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1.
Rev Med Suisse ; 16(698): 1262-1264, 2020 Jun 17.
Artículo en Francés | MEDLINE | ID: mdl-32558456

RESUMEN

The current new coronavirus pandemic has highlighted the importance of taking into consideration population groups particularly at risk of contracting Covid-19 disease or developing severe forms of the disease. The medical literature, the press and the authorities have thus stepped up the use of the expression «â€…vulnerable populations ¼ in recent weeks to refer to it. However, behind this general expression there are diverse but often interdependent realities whose specific consideration and understanding seem essential for the effective management of the epidemic and its health and socio-economic consequences.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Poblaciones Vulnerables/estadística & datos numéricos , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/economía , Humanos , Pandemias/economía , Neumonía Viral/economía
2.
Trials ; 21(1): 468, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493441

RESUMEN

OBJECTIVES: The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6, IL-6 receptor and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome. TRIAL DESIGN: A phase 3 prospective, multi-center, interventional, open label, 6-arm 2x2 factorial design study. PARTICIPANTS: Subjects will be recruited at the specialized COVID-19 wards and/or ICUs at 16 Belgian participating hospitals. Only adult (≥18y old) patients will be recruited with recent (≤16 days) COVID-19 infection and acute hypoxia (defined as PaO2/FiO2 below 350mmHg or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation) and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those, who have not been on mechanical ventilation for more than 24 hours before randomisation. Patients should have had a chest X-ray and/or CT scan showing bilateral infiltrates within the last 2 days before randomisation. Patients with active bacterial or fungal infection will be excluded. INTERVENTION AND COMPARATOR: Patients will be randomized to 1 of 5 experimental arms versus usual care. The experimental arms consist of Anakinra alone (anti-IL-1 binding the IL-1 receptor), Siltuximab alone (anti-IL-6 chimeric antibody), a combination of Siltuximab and Anakinra, Tocilizumab alone (humanised anti-IL-6 receptor antibody) or a combination of Anakinra with Tocilizumab in addition to standard care. Patients treated with Anakinra will receive a daily subcutaneous injection of 100mg for a maximum of 28 days or until hospital discharge, whichever comes first. Siltuximab (11mg/kg) or Tocilizumab (8mg/kg, with a maximum dose of 800mg) are administered as a single intravenous injection immediately after randomization. MAIN OUTCOMES: The primary end point is the time to clinical improvement defined as the time from randomization to either an improvement of two points on a six-category ordinal scale measured daily till day 28 or discharge from the hospital or death. This ordinal scale is composed of (1) Death; (2) Hospitalized, on invasive mechanical ventilation or ECMO; (3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, not requiring supplemental oxygen; (6) Not hospitalized. RANDOMISATION: Patients will be randomized using an Interactive Web Response System (REDCap). A 2x2 factorial design was selected with a 2:1 randomization regarding the IL-1 blockade (Anakinra) and a 1:2 randomization regarding the IL-6 blockade (Siltuximab and Tocilizumab). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 342 participants will be enrolled: 76 patients will receive usual care, 76 patients will receive Siltuximab alone, 76 patients will receive Tocilizumab alone, 38 will receive Anakinra alone, 38 patients will receive Anakinra and Siltuximab and 38 patients will receive Anakinra and Tocilizumab. TRIAL STATUS: COV-AID protocol version 3.0 (15 Apr 2020). Participant recruitment is ongoing and started on April 4th 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 1st, 2020 (ClinicalTrials.gov Identifier: NCT04330638) and on EudraCT on April 3rd 2020 (Identifier: 2020-001500-41). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Bélgica , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Ensayos Clínicos Fase III como Asunto , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Quimioterapia Combinada , Interacciones Huésped-Patógeno , Humanos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Interleucina-1/antagonistas & inhibidores , Interleucina-1/sangre , Interleucina-1/inmunología , Interleucina-6/antagonistas & inhibidores , Interleucina-6/sangre , Interleucina-6/inmunología , Estudios Multicéntricos como Asunto , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Neumonía Viral/virología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Interleucina-6/antagonistas & inhibidores , Receptores de Interleucina-6/sangre , Receptores de Interleucina-6/inmunología , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
3.
BMC Med Res Methodol ; 20(1): 146, 2020 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-32505172

RESUMEN

BACKGROUND: Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA. METHODS: We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test. RESULTS: Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. CONCLUSION: The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.


Asunto(s)
Teorema de Bayes , Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Pandemias , Neumonía Viral , Alberta/epidemiología , Betacoronavirus/patogenicidad , Sesgo , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Humanos , Philadelphia/epidemiología , Sensibilidad y Especificidad , Incertidumbre
4.
Vaccine ; 38(31): 4783-4791, 2020 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-32507409

RESUMEN

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of "disease enhancement" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.


Asunto(s)
Anticuerpos Antivirales/efectos adversos , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Neumonía Viral/inmunología , Vacunas Virales/efectos adversos , Vacunas Virales/inmunología , Animales , Betacoronavirus/patogenicidad , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Modelos Animales de Enfermedad , Humanos , Pandemias , Neumonía Viral/virología , Medición de Riesgo , Síndrome Respiratorio Agudo Grave/inmunología
5.
J Exp Clin Cancer Res ; 39(1): 109, 2020 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-32522223

RESUMEN

If we focus our attention on seven main features of COVID-19 infection (heterogeneity, fragility, lack of effective treatments and vaccines, "miraculous cures", psychological suffering, deprivation, and globalization), we may establish parallelism with the challenges faced in the steep road to the understanding and treatment of neoplastic diseases. How the similarities between these two conditions can help us cope with the emergency effort represented by the management of cancer patients in the COVID-19 era, today and in the future? In a manner similar to the Cancer Moonshot initiative in the United States, we can hypothesize a multinational moonshot project towards the management of cancer patients during COVID-19 pandemic. In particular, we believe that the main road to elaborate meaningful scientific evidence is represented by the collection of all the data on COVID-19 and cancer comorbidity that are and will become available in cancer centers, coupled with the design of large clinical studies. To address this goal, it is essential to identify the entity that can produce this scientific evidences and the potentially most successful research strategy to undertake. The largest Italian organization for cancer research, Alliance Against Cancer (Alleanza Contro il Cancro, ACC), is called to play a scientific leadership in addressing these challenges, which requires the coordination of oncology teams at regional, national, and international levels. To fulfill this commitment, ACC will create a liaison with health government agencies in order to develop "dynamic" indications able to fight such an unpredictable pandemic.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Oncología Médica/tendencias , Neoplasias/epidemiología , Pandemias , Neumonía Viral/epidemiología , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/patología , Agencias Gubernamentales , Humanos , Italia/epidemiología , Neoplasias/complicaciones , Neoplasias/patología , Neoplasias/terapia , Neumonía Viral/complicaciones , Neumonía Viral/patología
7.
Infez Med ; 28(suppl 1): 6-17, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32532933

RESUMEN

Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world. To date, seven known strains of HCoVs belonging to four genera (i.e., α?, ß?, γ, and δ-CoV) have been recognized; the latest one has been identified as the SARS-CoV-2. Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body. Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19. Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19. There is a greater need to better understand the mechanisms and risk factors of transmission routes. To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear. Therefore, there is an urgent need for update data on SARS-CoV-2. Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020.


Asunto(s)
Betacoronavirus/patogenicidad , Enfermedades Transmisibles Emergentes/epidemiología , Infecciones por Coronavirus/epidemiología , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Neumonía Viral/epidemiología , Virus del SRAS/patogenicidad , Síndrome Respiratorio Agudo Grave/epidemiología , Factores de Edad , Animales , Animales Salvajes/virología , Betacoronavirus/aislamiento & purificación , China , Enfermedades Transmisibles Emergentes/transmisión , Enfermedades Transmisibles Emergentes/virología , Comorbilidad , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/transmisión , Susceptibilidad a Enfermedades , Transmisión de Enfermedad Infecciosa , Femenino , Geografía Médica , Salud Global , Especificidad del Huésped , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Pandemias , Neumonía Viral/virología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Síndrome de Dificultad Respiratoria del Adulto/etiología , Síndrome de Dificultad Respiratoria del Adulto/mortalidad , Factores de Riesgo , Virus del SRAS/aislamiento & purificación , Síndrome Respiratorio Agudo Grave/transmisión , Síndrome Respiratorio Agudo Grave/virología , Factores Sexuales , Zoonosis
8.
Ars pharm ; 61(2): 63-79, abr.-jun. 2020. tab, ilus, graf
Artículo en Español | IBECS | ID: ibc-188101

RESUMEN

INTRODUCCIÓN: En diciembre de 2019, se detectaron los primeros casos de enfermedad respiratoria causada por un coronavirus emergente, al que se denominó SARS-CoV-2, que en los primeros meses de 2020 se ha extendido por todo el mundo con características de pandemia. MÉTODO: Se examinaron las publicaciones más relevantes en relación con los objetivos de la revisión. RESULTADOS: La enfermedad, conocida como COVID-19, cursa con tos, fiebre y dificultad respiratoria. Las formas más graves, que afectan principalmente a personas de edad avanzada y con determinadas comorbilidades, se manifiestan por afectación de la función respiratoria, que requiere ventilación mecánica, y síndrome de respuesta inflamatoria sistémica, que puede conducir a un choque séptico con fallo multiorgánico, y altas tasas de mortalidad. En esta revisión se examina el estado actual de conocimientos sobre las características y origen del SARS-CoV-2, su replicación, y la patogénesis, clínica, diagnóstico, tratamiento y prevención de COVID-19. CONCLUSIONES: Las características del SARS-CoV-2 y la clínica de COVID-19 son bien conocidas. La PCR es la técnica de referencia para el diagnóstico de laboratorio; se dispone de ensayos para detección de antígenos y de anticuerpos, con margen de optimización. Los protocolos de tratamiento incluyen la corrección de la respuesta inflamatoria sistémica y administración de agentes antivirales. Existen vacunas en desarrollo


INTRODUCTION: In December 2019, the first cases of respiratory disease caused by an emerging coronavirus were detected. The causative agento f the outbreak was called SARS-CoV-2, and in the first months of 2020 it spread throughout the world as a pandemic. METHOD: The most relevant publications concerned with the aims of the review were examined. RESULTS: The disease, known as COVID-19. Patients show cough, fever, and respiratory distress. The most severe forms, mainly affecting the elderly and associated with various comorbidities, are manifested by impaired respiratory function, requiring mechanical ventilation, and systemic inflammatory response syndrome, which can lead to septic shock with multi-organ failure and high mortality rates. This review examines the current state of knowledge about the characteristics and origin of SARS-CoV-2, its replication, and the pathogenesis, clinical, diagnosis, treatment, and prevention of COVID-19. CONCLUSIONS: The characteristics of SARS-CoV-2 and the clinical manifestations of COVID-19 are well known. PCR is the reference technique for laboratory diagnosis; assays for the detection of antigens and antibodies are available, with optimization possibilities. Treatment protocols include attenuation of the systemic inflammatory response and administration of antiviral agents. There are vaccines in development


Asunto(s)
Humanos , Infecciones por Coronavirus , Neumonía Viral , Betacoronavirus/patogenicidad , Pandemias , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Neumonía Viral/terapia
9.
Fertil Steril ; 113(6): 1140-1149, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32482250

RESUMEN

OBJECTIVE: To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. DESIGN: Review of English publications in PubMed and Embase to April 6, 2020. METHOD(S): Articles were screened for reports including coronavirus, reproduction, pathophysiology, and pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Reproductive outcomes, effects on gametes, pregnancy outcomes, and neonatal complications. RESULT(S): Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin-converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following Coronavirus Disease 2019 (COVID-19) infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-Coronavirus 2 (CoV-2) adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or Middle East respiratory syndrome (MERS), but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. Coronavirus Disease 2019 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. CONCLUSION(S): Coronavirus Disease 2019 infection may affect adversely some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/virología , Infertilidad Femenina/virología , Infertilidad Masculina/virología , Orquitis/virología , Neumonía Viral/virología , Reproducción , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Femenino , Fertilidad , Interacciones Huésped-Patógeno , Humanos , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/fisiopatología , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/fisiopatología , Masculino , Orquitis/diagnóstico , Orquitis/fisiopatología , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Embarazo , Complicaciones Infecciosas del Embarazo/fisiopatología , Complicaciones Infecciosas del Embarazo/virología , Resultado del Embarazo , Medición de Riesgo , Factores de Riesgo , Recuento de Espermatozoides , Motilidad Espermática
10.
Trials ; 21(1): 474, 2020 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-32493459

RESUMEN

OBJECTIVES: Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS. HYPOTHESIS: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties. TRIAL DESIGN: Pilot, parallel design randomised controlled trial. PARTICIPANTS: The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia. INTERVENTION AND COMPARATOR: Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose - 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed. Comparator: Standard supportive care. MAIN OUTCOMES: Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale. RANDOMISATION: Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes. BLINDING (MASKING): This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Twelve participants in each group. Total n=24. TRIAL STATUS: CBC-19 protocol v2, dated 23rd April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July - 31st December 2020. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Betacoronavirus/patogenicidad , Trasplante de Células Madre de Sangre del Cordón Umbilical , Infecciones por Coronavirus/cirugía , Neumonía Viral/cirugía , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Progresión de la Enfermedad , Interacciones Huésped-Patógeno , Humanos , Pandemias , Proyectos Piloto , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Resultado del Tratamiento , Victoria
11.
Trials ; 21(1): 469, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493460

RESUMEN

OBJECTIVES: Entertainment-education (E-E) media can improve behavioral intent toward health-related practices. In the era of COVID-19, millions of people can be reached by E-E media without requiring any physical contact. We have designed a short, wordless, animated video about COVID-19 hygiene practices-such as social distancing and frequent hand washing-that can be rapidly distributed through social media channels to a global audience. The E-E video's effectiveness, however, remains unclear. The study aims to achieve the following objectives. To: 1.Quantify people's interest in watching a short, animated video about COVID-19 hygiene (abbreviated to CoVideo).2.Establish the CoVideo's effectiveness in increasing behavioural intent toward COVID-19 hygiene.3.Establish the CoVideo's effectiveness in improving COVID-19 hygiene knowledge. TRIAL DESIGN: The present study is a multi-site, parallel group, randomized controlled trial (RCT) comparing the effectiveness of the CoVideo against an attention placebo control (APC) video or no video. The trial has an intervention arm (CoVideo), placebo arm (APC), and control arm (no video). Nested in each trial arm is a list experiment and questionnaire survey, with the following ordering. Arm 1: the CoVideo, list experiment, and questionnaire survey. Arm 2: the APC video, list experiment, questionnaire survey, and CoVideo. Arm 3: the list experiment, questionnaire survey, and CoVideo. For each list experiment, participants will be randomized to a control or treatment group. The control group will receive a list of five items and the treatment group will receive the same five items plus one item about COVID-19 hygiene. We will use the list experiment to reduce response bias associated with socially desirable answers to COVID-19 questions. The questionnaire survey will include items about the participant's age, sex, country of residence, highest education, and knowledge of COVID-19 spread. After completing the list experiment and questionnaire survey, participants in Arms 2 and 3 will receive the CoVideo to ensure post-trial access to treatment. PARTICIPANTS: This will be an online study setting. We will use Prolific Academic (ProA: https://www.prolific.co) to recruit participants and host our study on the Gorilla™ platform (www.gorilla.sc). To be eligible, participants must be between the age of 18 and 59 years (male, female, or other) and have current residence in the United States, the United Kingdom, Germany, Spain, Mexico, or France. Participants will be excluded from the study if they cannot speak English, German, French, or Spanish (since the instructions and survey questions will be available in these 4 languages only). INTERVENTION AND COMPARATOR: The intervention is an E-E video about COVID-19 hygiene (CoVideo). Developed by our co-author (MA) for Stanford Medicine, the CoVideo is animated with sound effects, and has no words, speech, or text. The CoVideo shows how the novel coronavirus is spread (airborne, physical contact) and summarizes the public's response to the COVID-19 outbreak. Key components of the CoVideo are the promotion of five hygiene practices: i) social distancing and avoiding group gatherings, ii) frequently washing hands with soap and water or sanitizer, iii) cleaning surfaces at home (e.g., kitchen counters), iv) not sharing eating utensils, and v) avoidance of stockpiling essential goods (such as toilet paper and face masks). The CoVideo, which was designed for universal reach and optimized for release on social media channels, can be viewed at https://www.youtube.com/watch?v=rAj38E7vrS8. The comparators are an APC video (Arm 2) or no video (Arm 3). The APC video is similar in style to the CoVideo; it is also animated with a duration of 2.30 minutes, has sound effects but no words, speech, or text. The video message is about how small choices become actions, which become habits, which become a way of life. It is available at https://www.youtube.com/watch?v=_HEnohs6yYw. Each list experiment will have a control list as the comparator. The control list is needed to measure the prevalence of behavioral intent toward COVID-19 hygiene. MAIN OUTCOMES: This study will measure primary and secondary outcomes related to COVID-19 hygiene. By hygiene, we mean the adoption of behaviors or practices that reduce the chances of being infected or spreading COVID-19. As our primary outcome, we will measure changes in behavioral intent toward five hygiene practices: social distancing, washing hands, cleaning household surfaces, not sharing eating utensils, and not stockpiling essential goods. As a secondary outcome, we will measure knowledge about behaviors that can prevent the spread of COVID-19. RANDOMIZATION: Using a web-based randomization algorithm, Gorilla will randomly allocate participants to the intervention (CoVideo), placebo (APC), or control (no video) arm (sequence generation) at a 1:1:1 ratio. Within each trial arm, Gorilla will randomly allocate participants at a 1:1 ratio to the control or treatment group. Items in the lists will be randomly ordered to avoid order effects. The presentation order of the list experiments will also be randomized. BLINDING: Because ProA handles the interaction between the study investigators and participants, the participants will be completely anonymous to the study investigators. The outcome measures will be self-reported and submitted anonymously. All persons in the study team will be blinded to the group allocation. NUMBERS TO BE RANDOMIZED: The Gorilla algorithm will randomize 6,700 participants to each trial arm, giving a total sample size of 20,100. TRIAL STATUS: The protocol version number is 1.0 and the date is 18 May 2020. Recruitment is expected to end by 22 June 2020. Thus far, the study investigators have recruited 2,500 participants on ProA. Of these participants, 800 have completed the study on the Gorilla platform. TRIAL REGISTRATION: The study and its outcomes were registered at the German Clinical Trials Register (www.drks.de) on May 12th, 2020, protocol number: #DRKS00021582. The study was registered before any data was collected. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/prevención & control , Desinfección de las Manos , Conductas Relacionadas con la Salud , Educación en Salud/métodos , Conocimientos, Actitudes y Práctica en Salud , Pandemias/prevención & control , Neumonía Viral/prevención & control , Opinión Pública , Grabación en Video , Adolescente , Adulto , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Europa (Continente) , Femenino , Comunicación en Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Neumonía Viral/transmisión , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Estados Unidos , Adulto Joven
12.
Trials ; 21(1): 473, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493468

RESUMEN

OBJECTIVES: We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill. TRIAL DESIGN: This is a single center, open label, randomized, controlled, parallel group, clinical trial that will be conducted at Loghman Hakim Medical Education Center in conjunction with Shahid Beheshti University of Medical Sciences. PARTICIPANTS: Sixty COVID-19 confirmed cases (using the RT-PCR test) will be enrolled in the trial between April 9th to April 14th 2020. Patients will be randomly assigned to the intervention groups or the control group with the following eligibility criteria: ≥ 18 years of age AND (oxygen saturation (SPO2) ≤ 93% OR respiratory rate ≥ 24) AND at least one of the following: Contactless infrared forehead thermometer temperature of ≥37.8, cough, sputum production, nasal discharge, myalgia, headache or fatigue on admission, and time of onset of the symptoms should be acute (Days ≤ 14). Although Hydroxychloroquine will be administered in a single dose, patients with heart problems (prolonged QT or PR intervals, second- or third-degree heart block, and arrhythmias including torsade de pointes) will be excluded. Other exclusion criteria include using drugs with potential interaction with Hydroxychloroquine + Lopinavir/Ritonavir, Interferon-ß 1a, Interferon-ß 1b, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results and refusal to participate. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services. INTERVENTION AND COMPARATOR: COVID-19 confirmed patients will be randomly assigned to one of three groups, with 20 patients in each. The first group (Arm 1) will receive Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-ß 1a (Recigen), the second group (Arm 2) will be administered Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-ß 1b (Ziferon), and the control group (Arm 3) will be treated by Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra). MAIN OUTCOMES: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes include mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. If any patient dies, we have reached an important secondary outcome. SpO2 Improvement between the last and first day of hospitalization, using pulse-oximetry. Duration of hospitalization from date of randomization until the date of hospital discharge or date of death from any cause, whichever comes first. Incidence of new mechanical ventilation uses from date of randomization until the last day of the study. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. Statistical analysis will be performed by R version 3.6.1 software. We will use Kaplan-Meier to analyze the time to clinical improvement (compared with a log-rank test). Hazard ratios with 95% confidence intervals will be calculated using the Cox proportional-hazards model in crude and adjusted analysis. RANDOMIZATION: Eligible patients will be randomly assigned in a 1:1:1 ratio to receive either Interferon Beta 1a, Interferon Beta 1b or standard care only. Patients will be randomly allocated to three therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Of the 60 patients who underwent randomization, 20 patients were assigned to receive Interferon beta-1a, 20 patients were assigned to receive Interferon beta 1b plus standard care and the rest of patients were assigned to receive the standard care alone. TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on 9th April 2020 and the end date was on 14th April 2020. Last point of data collection will be the last day on which all of the 60 participants have had an outcome of clinical improvement or death, completing the study's follow-up time window. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04343768, registered April 8, 2020 and first available online April 13, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Interferón beta-1a/uso terapéutico , Interferon beta-1b/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Antivirales/efectos adversos , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Combinación de Medicamentos , Quimioterapia Combinada , Interacciones Huésped-Patógeno , Humanos , Hidroxicloroquina/uso terapéutico , Interferón beta-1a/efectos adversos , Interferon beta-1b/efectos adversos , Irán , Lopinavir/uso terapéutico , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/uso terapéutico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
13.
Trials ; 21(1): 466, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493475

RESUMEN

OBJECTIVES: Primary objective: to evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Secondary objectives: To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of asymptomatic SARS-CoV-2 infection.To evaluate the efficacy of melatonin to prevent the development of severe COVID-19 in the participants enrolled in this study who develop SARS-CoV-2 infection along the trial.To evaluate the duration of COVID-19 symptoms in participants receiving melatonin before the infection.To evaluate seroconversion timing post-symptom onset. Exploratory objectives:To compare severity of COVID-19 between men and women.To evaluate the influence of sleep and diet on prevention from SARS-CoV-2 infection.To evaluate the effect of melatonin on the incidence and characteristics of lymphopenia and increase of inflammatory cytokines related to COVID-19. TRIAL DESIGN: This is a two-arm parallel randomised double-blind controlled trial to evaluate the efficacy of melatonin versus placebo in the prophylaxis of coronavirus disease 2019 among healthcare workers. PARTICIPANTS: Inclusion Criteria: Male or female participants ≥ 18 and ≤ 80 years of age.Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection.Not having a previous COVID19 diagnosis.Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1st 2020 until study enrolment.Having a negative SARS-CoV 2 reverse-transcription PCR (RT-PCR) result or a negative serologic rapid test (IgM/IgG) result before randomization.Premenopausal women must have a negative urinary pregnancy test in the 7 days before starting the trial treatment.Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method. EXCLUSION CRITERIA: HIV infection.Active hepatitis B infection.Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis.Osteoporosis.Myasthenia gravis.Pre-existent maculopathy.Retinitis pigmentosa.Bradycardia (less than 50 bpm).Weight less than 40 Kg.Participant with any immunosuppressive condition or hematological disease.Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone.Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption.Treatment with fluvoxamine.Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon.Pregnancy.Breastfeeding.History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis.Insulin-dependent diabetes mellitus.Known history of hypersensitivity to the study drug or any of its components.Patients that should not be included in the study at the judgment of the research team. Participants will be recruited from the following eight hospitals in Madrid, Spain: Hospital Universitario La Paz, Hospital Ramón y Cajal, Hospital Infanta Sofía, Hospital 12 de Octubre, Hospital Clínico San Carlos, Hospital Central de la defensa Gómez Ulla,Hospital de La Princesa and Hospital Infanta Leonor. INTERVENTION AND COMPARATOR: Experimental: Melatonin (Circadin®, Exeltis Healthcare, Spain): 2 mg of melatonin orally before bedtime for 12 weeks. Comparator: Identical looking placebo (Laboratorios Liconsa, Spain) orally before bedtime for 12 weeks. MAIN OUTCOMES: Number of SARS-CoV-2 (COVID-19) symptomatic infections confirmed by polymerase chain reaction (PCR) test or serologic test or according to each centre diagnosis protocol. Primary outcome will be measured until the end of treatment for each participant (until the date of the last dose taken by each patient). RANDOMISATION: Patients who meet all inclusion and no exclusion criteria will be randomised, stratified by centres, sex and age (<50 and ≥ 50 years old). The randomisation sequence was created using SAS version 9.4 statistical software (procedure 'PROC PLAN') with a 1:1 allocation. No randomisation seed was specified. The randomisation seed was generated taking the hour of the computer where the program was executed. Randomization will be done centrally through the electronic system RedCAP® in order to conceal the sequence until interventions are assigned BLINDING (MASKING): Participants, caregivers, and those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 450 participants are planned to be enrolled in this clinical trial, 225 in the experimental arm and 225 in the placebo arm. TRIAL STATUS: Protocol version 3.0, 17th of April 2020. Recruitment ongoing. First participant was recruited on the 21st of April 2020. The final participant is anticipated to be recruited on the 31st of May 2020. As of May 18th, 2020, a total of 312 participants have been enrolled (154 at Hospital La Paz, 85 at Hospital Infanta Sofía and 73 at Hospital 12 de Octubre). TRIAL REGISTRATION: EU Clinical Trials Register: 2020-001530-35; Date of trial registration: 13th of April 2020; https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001530-35/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Melatonina/administración & dosificación , Exposición Profesional/efectos adversos , Salud Laboral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Antivirales/efectos adversos , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Quimioprevención , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Método Doble Ciego , Femenino , Humanos , Masculino , Melatonina/efectos adversos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Seroconversión , España , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
14.
Trials ; 21(1): 475, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493478

RESUMEN

OBJECTIVES: Primary Objective • To test the efficacy of Hydroxychloroquine (HCQ) (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection Secondary objectives • To determine the safety and tolerability of HCQ as SARS-CoV-2 Post-exposure Prophylaxis (PEP) in adults • To test the efficacy of HCQ (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection 2 weeks after completing therapy, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection • To test the efficacy of HCQ to shorten the duration of SARS-CoV-2 shedding among those with SARS-CoV-2 infection in the HCQ PEP group • To test the efficacy of HCQ to prevent incident COVID-19 TRIAL DESIGN: This is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of HCQ PEP for the prevention of SARS-CoV-2 infection in adults exposed to the virus. PARTICIPANTS: This study will enroll up to 2000 asymptomatic adults 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test. This multisite trial will be conducted at seven sites in Seattle (UW), Los Angeles (UCLA), New Orleans (Tulane), Baltimore (UMB), New York City (NYU), Syracuse (SUNY-Upstate), and Boston (BMC). Inclusion criteria Participants are eligible to be included in the study only if all of the following criteria apply: 1.Men or women 18 to 80 years of age inclusive, at the time of signing the informed consent2.Willing and able to provide informed consent3.Had a close contact of a person (index) with known PCR-confirmed SARS-CoV-2 infection or index who is currently being assessed for COVID-19 Close contact is defined as: a.Household contact (i.e., residing with the index case in the 14 days prior to index diagnosis or prolonged exposure within a residence/vehicle/enclosed space without maintaining social distance)b.Medical staff, first responders, or other care persons who cared for the index case without personal protection (mask and gloves)4.Less than 4 days since last exposure (close contact with a person with SARS-CoV-2 infection) to the index case5.Access to device and internet for Telehealth visits6.Not planning to take HCQ in addition to the study medication Exclusion criteria Participants are excluded from the study if any of the following criteria apply: 1.Known hypersensitivity to HCQ or other 4-aminoquinoline compounds2.Currently hospitalized3.Symptomatic with subjective fever, cough, or shortness of breath4.Current medications exclude concomitant use of HCQ5.Concomitant use of other anti-malarial treatment or chemoprophylaxis, including chloroquine, mefloquine, artemether, or lumefantrine.6.History of retinopathy of any etiology7.Psoriasis8.Porphyria9.Known bone marrow disorders with significant neutropenia (polymorphonuclear leukocytes <1500) or thrombocytopenia (<100 K)10.Concomitant use of digoxin, cyclosporin, cimetidine, amiodarone, or tamoxifen11.Known moderate or severe liver disease12.Known long QT syndrome13.Severe renal impairment14.Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of the study drugs or planned use during the study period INTERVENTION AND COMPARATOR: Households will be randomized 1:1 (at the level of household), with close contact participants receiving one of the following therapies: •HCQ 400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days •Placebo-like control (ascorbic acid) 500 mg orally daily for 3 days then 250 mg orally daily for 11 days MAIN OUTCOMES: The primary outcome of the study is the incidence of SARS-CoV-2 infection through day 14 among participants who are SARS-CoV-2 negative at baseline by randomization group. RANDOMISATION: Participants will be randomized in a 1:1 ratio to HCQ or ascorbic acid at the level of the household (all eligible participants in 1 household will receive the same intervention). The randomization code and resulting allocation list will be generated and maintained by the Study Statistician. The list will be blocked and stratified by site and contact type (household versus healthcare worker). BLINDING (MASKING): This is a blinded study. HCQ and ascorbic acid will appear similar, and taste will be partially masked as HCQ can be bitter and ascorbic acid will be sour. The participants will be blinded to their randomization group once assigned. Study team members, apart from the Study Pharmacist and the unblinded statistical staff, will be blinded. Laboratory staff are blinded to the group allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size for the study is N=2 000 participants randomized 1:1 to either HCZ (n=1 000) and ascorbic acid (n=1 000). TRIAL STATUS: Protocol version: 1.2 05 April 2020 Recruitment is ongoing, started March 31 and anticipated end date is September 30, 2020. TRIAL REGISTRATION: ClinicalTrials.gov, Protocol Registry Number: NCT04328961 Date of registration: April 1, 2020, retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Hidroxicloroquina/administración & dosificación , Exposición Profesional/efectos adversos , Profilaxis Posexposición , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/efectos adversos , Ácido Ascórbico/administración & dosificación , Betacoronavirus/patogenicidad , Trazado de Contacto , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Esquema de Medicación , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Salud Laboral , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Esparcimiento de Virus/efectos de los fármacos , Adulto Joven
15.
Trials ; 21(1): 472, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493494

RESUMEN

BACKGROUND: SARS-CoV-2 infection presents a high transmission in the group of health professionals in Spain (12-15% infected). Currently there is no accepted chemoprophylaxis but hydroxychloroquine (HDQ) is known to inhibit the coronavirus in vitro. Our hypothesis is that oral administration of hydroxychloroquine to healthcare professionals can reduce the incidence and prevalence of infection as well as its severity in this group. METHODS: Design: Prospective, single center, double blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult health-care professionals (18-65 years) working in areas of high exposure and high risk of transmission of SARS-COV-2 (COVID areas, Intensive Care Unit -ICUs-, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Exclusion criteria include previous infection with SARS CoV2 (positive SARS-CoV-2 PCR or IgG serology), pregnancy or lactation, any contraindication to hydroxychloroquine or evidence of unstable or clinically significant systemic disease. INTERVENTIONS: Patients will be randomized (1:1) to receive once-daily oral Hydroxychloroquine 200mg for two months (HC group) or placebo (P group) in addition to the protective measures appropriate to the level of exposure established by the hospital. A serological evaluation will be carried out every 15 days with PCR in case of seroconversion, symptoms or risk exposure. Primary outcome is the percentage of subjects presenting infection (seroconversion and/or PCR +ve) by the SARS-Cov-2 virus during the observation period. Additionally, both the percentage of subjects in each group presenting Pneumonia with severity criteria (Curb 65 ≥2) and that of subjects requiring admission to ICU will be determined. DISCUSSION: While awaiting a vaccine, hygiene measures, social distancing and personal protective equipment are the only primary prophylaxis measures against SARS-CoV-2, but they have not been sufficient to protect our healthcare professionals. Some evidence of the in vitro efficacy of hydroxychloroquine against this virus is known, along with some clinical data that would support the study of this drug in the chemoprophylaxis of infection. However, there are still no data from controlled clinical trials in this regard. If our hypothesis is confirmed, hydroxychloroquine can help professionals fight this infection with more guarantees. PARTICIPANTS: This is a single-center study that will be carried out at the Marqués de Valdecilla University Hospital. 450 health professionals working at the Hospital Universitario Marqués de Valdecilla in areas of high exposure and high risk of transmission of SARS COV2 (COVID hospital areas, Intensive Care Unit, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. INCLUSION CRITERIA: 1) Health professionals aged between 18 and 65 years (inclusive) at the time of the first screening visit; 2) They must provide signed written informed consent and agree to comply with the study protocol; 3) Active work in high exposure areas during the last two weeks and during the following weeks. EXCLUSION CRITERIA: 1) Previous infection with SARS CoV2 (positive coronavirus PCR or positive serology with SARS Cov2 negative PCR and absence of symptoms); 2) Current treatment with hydroxychloroquine or chloroquine; 3) Hypersensitivity, allergy or any contraindication for taking hydroxychloroquine, in the technical sheet; 4) Previous or current treatment with tamoxifen or raloxifene; 5) Previous eye disease, especially maculopathy; 6) Known heart failure (Grade III to IV of the New York Heart Association classification) or prolonged QTc; 7) Any type of cancer (except basal cell) in the last 5 years; 6) Refusal to give informed consent; 8) Evidence of any other unstable or clinically significant untreated immune, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric illness; 9) Antibodies positive for the human immunodeficiency virus; 10) Significant kidney or liver disease; 11) Pregnancy or lactation. INTERVENTION AND COMPARATOR: Two groups will be analyzed with a 1: 1 randomization rate. 1)Intervention: (n = 225): One 200 mg hydroxychloroquine sulfate coated tablet once daily for two months.2)Comparator (control group) (n = 225): One hydroxychloroquine placebo tablet (identical to that of the drug) once daily for two months MAIN OUTCOMES: The primary outcome of this study will be to evaluate: number and percentage of healthcare personnel presenting symptomatic and asymptomatic infection (see "Diagnosis of SARS CoV2 infection" below) by the SARS-Cov2 virus during the study observation period (8 weeks) in both treatment arms;number and percentage of healthcare personnel in each group presenting with Pneumonia with severity criteria (Curb 65 ≥2) and number and percentage of healthcare personnel requiring admission to the Intensive Care Unit (ICU) in both treatment arms. DIAGNOSIS OF SARS COV2 INFECTION: Determination of IgA, IgM and IgG type antibodies against SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Germany) every two weeks. In cases of seroconversion, a SARS-CoV-2 PCR will be performed to rule out / confirm an active infection (RT-PCR in One Step: RT performed with mastermix (Takara) and IDT probes, following protocol published and validated by the CDC Evaluation of COVID-19 in case of SARS-CoV-2 infection RANDOMISATION: Participants will be allocated to intervention and comparator groups according to a balanced randomization scheme (1: 1). The assignment will be made through a computer-generated numeric sequence for all participants BLINDING (MASKING): Both participants and investigators responsible for recruiting and monitoring participants will be blind to the assigned arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Taking into account the current high prevalence of infection in healthcare personnel in Spain (up to 15%), to detect a difference equal to or greater than 8% in the percentage estimates through a two-tailed 95% CI, with a statistical power of 80% and a dropout rate of 5%, a total of 450 participants will need to be included (250 in each arm). TRIAL STATUS: The protocol approved by the health authorities in Spain (Spanish Agency for Medicines and Health Products "AEMPS") and the Ethics and Research Committee of Cantabria (CEIm Cantabria) corresponds to version 1.1 of April 2, 2020. Currently, recruitment has not yet started, with the start scheduled for the second week of May 2020. TRIAL REGISTRATION: Eudra CT number: 2020-001704-42 (Registered on 29 March 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Asunto(s)
Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/prevención & control , Hidroxicloroquina/administración & dosificación , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Exposición Profesional/efectos adversos , Salud Laboral , Pandemias/prevención & control , Neumonía Viral/prevención & control , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Betacoronavirus/patogenicidad , Quimioprevención , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Método Doble Ciego , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Persona de Mediana Edad , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , España , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
16.
Trials ; 21(1): 470, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493514

RESUMEN

OBJECTIVES: SARS-CoV2 infection leads to a concomitant pulmonary inflammation. This inflammation is supposed to be the main driver in the pathogenesis of lung failure (Acute Respiratory Distress Syndrome) in COVID-19. Objective of this study is to evaluate the efficacy and safety of a single dose treatment with Tocilizumab in patients with severe COVID-19. We hypothesize that Tocilizumab slows down the progression of SARS-CoV-2 induced pneumonia and inflammation. We expect an improvement in pulmonary function compared to placebo-treated patients. Desirable outcomes would be that tocilizumab reduces the number of days that patients are dependent on mechanical ventilation and reduces the invasiveness of breathing assistance. Furthermore, this treatment might result in fewer admissions to intensive care units. Next to these efficacy parameters, safety of a therapy with Tocilizumab in COVID-19 patients has to be monitored closely, since immunosuppression could lead to an increased rate of bacterial infections, which could negatively influence the patient's outcome. TRIAL DESIGN: Multicentre, prospective, 2-arm randomised (ratio 1:1), double blind, placebo-controlled trial with parallel group design. PARTICIPANTS: Inclusion criteria 1.Proof of SARS-CoV2 (Symptoms and positive polymerase chain reaction (PCR))2.Severe respiratory failure: a.Ambient air SpO2 ≤ 92% orb.Need of ≥ 6l O2/min orc.NIV (non-invasive ventilation) ord.IMV (invasive mechanical ventilation)3.Age ≥ 18 years Exclusion criteria 1.Non-invasive or invasive mechanical ventilation ≥ 48 hours2.Pregnancy or breast feeding3.Liver injury or failure (AST/ALT ≥ 5x ULN)4.Leukocytes < 2 × 103/µl5.Thrombocytes < 50 × 103/µl6.Severe bacterial infection (PCT > 3ng/ml)7.Acute or chronic diverticulitis8.Immunosuppressive therapy (e.g. mycophenolate, azathioprine, methotrexate, biologicals, prednisolone >10mg/d; exceptions are: prednisolone ≤ 10mg/d, sulfasalazine or hydroxychloroquine)9.Known active or chronic tuberculosis10.Known active or chronic viral hepatitis11.Known allergic reactions to tocilizumab or its ingredients12.Life expectation of less than 1 year (independent of COVID-19)13.Participation in any other interventional clinical trial within the last 30 days before the start of this trial14.Simultaneous participation in other interventional trials (except for participation in COVID-19 trials) which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed15.Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception. The data collection of the primary follow up (28 days after randomisation) takes place during the hospital stay. Subsequently, a telephone interview on the quality of life is conducted after 6 and 12 months. Participants will be recruited from inpatients at ten medical centres in Germany. INTERVENTION AND COMPARATOR: Intervention arm: Application of 8mg/kg body weight (BW) Tocilizumab i.v. once immediately after randomisation (12 mg/kg for patients with <30kg BW; total dose should not exceed 800 mg) AND conventional treatment. Control arm: Placebo (NaCl) i.v. once immediately after randomisation AND conventional treatment. MAIN OUTCOMES: Primary endpoint is the number of ventilator free days (d) (VFD) in the first 28 days after randomisation. Non-invasive ventilation (NIV), Invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO) are defined as ventilator days. VFD's are counted as zero if the patient dies within the first 28 days. RANDOMISATION: The randomisation code will be generated by the CTU (Clinical Trials Unit, ZKS Freiburg) using the following procedure to ensure that treatment assignment is unbiased and concealed from patients and investigator staff. Randomisation will be stratified by centre and will be performed in blocks of variable length in a ratio of 1:1 within each centre. The block lengths will be documented separately and will not be disclosed to the investigators. The randomisation code will be produced by validated programs based on the Statistical Analysis System (SAS). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 100 participants will be randomised to each group (thus 200 participants in total). TRIAL STATUS: Protocol Version: V 1.2, 16.04.2020. Recruitment began 27th April 2020 and is anticipated to be completed by December 2020. TRIAL REGISTRATION: The trial was registered before trial start in trial registries (EudraCT: No. 2020-001408-41, registered 21st April 2020, and DRKS: No. DRKS00021238, registered 22nd April 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Pulmón/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Método Doble Ciego , Alemania , Interacciones Huésped-Patógeno , Humanos , Pulmón/fisiopatología , Pulmón/virología , Estudios Multicéntricos como Asunto , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/fisiopatología , Neumonía Viral/virología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Respiración Artificial , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
18.
Sensors (Basel) ; 20(11)2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32486055

RESUMEN

"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)", the novel coronavirus, is responsible for the ongoing worldwide pandemic. "World Health Organization (WHO)" assigned an "International Classification of Diseases (ICD)" code-"COVID-19"-as the name of the new disease. Coronaviruses are generally transferred by people and many diverse species of animals, including birds and mammals such as cattle, camels, cats, and bats. Infrequently, the coronavirus can be transferred from animals to humans, and then propagate among people, such as with "Middle East Respiratory Syndrome (MERS-CoV)", "Severe Acute Respiratory Syndrome (SARS-CoV)", and now with this new virus, namely "SARS-CoV-2", or human coronavirus. Its rapid spreading has sent billions of people into lockdown as health services struggle to cope up. The COVID-19 outbreak comes along with an exponential growth of new infections, as well as a growing death count. A major goal to limit the further exponential spreading is to slow down the transmission rate, which is denoted by a "spread factor (f)", and we proposed an algorithm in this study for analyzing the same. This paper addresses the potential of data science to assess the risk factors correlated with COVID-19, after analyzing existing datasets available in "ourworldindata.org (Oxford University database)", and newly simulated datasets, following the analysis of different univariate "Long Short Term Memory (LSTM)" models for forecasting new cases and resulting deaths. The result shows that vanilla, stacked, and bidirectional LSTM models outperformed multilayer LSTM models. Besides, we discuss the findings related to the statistical analysis on simulated datasets. For correlation analysis, we included features, such as external temperature, rainfall, sunshine, population, infected cases, death, country, population, area, and population density of the past three months - January, February, and March in 2020. For univariate timeseries forecasting using LSTM, we used datasets from 1 January 2020, to 22 April 2020.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Síndrome Respiratorio Agudo Grave/epidemiología , Animales , Gatos , Bovinos , Infecciones por Coronavirus/virología , Brotes de Enfermedades , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Pandemias , Neumonía Viral/virología , Virus del SRAS/patogenicidad , Síndrome Respiratorio Agudo Grave/virología , Organización Mundial de la Salud
19.
Sensors (Basel) ; 20(11)2020 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-32486477

RESUMEN

One of the key challenges of the recent COVID-19 pandemic is the ability to accurately estimate the number of infected individuals, particularly asymptomatic and/or early-stage patients. We herewith report the proof-of-concept development of a biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus. The biosensor is based on membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody. We demonstrate that the attachment of the protein to the membrane-bound antibodies resulted in a selective and considerable change in the cellular bioelectric properties measured by means of a Bioelectric Recognition Assay. The novel biosensor provided results in an ultra-rapid manner (3 min), with a detection limit of 1 fg/mL and a semi-linear range of response between 10 fg and 1 µg/mL. In addition, no cross-reactivity was observed against the SARS-CoV-2 nucleocapsid protein. Furthermore, the biosensor was configured as a ready-to-use platform, including a portable read-out device operated via smartphone/tablet. In this way, we demonstrate that the novel biosensor can be potentially applied for the mass screening of SARS-CoV-2 surface antigens without prior sample processing, therefore offering a possible solution for the timely monitoring and eventual control of the global coronavirus pandemic.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Técnicas Biosensibles , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Glicoproteína de la Espiga del Coronavirus/aislamiento & purificación , Anticuerpos Antivirales/química , Anticuerpos Antivirales/inmunología , Antígenos Virales/genética , Antígenos Virales/aislamiento & purificación , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/virología , Humanos , Límite de Detección , Pandemias , Neumonía Viral/virología , Teléfono Inteligente , Glicoproteína de la Espiga del Coronavirus/química
20.
Trials ; 21(1): 467, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493447

RESUMEN

OBJECTIVES: Comparison of the effect of hydroxychloroquine with placebo to prevent infection from the COVID -19 virus among healthcare professionals TRIAL DESIGN: Single centre, 2-arm, double-blind randomised (ratio 1:1) placebo-controlled trial PARTICIPANTS: Treatment staff who are in contact with patients and have at least 3 shifts a week in Arash hospital affiliated with Tehran University of Medical Sciences, in Iran and who consent to participate in the study. Exclusion criteria include: History of COVID -19 virus infection, clinical symptoms such as fever, nausea, dyspnea and myalgia in the past two months, history of underlying diseases hypersensitivity to hydroxychloroquine and G6PD enzyme deficiency. INTERVENTION AND COMPARATOR: Intervention group: Hydroxychloroquine 200 mg tablet of Amin Pharmaceutical. CONTROL GROUP: placebo which is completely similar in form and taste to 200 mg hydroxychloroquine tablet and is manufactured by the same factory (Amin Pharmacy). The dosage is two tablets daily, once a week for one to three months (based on the duration of the Coronavirus epidemic in Tehran). MAIN OUTCOMES: Confirmed COVID-19 virus infection using Polymerase chain reaction (PCR) test is the primary outcome. The time period for measuring the primary outcome is any infection within the trial period up to one month after taking the last dose. RANDOMISATION: The randomized block allocation method was developed using Stata version 15 software by an independent researcher, using a block size of six. Allocation to the two treatment groups will be conducted by this researcher using paper labels (random 10-digit codes) in a 1:1 ratio t The labels will be attached to the drug packages in order of randomization. Drug packages will be arranged in a box according to the randomization list. BLINDING (MASKING): Participants and caregivers are blinded to group assignment and the data will be analyzed by an independent statistical expert who is unaware of the treatment allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 282 participants will be randomised with 141 participants the Hydroxychloroquineeach intervention group and 141 participants to the placebo control group TRIAL STATUS: The protocol version number is 99-1-101-47091 and the approval ID is IR.TUMS.VCR.REC.1399.001 and recruitment began April 7, 2020, and is anticipated to be complete by August 7, 2020. TRIAL REGISTRATION: The name of the trial register is Iranian registry of clinical trial (IRCT), registration number is IRCT20120826010664N6, date of trial registration is April 7, 2020, FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/prevención & control , Hidroxicloroquina/administración & dosificación , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Exposición Profesional/efectos adversos , Salud Laboral , Pandemias/prevención & control , Neumonía Viral/prevención & control , Antivirales/efectos adversos , Betacoronavirus/patogenicidad , Quimioprevención , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Método Doble Ciego , Humanos , Hidroxicloroquina/efectos adversos , Irán , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
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