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1.
J Med Case Rep ; 14(1): 210, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33138853

RESUMO

BACKGROUND: Since the World Health Organization declared a global pandemic due to the novel coronavirus disease2019, there have been targeted efforts to establish management modalities. Hydroxychloroquine has been suggested as a possible treatment; however, it is associated with multiple adverse reactions. We report a rare case of a patient with acute generalized exanthematous pustulosis with Stevens-Johnson syndrome due to hydroxychloroquine. Acute generalized exanthematous pustulosis is characterized by acute onset of a generalized rash that is pustular and erosive in nature, affecting limbs; trunk; face; and, less often, mucosal membranes. Although rare, it is important to be mindful of this side effect because the diagnosis is often delayed, and the disease has the potential to be life-threatening. CASE PRESENTATION: A 68-year-old American woman presented to our hospital with a painful, rapidly spreading rash. Its morphologic features included erythema multiforme-like lesions with extensive skin sloughing in various regions of the head, neck, and trunk and mucosal involvement. Her Nikolsky sign was negative, and she had no evidence of lesions on areas of skin trauma. Four weeks prior, she had been initiated on hydroxychloroquine for a presumed diagnosis of cutaneous sarcoidosis. Three punch biopsies of the head and neck area revealed subcorneal pustules consistent with acute generalized exanthematous pustulosis. Treatment began with high doses of methylprednisolone, leading to only minimal improvement of existing areas and ongoing spread to new areas. Treatment with intravenous immunoglobulin was initiated, at which point disease stability was achieved. The patient's rash ultimately resolved, as did her cutaneous pain and pruritus. CONCLUSIONS: Among many potential adverse reactions involving hydroxychloroquine, cutaneous side effects are varied and can lead to significant morbidity or even death. The drug is currently being investigated in a multitude of trials for coronavirus disease2019 treatment, prevention, and prophylaxis after exposure to severe acute respiratory syndrome coronavirus 2. Acute generalized exanthematous pustulosis is a rare side effect of hydroxychloroquine, and even fewer cases demonstrate histologic evidence of acute generalized exanthematous pustulosis while clinically presenting with Stevens-Johnson syndrome. Patients who develop Stevens-Johnson syndrome/toxic epidermal necrolysis require best supportive care with aggressive fluid and electrolyte replacement and prevention of further breakdown of the skin barrier. With the potential of widespread hydroxychloroquine use, it is important that providers be aware of its potential severe adverse drug reactions.


Assuntos
Pustulose Exantematosa Aguda Generalizada , Infecções por Coronavirus/epidemiologia , Hidroxicloroquina , Imunoglobulinas Intravenosas/administração & dosagem , Metilprednisolona/administração & dosagem , Pneumonia Viral/epidemiologia , Sarcoidose/tratamento farmacológico , Síndrome de Stevens-Johnson , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/fisiopatologia , Pustulose Exantematosa Aguda Generalizada/terapia , Idoso , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Biópsia/métodos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos , Pandemias , Pele/patologia , Dermatopatias/tratamento farmacológico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/fisiopatologia , Síndrome de Stevens-Johnson/terapia , Resultado do Tratamento
2.
Klin Onkol ; 33(5): 386-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108884

RESUMO

BACKGROUND: In December 2019 a new strain of coronavirus SARS-CoV-2 has emerged and affected health care worldwide. Patients with cancer and other comorbidities are at increased risk for adverse outcomes in this infection. CASE: In this case report we present a 75-year-old patient with a localized gastric adenocarcinoma, currently treated by perioperative chemotherapy regimen, who had an rT-PCR proven novel coronavirus SARS-CoV-2 infection. Laboratory and radiologic assessments were performed in order to assess disease severity; however, the findings were not altered in accordance with the findings associated with COVID-19 disease. RESULTS: On the first hospital day the patient had a low grade fever with chills. Subsequently a pharmacological therapy with hydroxychloroquine and azithromycin was started. After pharmacologic and symptomatic treatment, the patient was reassessed for SARS-CoV-2, with negative results. At discharge, the patient was ordered a 14-day mandatory quarantine. After 57 days of follow-up, the patient underwent a new rapid antibody test by Acro Biotech inc., which gave negative results for IgM and IgG. CONCLUSION: An infection with SARS-CoV-2 is associated with a more severe disease in patients with comorbidities and cancer; however, this case patient had a mild course of COVID-19 disease. The aim of this case report is to share the information on the clinical course and outcomes of a patient with malignancy. Rapid spreading of information is crucial in the management of COVID-19.


Assuntos
Adenocarcinoma/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Neoplasias Gástricas/complicações , Idoso , Azitromicina/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/administração & dosagem , Masculino , Pandemias , Alta do Paciente , Pneumonia Viral/tratamento farmacológico , Eslováquia , Resultado do Tratamento
3.
Trials ; 21(1): 866, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081849

RESUMO

OBJECTIVES: 1. To compare the safety and efficacy of Hydroxychloroquine with Ribavirin and standard treatment in patients with non-severe COVID-19 infection 2. To compare the safety and efficacy of standard treatment, Lopinavir-ritonavir with Ribavarin, and Hydroxychloroquine with Ribavirin in patients with severe COVID-19 infection TRIAL DESIGN: The study is an Open label, Parallel arm design, stratified randomised controlled trial. Patients will be categorised as non-severe or severe based on predefined criteria. Those who satisfy all inclusion criteria and no exclusion criteria in the respective categories, will be randomly assigned to one of the three treatment groups in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. PARTICIPANTS: The trial will be undertaken in a tertiary care center of the country where both Covid and non-Covid patients are getting treated. All patients who are confirmed positive and admitted will be screened for the eligibility criteria and will be enrolled in the study after a written informed consent. Patients will be categorised as non-severe or severe based on predefined criteria. INCLUSION CRITERIA (ALL REQUIRED): 1. Age ≥18 years at time of participation in the study 2. Laboratory (RT-PCR) confirmed infection with SARS-CoV-2 3. Symptomatic (severe or non-severe) Covid-19 disease 4. Willingness of study participant to accept randomization to any assigned treatment arm EXCLUSION CRITERIA: 1. Use of medications that are contraindicated with Lopinavir/Ritonavir, Hydroxychloroquine/Chloroquine, or Ribavirin and that cannot be replaced or stopped 2. Patient already on antiretroviral therapy with Lopinavir-Ritonavir based regimen or on Hydroxychloroquine/Chloroquine or on Ribavirin 3. Any known contraindication to test drugs such as retinopathy and QT prolongation 4. Known allergic reaction or inability to take orally of Lopinavir-ritonavir, Hydroxychloroquine/ Chloroquine, Ribavarin 5. Pregnant or breastfeeding females 6. Receipt of any experimental treatment for 2019-nCoV (off-label, compassionate use, or trial related) within 30 days prior to participation in the present study or want to participate after enrolment INTERVENTION AND COMPARATOR: Two therapeutic interventions for non-severe category and three for severe category as described below NON-SEVERE TREATMENT ARMS (NS-GROUP): Treatment Arm Drug A Standard Treatment (STNS) B Hydroxychloroquine 400 mg twice on first day followed by 400 mg per oral daily for 10 days + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STNS) Standard Treatment for non-severe cases (STNS): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Hydration, Proper Nutrition, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. SEVERE GROUP TREATMENT ARMS (S-GROUP): Treatment Arm Drug A Standard Treatment (STs) B Hydroxychloroquine 400mg BD on day1 followed by 400 mg once daily + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs) C Lopinavir(200mg) + Ritonavir (50mg) two tablets twice daily+ Ribavirin (1.2g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs)6 Standard Treatment for severe patients (STs): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Fluid Therapy, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Oxygen supplementation (As required), Invasive ventilation (As required), Antibiotic agents for other associated infections (according to 2019 ATS/IDSA guidelines for non-ICU and ICU patients), Vasopressor support, Renal-replacement therapy, Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. MAIN OUTCOMES: Primary endpoints: (1) Time to Clinical recovery (TTCR) defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, oxygen saturation, and alleviation of cough, sustained for at least 72 hours. (2) Time to SARS-CoV-2 RT-PCR negative in upper respiratory tract specimen, time to laboratory recovery of each organ involvement. Secondary Endpoints: All causes mortality, Frequency of respiratory progression (defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support), time to defervescence (in those with fever at enrolment), frequency of requirement for supplemental oxygen or non-invasive ventilation, frequency of requirement for mechanical ventilation, frequency of serious adverse events as per DAIDS table grade of severity. Outcomes are monitored for 28 days from the time of enrolment into the study OR until the patient is discharged or death whichever is longer. RANDOMIZATION: The randomization will be done using a secured central computer-based randomization using a secure website using a central, computer-based randomisation program in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. BLINDING (MASKING): This is an open labelled study i.e. Study assigned treatment will be known to the research team, the investigators and participants. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Since it is an exploratory trial as COVID-19 being a new disease, all patients who came under the purview of the inclusion criteria within the study period (5 months duration of the recruitment period of the total 6 months duration of the study i.e. from the month of June, 2020 to October 2020) and who have consented for the study will be included. TRIAL STATUS: Protocol version:1.0 Recruitment start: June 3rd, 2020 (Ongoing) Recruitment finish (expected): October 31st, 2020 TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI): CTRI/2020/06/025575 . Registration on 03 June 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.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Ribavirina/uso terapêutico , Administração Oral , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Antivirais/administração & dosagem , Betacoronavirus/genética , Protocolos Clínicos , Terapia Combinada , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Índia/epidemiologia , Consentimento Livre e Esclarecido , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Ribavirina/administração & dosagem , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Segurança , Fatores de Tempo , Resultado do Tratamento
4.
Med Hypotheses ; 143: 110110, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33017904

RESUMO

Current formulations and dose regimens of hydroxychloroquine (HCQ) put patients at risk of harm. An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Further, almost all of the trials registered do not consider dosage adjustment in the elderly, a patient population most likely to require HCQ treatment. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. As this simple formulation progressed to phase II studies, safety data can be used to immediately enable phase II trials in COVID-19.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pulmão/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Administração por Inalação , Adolescente , Adulto , Idoso , Asma/tratamento farmacológico , Betacoronavirus , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Segurança do Paciente , Resultado do Tratamento , Adulto Jovem
5.
Front Immunol ; 11: 560381, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072099

RESUMO

Background: Emerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind. Methods: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group. Results: sCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not. Conclusions: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients.


Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Betacoronavirus , Infecções por Coronavirus , Receptores de Lipopolissacarídeos , Pandemias , Pneumonia Viral , Receptores de Superfície Celular , Corticosteroides/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígenos CD/sangue , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/imunologia , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Unidades de Terapia Intensiva , Interleucina-6/sangue , Interleucina-6/imunologia , Receptores de Lipopolissacarídeos/sangue , Receptores de Lipopolissacarídeos/imunologia , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Admissão do Paciente , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/imunologia , Fatores de Tempo
6.
PLoS One ; 15(10): e0239389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33057434

RESUMO

INTRODUCTION: The COVID-19 pandemic has posed major challenges to all aspects of healthcare. Malta's population density, large proportion of elderly and high prevalence of diabetes and obesity put the country at risk of uncontrolled viral transmission and high mortality. Despite this, Malta achieved low mortality rates compared to figures overseas. The aim of this paper is to identify key factors that contributed to these favorable outcomes. METHODS: This is a retrospective, observational, nationwide study which evaluates outcomes of patients during the first wave of the pandemic in Malta, from the 7th of March to the 24th of April 2020. Data was collected on demographics and mode of transmission. Hospitalization rates to Malta's main general hospital, Mater Dei Hospital, length of in-hospital stay, intensive care unit admissions and 30-day mortality were also analyzed. RESULTS: There were 447 confirmed cases in total; 19.5% imported, 74.2% related to community transmission and 6.3% nosocomially transmitted. Ninety-three patients (20.8%) were hospitalized, of which 4 were children. Patients with moderate-severe disease received hydroxychloroquine and azithromycin, in line with evidence available at the time. A total of 4 deaths were recorded, resulting in an all-cause mortality of 0.89%. Importantly, all admitted patients with moderate-severe disease survived to 30-day follow up. CONCLUSION: Effective public health interventions, widespread testing, remote surveillance of patients in the community and a low threshold for admission are likely to have contributed to these favorable outcomes. Hospital infection control measures were key in preventing significant nosocomial spread. These concepts can potentially be applied to stem future outbreaks of viral diseases. Patients with moderate-severe disease had excellent outcomes with no deaths reported at 30-day follow up.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Uso de Medicamentos/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Malta , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Análise de Sobrevida
7.
Rev Peru Med Exp Salud Publica ; 37(2): 302-311, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32876222

RESUMO

During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.


Assuntos
Infecções por Coronavirus/epidemiologia , Inflamação/virologia , Pneumonia Viral/epidemiologia , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Humanos , Hidroxicloroquina/administração & dosagem , Inflamação/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia
8.
Medicine (Baltimore) ; 99(35): e21810, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871902

RESUMO

RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.


Assuntos
Azitromicina/administração & dosagem , Betacoronavirus , Infecções por Coronavirus , Exantema , Glucocorticoides/administração & dosagem , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Pandemias , Pneumonia Viral , Ritonavir/administração & dosagem , Administração Tópica , Adulto , Antivirais/administração & dosagem , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Exantema/diagnóstico , Exantema/tratamento farmacológico , Exantema/etiologia , Exantema/imunologia , Feminino , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Avaliação de Sintomas/métodos , Resultado do Tratamento
9.
J Cardiovasc Med (Hagerstown) ; 21(10): 765-771, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32890069

RESUMO

AIMS: The aim of this study was to evaluate the clinical course of COVID-19 in patients who had recently undergone a cardiac procedure and were inpatients in a cardiac rehabilitation department. METHODS: All patients hospitalized from 1 February to 15 March 2020 were included in the study (n = 35; 16 men; mean age 78 years). The overall population was divided into two groups: group 1 included 10 patients who presented with a clinical picture of COVID-19 infection and were isolated, and group 2 included 25 patients who were COVID-19-negative. In group 1, nine patients were on chronic oral anticoagulant therapy and one patient was on acetylsalicylic acid (ASA) and clopidogrel. A chest computed tomography scan revealed interstitial pneumonia in all 10 patients. RESULTS: During hospitalization, COVID-19 patients received azithromycin and hydroxychloroquine in addition to their ongoing therapy. Only the patient on ASA with clopidogrel therapy was transferred to the ICU for mechanical ventilation because of worsening respiratory failure, and subsequently died from cardiorespiratory arrest. All other patients on chronic anticoagulant therapy recovered and were discharged. CONCLUSION: Our study suggests that COVID-19 patients on chronic anticoagulant therapy may have a more favorable and less complicated clinical course. Further prospective studies are warranted to confirm this preliminary observation.


Assuntos
Anticoagulantes/uso terapêutico , Azitromicina/administração & dosagem , Procedimentos Cirúrgicos Cardíacos , Infecções por Coronavirus , Hidroxicloroquina/administração & dosagem , Pandemias , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral , Complicações Pós-Operatórias , Idoso , Anti-Infecciosos/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Terapia Combinada/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/virologia , Tomografia Computadorizada por Raios X/métodos
10.
Med. clín (Ed. impr.) ; 155(5): 202-204, sept. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-188495

RESUMO

ANTECEDENTES Y OBJETIVO: La pandemia por Covid-19 afecta especialmente a pacientes con cáncer con mayor incidencia y mortalidad según series publicadas de focos originales de pandemia. El estudio pretende conocer la mortalidad en nuestro centro por covid-19 en pacientes con cáncer durante las primeras3 semanas de epidemia. MATERIAL Y MÉTODOS: Se han revisado los pacientes con cáncer fallecidos por covid-19 durante el periodo de análisis describiendo las características oncológicas, de la infección por covid-19 y de los tratamientos instaurados. RESULTADOS: Casos confirmados covid-19: 1069 con 132 fallecimientos (12,3%). Con cáncer 36 pacientes (3.4%), 15 fallecidos (41,6%). De los fallecidos solo6 pacientes (40%) se encontraban en tratamiento activo. El tumor más frecuente asociado fue pulmón (8/15 pacientes, 53,3%), 11 con enfermedad metastásica (11/15, 73,3%). El 40% (6/15) no recibió tratamiento específico contra covid-19, el resto fue tratado con los protocolos activos. CONCLUSIÓN: La mortalidad por covid-19 en pacientes con cáncer casi cuadriplica la de la población general. Hasta disponer de tratamientos eficaces o una vacuna efectiva la única posibilidad de proteger a nuestros pacientes es impedir el contagio con las medidas adecuadas


BACKGROUND AND OBJECTIVE: The Covid-19 pandemic especially affects cancer patients with higher incidence and mortality according to published series of original pandemic foci. The study aims to determine the mortality in our center due to covid-19 in cancer patients during the first 3 weeks of the epidemic. MATERIAL AND METHODS: The cancer patients who died of covid-19 during the analysis period have been reviewed describing the oncological and the covid-19 infection characteristics and the treatments established. RESULTS: Confirmed cases covid-19: 1069 with 132 deaths (12.3%). With cancer 36 patients (3.4%), 15 deceased (41.6%). Of the deceased, only 6 patients (40%) were in active treatment. The most frequent associated tumor was lung (8/15 patients, 53.3%), 11 with metastatic disease (11/15, 73.3%). No specific treatment wasestablished in 40 % (6/15) of the patients. The rest of them received treatments with the active protocols. CONCLUSION: Covid-19 mortality in cancer patients is almost four times higher than that of the general population. Until we have effective treatments or an effective vaccine, the only possibility to protect our patients is to prevent the infection with the appropriate measures


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/mortalidade , Neoplasias/epidemiologia , Comorbidade , Neoplasias/complicações , Febre/complicações , Tosse/complicações , Dispneia/complicações , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Azitromicina/administração & dosagem , Antineoplásicos/administração & dosagem , Unidades de Terapia Intensiva/estatística & dados numéricos
11.
J Bras Nefrol ; 42(2 suppl 1): 49-50, 2020 Aug 26.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32877501

RESUMO

Chloroquine and hydroxychloroquine have shown promising preliminary results and have been discussed as therapeutic options for patients with Covid-19. Despite the lack of robust evidence demonstrating the benefits and justifying the use of one of these drugs, the final decision is the responsibility of the attending physician and should be individualized and shared, whenever possible. This position statement recommends dosage adjustment for these drugs in the context of renal impairment.


Assuntos
Antimaláricos/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Insuficiência Renal , Brasil , Humanos , Nefrologia , Pandemias , Sociedades Médicas
12.
Toxicol Appl Pharmacol ; 406: 115237, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920000

RESUMO

Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological and toxicological profile in SARS-CoV-2 - infected patients are still unknown. Thus, by using in silico toxicogenomic data-mining approach, we aimed to assess both risks and benefits of the COVID-19 treatment with the most promising candidate drugs combinations: lopinavir/ritonavir and chloroquine/hydroxychloroquine + azithromycin. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite portal (https://toppgene.cchmc.org) served as a foundation in our research. Our results have demonstrated that lopinavir/ritonavir increased the expression of the genes involved in immune response and lipid metabolism (IL6, ICAM1, CCL2, TNF, APOA1, etc.). Chloroquine/hydroxychloroquine + azithromycin interacted with 6 genes (CCL2, CTSB, CXCL8, IL1B, IL6 and TNF), whereas chloroquine and azithromycin affected two additional genes (BCL2L1 and CYP3A4), which might be a reason behind a greater number of consequential diseases. In contrast to lopinavir/ritonavir, chloroquine/hydroxychloroquine + azithromycin downregulated the expression of TNF and IL6. As expected, inflammation, cardiotoxicity, and dyslipidaemias were revealed as the main risks of lopinavir/ritonavir treatment, while chloroquine/hydroxychloroquine + azithromycin therapy was additionally linked to gastrointestinal and skin diseases. According to our results, these drug combinations should be administrated with caution to patients suffering from cardiovascular problems, autoimmune diseases, or acquired and hereditary lipid disorders.


Assuntos
Betacoronavirus , Simulação por Computador , Mineração de Dados/métodos , Toxicogenética/métodos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Bases de Dados Genéticas , Quimioterapia Combinada , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
13.
Am J Case Rep ; 21: e927304, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32978364

RESUMO

BACKGROUND This case series describes 5 patients with SARS-CoV-2 infection and COVID-19 in Ecuador who had been treated with hydroxychloroquine for systemic lupus erythematosus (SLE) prior to their COVID-19 illness. CASE REPORT Case #1 reports a 29-year-old woman who had been treated with 200 mg of hydroxychloroquine per day for 1 year and presented with flu-like symptoms, chest pain, fever, odynophagia, asthenia, dry cough, and chills. Case #2 was a 34-year-old woman whose treatment for SLE included 200 mg of hydroxychloroquine per day since 2017. She arrived at the clinic with a dry cough, asthenia, and myalgias. Case #3 was a 24-year-old woman who had been using 200 mg of hydroxychloroquine per day since 2010. She presented with asthenia, myalgias, headaches, hypogeusia, and anosmia. Case #4 was a 39-year-old woman taking 200 mg of hydroxychloroquine every day for SLE who presented with dyspnea, chest pain, odynophagia, hypogeusia, anosmia, diarrhea, and fever. Case #5 was a 46-year-old woman who had been taking 200 mg of hydroxychloroquine since 2019. She came to our hospital complaining of chest pain, fever, and dyspnea. In all 5 patients, SARS-CoV-2 infection was confirmed with a nasopharyngeal SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test using the Cepheid/GeneXpert system. CONCLUSIONS All 5 of our patients with SLE who were taking hydroxychloroquine presented with SARS-CoV-2 infection and symptoms of COVID-19. This case series provides support for a lack of prevention of COVID-19 by hydroxychloroquine.


Assuntos
Infecções por Coronavirus/prevenção & controle , Hidroxicloroquina/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adulto , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Dispneia/diagnóstico , Dispneia/etiologia , Equador , Serviço Hospitalar de Emergência , Feminino , Febre/diagnóstico , Febre/etiologia , Humanos , Pessoa de Meia-Idade , Pandemias/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real/métodos , Medição de Risco , Amostragem , Falha de Tratamento , Adulto Jovem
14.
J Infect Chemother ; 26(12): 1319-1323, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32893123

RESUMO

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Guanidinas/administração & dosagem , Hemodiafiltração/métodos , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Antivirais/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Humanos , Japão , Lopinavir/administração & dosagem , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Insuficiência Respiratória/complicações , Ritonavir/administração & dosagem , Resultado do Tratamento
15.
J Interferon Cytokine Res ; 40(10): 469-471, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32881593

RESUMO

Coronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently emerged as a global health threat. To address this health emergency, various therapeutic approaches are currently under investigation. There is limited evidence on the effectiveness of hydroxychloroquine (HCQ) and chloroquine (CQ) as COVID-19 therapies, and thus World Health Organization (WHO) mentioned that "Current data shows that this drug does not reduce deaths among hospitalized COVID-19 patients, nor help people with mild or moderate disease." CQ and HCQ are typically used for the treatment of malaria but have been recognized for certain beneficial effects in COVID-19 patients based on some clinical outcomes from the clinical treatment of COVID-19. A standard dose of HCQ has been proven effective and less toxic than CQ in COVID-19 patients; however, a comprehensive understanding of a patient's clinical condition is necessary. Based on several hospital findings, the Food and Drug Administration (FDA) has officially cancelled the emergency use authorization for HCQ and CQ for treating hospitalized COVID-19 patients on June 15, 2020. In this review, we highlight both pros and cons of the clinical use of CQ and HCQ in COVID-19 patients.


Assuntos
Anti-Infecciosos/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Anti-Infecciosos/efeitos adversos , Azitromicina/uso terapêutico , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/patogenicidade , Cloroquina/efeitos adversos , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Resultado do Tratamento
18.
Circ Arrhythm Electrophysiol ; 13(10): e008686, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907357

RESUMO

BACKGROUND: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. METHODS: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies. RESULTS: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. CONCLUSIONS: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.


Assuntos
Antivirais/administração & dosagem , Eletrocardiografia , Coração Fetal/efeitos dos fármacos , Bloqueio Cardíaco/congênito , Frequência Cardíaca/efeitos dos fármacos , Hidroxicloroquina/administração & dosagem , Antivirais/efeitos adversos , Antivirais/sangue , Cardiotoxicidade , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Sangue Fetal/metabolismo , Coração Fetal/fisiopatologia , Idade Gestacional , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Bloqueio Cardíaco/prevenção & controle , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/sangue , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Nat Commun ; 11(1): 4249, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843618

RESUMO

Aberrant cell cycle machinery and loss of the CDKN2A tumor suppressor locus make CDK4/6 a potential target in pancreatic ductal adenocarcinoma (PDAC). However, a vast majority of PDAC cases do not harbor a durable response to monotherapy of CDK4/6 inhibitor. Utilizing remote loading to co-encapsulate CDK4/6 inhibitor palbociclib (PAL) and an autophagy inhibitor hydroxychloroquine (HCQ), we demonstrate a ratiometrically designed mesoporous silica nanoformulation with synergistic efficacy in subcutaneous and orthotopic PDAC mouse models. The synergism is attributed to the effective intratumoral buildup of PAL/HCQ, which otherwise exhibit distinctly different circulatory and biodistribution profile. PAL/HCQ co-delivery nanoparticles lead to the most effective shrinkage of PDAC compared to various controls, including free drug mixture. Immunohistochemistry reveals that PAL/HCQ co-delivery nanoparticles trigger anti-apoptotic pathway after repetitive intravenous administrations in mice. When combined with a Bcl inhibitor, the performance of co-delivery nanoparticles is further improved, leading to a long-lasting anti-PDAC effect in vivo.


Assuntos
Autofagia/efeitos dos fármacos , Carcinoma Ductal Pancreático/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Sistemas de Liberação de Medicamentos , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/química , Hidroxicloroquina/farmacologia , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Piperazinas/administração & dosagem , Piperazinas/química , Piperazinas/farmacologia , Piridinas/administração & dosagem , Piridinas/química , Piridinas/farmacologia , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Resultado do Tratamento
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