, after three months, the majority of patients indicated they would choose telehealth visits over inperson visits, if they were equally safe. Policy that does not support telehealth for outpatient integrative medicine cannot do so under the name of patient preference, perceptions of quality, patient choice, or access.

7.
Journal of the American College of Cardiology ; 77(18):1883, 2021.
Article in English | EMBASE | ID: covidwho-1223041

ABSTRACT

Background May-Thurner syndrome and pregnancy are independent risk factors for the development of deep vein thrombosis (DVT). Emerging data suggests an association for venous thromboembolism (VTE) development in COVID-19 patients. Treatments for DVT vary and include thrombolysis, mechanical thrombectomy and long-term anticoagulation. We describe a unique case of this in a postpartum female. Case A 31 year old female G3P0121 and recent cesarean section 1 month ago presented with left lower extremity swelling, severely limited ambulation and 3+ edema of the left leg extending to the hip without any right leg edema. She was COVID-19 antibody positive. Occlusive DVTs were confirmed via venous duplex ultrasound and computed tomographic venography of the abdomen and pelvis, extending from distal inferior vena cava to the left popliteal vein. Decision-making Invasive venography confirmed the non-invasive imaging findings. After administering 12-14 mg of tissue plasminogen activator (tPA), multiple aspirations were performed using a rheolytic thrombectomy catheter. However persistent dense thrombus in the iliac and femoral veins remained, thus subsequent balloon angioplasty was performed but unsuccessful. Intravascular ultrasound confirmed the presence of May-Thurner syndrome at the junction of the left common iliac vein and the inferior vena cava. Finally an infusion catheter was placed for tPA. Within 48 hours, patient developed oliguric renal failure likely due to a combination of contrast-induced and pigment nephropathy requiring intermittent hemodialysis. Repeat ultrasound showed resolution of DVT along with improving edema and renal function. Warfarin was chosen for long-term anticoagulation due to renal failure and breast-feeding. Conclusion Pregnancy is a pro thrombotic state that may lead to VTE even in the postpartum period. Decision-making and treatment in these patients may be complex and require a multidisciplinary approach.

8.
Sci Rep ; 11(1): 9682, 2021 05 06.
Article in English | MEDLINE | ID: covidwho-1219072

ABSTRACT

The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Animals , COVID-19/diagnosis , COVID-19 Serological Testing , Epitopes/immunology , Female , Humans , Immunization , Mice , Mice, Inbred BALB C , Models, Molecular , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology
10.
Nat Biotechnol ; 39(6): 717-726, 2021 06.
Article in English | MEDLINE | ID: covidwho-1065901

ABSTRACT

Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections.


Subject(s)
COVID-19/therapy , Influenza, Human/therapy , RNA, Messenger/pharmacology , SARS-CoV-2/genetics , Animals , COVID-19/genetics , COVID-19/virology , CRISPR-Cas Systems/genetics , Cricetinae , Disease Models, Animal , Humans , Influenza, Human/genetics , Influenza, Human/virology , Mice , Orthomyxoviridae/drug effects , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , RNA, Messenger/genetics , RNA, Viral/genetics , Respiratory System/drug effects , Respiratory System/metabolism , SARS-CoV-2/pathogenicity
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