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1.
Value in Health ; 26(6 Supplement):S33, 2023.
Article in English | EMBASE | ID: covidwho-20233097

ABSTRACT

Objectives: To describe and compare real-world outcomes for patients with mild-to-moderate COVID-19 at high risk for progression to severe COVID-19, treated with sotrovimab versus untreated. Method(s): Electronic health records from the National COVID Cohort Collaborative were used to identify US patients (aged >=12 years) diagnosed with COVID-19 (positive test or ICD-10: U07.1) in an ambulatory setting (26 May 2021-30 April 2022) who met Emergency Use Authorization high-risk criteria. Patients receiving the monoclonal antibody (mAb) sotrovimab within 10 days of diagnosis were assigned to the sotrovimab cohort with an index date on the day of infusion. Untreated patients (no evidence of early mAb treatment or prophylaxis mAb or oral antiviral treatment) were assigned to the untreated cohort with an imputed index date based on the time distribution between diagnosis and sotrovimab infusion for the sotrovimab cohort. The primary endpoint was hospitalization or death (both all-cause) within 29 days of index, reported as descriptive rates and adjusted (via inverse-probability-of-treatment weighting [IPTW]) odds ratios (OR) and 95% confidence intervals (CI). Result(s): Of nearly 2.9 million patients diagnosed with COVID-19 during the analysis time period, 4,992 met the criteria for the sotrovimab cohort and 541,325 were included in the untreated cohort. Patients in the sotrovimab cohort were older (60 versus 54 years), more likely to be male (40% versus 38%) and White (85% versus 75%), and met more EUA criteria (3 versus 2) versus the untreated cohort. The 29-day hospitalization or mortality rates were 3.5% (176/4,992) and 4.5% (24,163/541,325) in the sotrovimab and untreated cohorts respectively (unadjusted OR [95% CI]: 0.77 [0.67,0.90];p=0.001;IPTW-adjusted OR [95% CI]: 0.74 [0.61,0.91];p=0.004). Conclusion(s): Sotrovimab demonstrated clinical effectiveness in preventing severe outcomes (hospitalization, mortality) between 26 May 2021-30 April 2022, which included the Delta variant and early surge of Omicron BA.1/BA.2. Funding(s): GSK (Study 219020)Copyright © 2023

2.
American Journal of Respiratory and Critical Care Medicine ; 206(8):961-972, 2022.
Article in English | CAB Abstracts | ID: covidwho-2264829

ABSTRACT

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2;inactivated viral particles;or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.

3.
Smart Health (Amst) ; 26: 100329, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2069687

ABSTRACT

With the emergence of the COVID-19 pandemic, early diagnosis of lung diseases has attracted growing attention. Generally, monitoring the breathing sound is the traditional means for assessing the status of a patient's respiratory health through auscultation; for that a stethoscope is one of the clinical tools used by physicians for diagnosis of lung disease and anomalies. On the other hand, recent technological advances have made telehealth systems a practical and effective option for health status assessment and remote patient monitoring. The interest in telehealth solutions have further grown with the COVID-19 pandemic. These telehealth systems aim to provide increased safety and help to cope with the massive growth in healthcare demand. Particularly, employing acoustic sensors to collect breathing sound would enable real-time assessment and instantaneous detection of anomalies. However, existing work focuses on autonomous determination of respiratory rate which is not suitable for anomaly detection due to inability to deal with noisy data recording. This paper presents a novel approach for effective breathing sound analysis. We promote a new segmentation mechanism of the captured acoustic signals to identify breathing cycles in recorded sound signals. A scoring scheme is applied to qualify the segment based on the targeted respiratory illness by the overall breathing sound analysis. We demonstrate the effectiveness of our approach via experiments using published COPD datasets.

4.
Clin Transl Immunology ; 11(8): e1411, 2022.
Article in English | MEDLINE | ID: covidwho-1990444

ABSTRACT

Objectives: The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs). Methods: We analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant in 113 SOTRs, of whom 44 had recovered from COVID-19 (recovered-SOTRs) and 69 had not contracted the virus (COVID-naïve). In addition, 30 HCs, 8 of whom had recovered from COVID-19, were also studied. Results: Here, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti-viral antibodies against all viral strains in the fully vaccinated COVID-naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti-RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered-SOTRs who received two doses of vaccine demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. Conclusion: These findings illustrate a significant impact of previous infection on the development of anti-SARS-CoV-2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.

6.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.04.13.22273829

ABSTRACT

The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). Although a 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, its effectiveness was still largely unknown. We analyzed 113 vaccinated SOTRs, and 30 healthy controls (HCs), some of whom had recovered from COVID, for their immune responses against the original vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant. Here, we report that 3 doses of the mRNA vaccine had only a modest effect in eliciting anti-viral responses against all viral strains in the fully vaccinated SOTRs who did not contract the virus. Only 34.0% (16/47) of this group of patients demonstrated both detectable anti-RBD IgG and neutralization activities against alpha, beta, and delta variants, and only 8.5% (4/47) of them showed additional omicron-neutralizing capacities. In contrast, 79.5% (35/44) of the vaccinated recovered-SOTRs demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. These findings illustrate a significant impact of previous infection on the development of anti-COVID immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.


Subject(s)
COVID-19
7.
J Acoust Soc Am ; 151(2): 1033, 2022 02.
Article in English | MEDLINE | ID: covidwho-1723417

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide with over 3 × 106 deaths in 2019. Such an alarming figure becomes frightening when combined with the number of lost lives resulting from COVID-caused respiratory failure. Because COPD exacerbations identified early can commonly be treated at home, early symptom detections may enable a major reduction of COPD patient readmission and associated healthcare costs; this is particularly important during pandemics such as COVID-19 in which healthcare facilities are overwhelmed. The standard adjuncts used to assess lung function (e.g., spirometry, plethysmography, and CT scan) are expensive, time consuming, and cannot be used in remote patient monitoring of an acute exacerbation. In this paper, a wearable multi-modal system for breathing analysis is presented, which can be used in quantifying various airflow obstructions. The wearable multi-modal electroacoustic system employs a body area sensor network with each sensor-node having a multi-modal sensing capability, such as a digital stethoscope, electrocardiogram monitor, thermometer, and goniometer. The signal-to-noise ratio (SNR) of the resulting acoustic spectrum is used as a measure of breathing intensity. The results are shown from data collected from over 35 healthy subjects and 3 COPD subjects, demonstrating a positive correlation of SNR values to the health-scale score.


Subject(s)
COVID-19 , Wearable Electronic Devices , Acoustics , COVID-19/diagnosis , Humans , SARS-CoV-2 , Spirometry
8.
Advanced Sciences and Technologies for Security Applications ; : 151-170, 2021.
Article in English | Scopus | ID: covidwho-1353617

ABSTRACT

With Covid-19 creating an unexpected worldwide situation that has brought about changes to the way that people have had to go about their everyday lives, organizations have also had to change their business practices to comply with social distancing guidance, meaning the adoption of remote work solutions where possible. There has also been an observed increase in Cyber attacks, that risk taking advantage of these sudden changes. This paper analyzes the effect of Covid-19 on remote working practices and the Cybersecurity threat landscape. The research has shown an indication that Cybercriminals and Advanced Persistent Threat actors have adapted common attacks such as phishing and teleconferencing vulnerabilities, to take advantage of the confusion and fear surrounding Covid-19. There is a suggestion that the larger or more technically focused organizations within the UK were best prepared and least affected by the move to remote work yet also had a general lack of policies and plans in the event of pandemics and natural disasters that might affect security operations. Based on these observations, it is recommended that organizations collaborate more and aim to explore the possibility of creating regional cyber first responder groups to help organizations in future situations like Covid-19. It can also be recommended that organizations introduce more tailored cyber security awareness training based around threats of remote working. Also to introduce pandemic related policies and plans into business continuity strategies, as standard. This should also contain plans covering who is responsible for what action or roles in an emergency and what to do if security teams are reduced in size. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

9.
IEEE Pervasive Comput ; 20(2): 73-80, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1199621

ABSTRACT

The COVID-19 pandemic has highlighted how the healthcare system could be overwhelmed. Telehealth stands out to be an effective solution, where patients can be monitored remotely without packing hospitals and exposing healthcare givers to the deadly virus. This article presents our Intel award winning solution for diagnosing COVID-19 related symptoms and similar contagious diseases. Our solution realizes an Internet of Things system with multimodal physiological sensing capabilities. The sensor nodes are integrated in a wearable shirt (vest) to enable continuous monitoring in a noninvasive manner; the data are collected and analyzed using advanced machine learning techniques at a gateway for remote access by a healthcare provider. Our system can be used by both patients and quarantined individuals. The article presents an overview of the system and briefly describes some novel techniques for increased resource efficiency and assessment fidelity. Preliminary results are provided and the roadmap for full clinical trials is discussed.

10.
International Journal of Work-Integrated Learning ; 21(5):521-529, 2020.
Article in English | Scopus | ID: covidwho-891186

ABSTRACT

COVID-19 calls for new approaches and frameworks for the delivery of work-integrated learning (WIL). Standalone WIL opportunities are also increasingly difficult to realize, with the current economic climate limiting industry resources available for placements and WIL partnerships. The hybridized WIL model presented in this paper thus proposes the scaffolding of simulated WIL experiences into core undergraduate design curriculum to promote deep, authentic, transformational learning, fostering broader student employability. Noting a gap in design educational research relating to embedded scaffolded WIL, the paper refers to examples of scaffolded WIL experiences across core design studio subjects of a four-year embedded honors interior architecture program. Conceived as a way to prepare students for more significant standalone, cross-disciplinary and cross-national WIL, the authors argue that this model develops the professional skills required by industry and better prepares students to navigate the dynamic real-world problems that societies face, particularly during the pandemic. © 2020 International Journal of Work-Integrated Learning. All rights reserved.

11.
Am J Transplant ; 20(11): 3198-3205, 2020 11.
Article in English | MEDLINE | ID: covidwho-873212

ABSTRACT

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Graft Rejection/prevention & control , Organ Transplantation , SARS-CoV-2 , Transplant Recipients , Aged , Comorbidity , Female , Graft Rejection/epidemiology , Humans , Male , Middle Aged , Pandemics
12.
J Am Soc Nephrol ; 31(9): 1959-1968, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-652873

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series. METHODS: We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had APOL1 high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients. CONCLUSIONS: Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Kidney/pathology , Pneumonia, Viral/pathology , Adult , Aged , Betacoronavirus/isolation & purification , Biopsy , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/immunology , Female , Humans , Kidney/ultrastructure , Kidney/virology , Kidney Diseases/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , SARS-CoV-2
13.
Transpl Infect Dis ; 22(6): e13359, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-617168

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a pandemic since first being described in January 2020. Clinical manifestations in non-transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID-19 infection occurring in pancreas transplant recipients.


Subject(s)
COVID-19/therapy , Kidney Transplantation , Pancreas Transplantation , Telemedicine , Adult , Ambulatory Care , COVID-19/immunology , COVID-19/physiopathology , Deprescriptions , Diabetes Mellitus, Type 1/surgery , Diabetic Nephropathies/surgery , Female , Graft Rejection/prevention & control , Hospitalization , Humans , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Male , Middle Aged , Respiratory Insufficiency/physiopathology , SARS-CoV-2
14.
Am J Transplant ; 20(7): 1800-1808, 2020 07.
Article in English | MEDLINE | ID: covidwho-116890

ABSTRACT

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Organ Transplantation/adverse effects , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Transplant Recipients , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Critical Care , Female , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Intensive Care Units , Intubation , Male , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/mortality , Respiration, Artificial , SARS-CoV-2 , Steroids/therapeutic use , Treatment Outcome , United States , COVID-19 Drug Treatment
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