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1.
Rev. ciênc. farm. básica apl ; 40: [3], 01/01/2019.
Article in English | LILACS (Americas) | ID: covidwho-1106950

ABSTRACT

The use of chloroquine and hydroxychloroquine as off-label treatments for covid-19 disease is a resort for critical care patients under enteral nutrition (EN). However, the use of solid pharmaceutical forms of these drugs through feeding tubes can pose a challenge to the health care team. Therefore, we performed a review of literature regarding administration of chloroquine and hydroxychloroquine through feeding tubes. For this end, a search was performed on PubMed and Lilacs database using key-words and free terms referring to drug administration via feeding tubes, and, specifically chloroquine and hydroxychloroquine. Also, a search on Micromedex® database and on the Handbook of Drug Administration via Enteral Feeding Tubes were performed. A total of 1.784 articles were retrieved. However, 4 articles fitted in the inclusion criteria. Two articles exploring the administration of chloroquine via feeding tubes on children with malaria found no difference on clinical results or tolerability when comparing it with oral or intramuscular administration. Other article showed full dispersion of hydroxychloroquine on water after crushing with mortar and pestle. A review found no information regarding the administration of hydroxychloroquine via postpyloric feeding tubes. No information was found on Micromedex® or the consulted Handbook; however, they pointed out the interaction between chloroquine and multivalent ions if coadministered.(AU)


Subject(s)
Humans , Chloroquine/administration & dosage , Enteral Nutrition/instrumentation , Coronavirus , Hydroxychloroquine/administration & dosage , Coronavirus Infections/therapy
2.
Rev. ciênc. farm. básica apl ; 40: [3], 01/01/2019.
Article in English | LILACS (Americas) | ID: covidwho-1106949

ABSTRACT

The use of chloroquine and hydroxychloroquine as off-label treatments for covid-19 disease is a resort for critical care patients under enteral nutrition (EN). However, the use of solid pharmaceutical forms of these drugs through feeding tubes can pose a challenge to the health care team. Therefore, we performed a review of literature regarding administration of chloroquine and hydroxychloroquine through feeding tubes. For this end, a search was performed on PubMed and Lilacs database using key-words and free terms referring to drug administration via feeding tubes, and, specifically chloroquine and hydroxychloroquine. Also, a search on Micromedex® database and on the Handbook of Drug Administration via Enteral Feeding Tubes were performed. A total of 1.784 articles were retrieved. However, 4 articles fitted in the inclusion criteria. Two articles exploring the administration of chloroquine via feeding tubes on children with malaria found no difference on clinical results or tolerability when comparing it with oral or intramuscular administration. Other article showed full dispersion of hydroxychloroquine on water after crushing with mortar and pestle. A review found no information regarding the administration of hydroxychloroquine via postpyloric feeding tubes. No information was found on Micromedex® or the consulted Handbook; however, they pointed out the interaction between chloroquine and multivalent ions if coadministered.(AU)


Subject(s)
Humans , Chloroquine/administration & dosage , Enteral Nutrition/instrumentation , Coronavirus , Hydroxychloroquine/administration & dosage , Coronavirus Infections/therapy
3.
J Exp Med ; 218(3)2021 03 01.
Article in English | MEDLINE | ID: covidwho-1044017

ABSTRACT

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.


Subject(s)
Antibodies, Monoclonal, Murine-Derived , Antibodies, Neutralizing , Antibodies, Viral , Betacoronavirus/immunology , Coronavirus Infections , Pandemics , Pneumonia, Viral , Animals , Antibodies, Monoclonal, Murine-Derived/immunology , Antibodies, Monoclonal, Murine-Derived/pharmacology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/immunology , Antibodies, Viral/pharmacology , Cell Line , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Female , Humans , Mesocricetus , Mice , Mice, Inbred BALB C , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy
4.
Cell ; 182(4): 828-842.e16, 2020 08 20.
Article in English | MEDLINE | ID: covidwho-1027977

ABSTRACT

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.


Subject(s)
Antibodies, Neutralizing/chemistry , Betacoronavirus/chemistry , Coronavirus Infections/immunology , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin G/chemistry , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/chemistry , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Betacoronavirus/immunology , Coronavirus Infections/blood , Coronavirus Infections/therapy , Cross Reactions , Cryoelectron Microscopy , Epitope Mapping , Epitopes , Humans , Immunization, Passive , Immunoglobulin Fab Fragments/blood , Immunoglobulin Fab Fragments/isolation & purification , Immunoglobulin Fab Fragments/ultrastructure , Immunoglobulin G/blood , Immunoglobulin G/isolation & purification , Immunoglobulin G/ultrastructure , Middle East Respiratory Syndrome Coronavirus/chemistry , Middle East Respiratory Syndrome Coronavirus/immunology , Models, Molecular , Pandemics , Pneumonia, Viral/blood , SARS Virus/chemistry , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology
9.
BMC Med ; 19(1): 19, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1024366

ABSTRACT

BACKGROUND: Cross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission. METHODS: We use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection. RESULTS: We hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model. CONCLUSIONS: This study provides a "proof of possibility" for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.


Subject(s)
Coronavirus Infections , Cross Protection/immunology , Cross Reactions/immunology , /immunology , Age Factors , /immunology , Coronavirus/classification , Coronavirus/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Endemic Diseases , Hospitalization/statistics & numerical data , Humans , Immunity, Heterologous/immunology , Patient-Specific Modeling , Severity of Illness Index
10.
Lung ; 198(5): 771-775, 2020 10.
Article in English | MEDLINE | ID: covidwho-756086

ABSTRACT

PURPOSE: To investigate whether sarcoidosis patients infected with SARS-CoV-2 are at risk for adverse disease outcomes. STUDY DESIGN AND METHODS: This retrospective study was conducted in five hospitals within the Mount Sinai Health System during March 1, 2020 to July 29, 2020. All patients diagnosed with COVID-19 were included in the study. We identified sarcoidosis patients who met diagnostic criteria for sarcoidosis according to accepted guidelines. An adverse disease outcome was defined as the presence of intubation and mechanical ventilation or in-hospital mortality. In sarcoidosis patients, we reported (when available) the results of pulmonary function testing measured within 3 years prior to the time of SARS­CoV­2 infection. A multivariable logistic regression model was used to generate an adjusted odds ratio (aOR) to evaluate sarcoidosis as a risk factor for an adverse outcome. The same model was used to analyze sarcoidosis patients with moderate and/or severe impairment in pulmonary function. RESULTS: The study included 7337 patients, 37 of whom (0.5%) had sarcoidosis. The crude rate of developing an adverse outcome was significantly higher in patients with moderately and/or severely impaired pulmonary function (9/14 vs. 3/23, p = 0.003). While the diagnosis of sarcoidosis was not independently associated with risk of an adverse event, (aOR 1.8, 95% CI 0.9-3.6), the diagnosis of sarcoidosis in patients with moderately and/or severely impaired pulmonary function was associated with an adverse outcome (aOR 7.8, 95% CI 2.4-25.8). CONCLUSION: Moderate or severe impairment in pulmonary function is associated with mortality in sarcoidosis patients infected with SARS­CoV­2.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections , Pandemics , Pneumonia, Viral , Respiratory Function Tests/methods , Sarcoidosis, Pulmonary , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Hospital Mortality , Humans , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , Sarcoidosis, Pulmonary/diagnosis , Sarcoidosis, Pulmonary/epidemiology , Sarcoidosis, Pulmonary/physiopathology , United States/epidemiology
12.
Recenti Prog Med ; 111(4): 212-222, 2020 Apr.
Article in Italian | MEDLINE | ID: covidwho-1024443

ABSTRACT

On 6 March 2020, the Italian Society of Anaesthesia Analgesia Resuscitation and Intensive care (SIAARTI) published the document "Clinical Ethics Recommendations for Admission to and Suspension of Intensive Care in Exceptional Conditions of Imbalance between Needs and Available Resources". The document, which aims to propose treatment decision-making criteria in the face of exceptional imbalances between health needs and available resources, has produced strong reactions, within the medical-scientific community, in the academic world, and in the media. In the current context of international public health emergency caused by the CoViD-19 epidemic, this work aims to explain the ethical, deontological and legal bases of the SIAARTI Document and to propose methodologic and argumentative integrations that are useful for understanding and placing in context the decision-making criteria proposed. The working group that contributed to the drafting of this paper agrees that it is appropriate that healthcare personnel, who is particularly committed to taking care of those who are currently in need of intensive or sub-intensive care, should benefit from clear operational indications that are useful to orient care and, at the same time, that the population should know in advance which criteria will guide the tragic choices that may fall on each one of us. This contribution therefore firstly reflects on the appropriateness of the SIAARTI standpoint and the objectives of the SIAARTI Document. It then turns to demonstrate how the recommendations it proposes can be framed within a shared interdisciplinary, ethical, deontological and legal perspective.


Subject(s)
Coronavirus Infections , Critical Care , Pandemics , Pneumonia, Viral , Resource Allocation/ethics , Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Critical Care/ethics , Critical Care/legislation & jurisprudence , Health Resources , Health Services Needs and Demand , Humans , Intensive Care Units , Interdisciplinary Communication , Italy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Practice Guidelines as Topic , Resource Allocation/legislation & jurisprudence
13.
Recenti Prog Med ; 111(4): 184-185, 2020 04.
Article in Italian | MEDLINE | ID: covidwho-1024442

ABSTRACT

A position statement published by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) is fostering a vibrant debate, crossed by deep fears. These are recommendations addressed to ICU doctors who must decide whether to implement intensive treatments for patients who need them to survive. Specifically, the reference is to the patients to whom the CoViD-19 epidemic has compromised respiratory capacity. We still do not have clear what positive criteria can help make clinical decisions in contexts of insufficient resources that force us to make choices.


Subject(s)
Coronavirus Infections , Decision Making , Health Resources , Pandemics , Pneumonia, Viral , Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/therapy , Decision Making/ethics , Health Resources/supply & distribution , Hospitals, Group Practice , Humans , Informed Consent , Patient Rights , Physicians , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Severity of Illness Index
14.
Emerg Med J ; 37(9): 572-575, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1024251

ABSTRACT

The COVID-19 pandemic has led to a surge of information being presented to clinicians regarding this novel and deadly disease. There is a clear urgency to collate, review, appraise and act on this information if we are to do the best for clinicians and patients. However, the speed of the pandemic is a threat to traditional models of knowledge translation and practice change. In this concepts paper, we argue that clinicians need to be agile in their thinking and practice in order to find the right time to change. Adoption of new methods should be based on clinical judgement, the weight of evidence and the balance of probabilities that any new technique, test or treatment might work. The pandemic requires all of us to reach a new level of evidence-based medicine characterised by scepticism, thoughtfulness, responsiveness and clinically agility in practice.


Subject(s)
Coronavirus Infections , Critical Pathways , Evidence-Based Medicine , Pandemics , Pneumonia, Viral , Translational Medical Research , Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Critical Pathways/organization & administration , Critical Pathways/trends , Evidence-Based Medicine/education , Evidence-Based Medicine/methods , Evidence-Based Medicine/organization & administration , Humans , Knowledge Management , Organizational Innovation , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Quality Improvement , Surge Capacity , Translational Medical Research/education , Translational Medical Research/trends
15.
Emerg Med J ; 37(9): 565-566, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1024248

ABSTRACT

We report the experience of prone ventilation in selected patients treated with helmet non-invasive ventilation (NIV) continuous positive airway pressure (CPAP) for acute respiratory failure in COVID-19 pneumonia. Preliminary results showed an improvement in the PaO2 value and PaO2/FiO2 ratio after 1 hour of prone ventilation. No variation of the lung ultrasound pattern before and after prone ventilation has been detected. At the time of writing, we attempted proning with helmet NIV CPAP in 10 patients. In 4 out of 10 patients, the attempt failed due to lack of compliance of the patient, scarce pain control even with ongoing treatment and refusal by the patient to prone positioning.


Subject(s)
Continuous Positive Airway Pressure/methods , Coronavirus Infections , Noninvasive Ventilation/methods , Pandemics , Pneumonia, Viral , Prone Position , Respiratory Insufficiency , Aged , Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Italy/epidemiology , Male , Oxygen Consumption , Oxygen Inhalation Therapy/methods , Patient Positioning , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Treatment Outcome
16.
J Occup Environ Med ; 62(11): 898-903, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1024146

ABSTRACT

OBJECTIVES: To explore the level and influencing factors of help-seeking behavior of returning to work in healthcare workers (HCWs). METHODS: A total of 861 HCWs were surveyed. A structured self-administered questionnaire was used to collect data. Multivariable logistic regression was performed to examine the influencing factors of help-seeking behavior. RESULTS: HCWs sought help with respect to COVID-19-diagnosized problem most. Help-seeking intention, problems encountered after return, test for return, work condition during COVID-19, relatives or friends diagnosed or suspected as COVID-19, and socio-demographic characteristics such as occupation, education, title, and marriage status are predictors of help-seeking behavior. CONCLUSIONS: Education and intervention should lay particular stress on HCWs featured rest at home before return, doctor, lower education and lower title to ensure the safety, accuracy, and quality of work after they return to work for a better occupational environment.


Subject(s)
Betacoronavirus , Coronavirus Infections/psychology , Health Personnel/psychology , Help-Seeking Behavior , Pneumonia, Viral/psychology , Return to Work/psychology , Adult , China , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Female , Humans , Intention , Logistic Models , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Socioeconomic Factors , Surveys and Questionnaires
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