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1.
Ann Med ; 53(1): 117-134, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33095083

RESUMO

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and anti-inflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.


Assuntos
Antimaláricos/uso terapêutico , Cardiotoxicidade/etiologia , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antimaláricos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Hidroxicloroquina/farmacologia , Pandemias
2.
Medicina (Kaunas) ; 56(11)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138045

RESUMO

BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.


Assuntos
Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Coinfecção/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Mortalidade Hospitalar , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Antígenos de Bactérias/urina , Azitromicina/uso terapêutico , Betacoronavirus , Ceftriaxona/uso terapêutico , Cobicistat/uso terapêutico , Coinfecção/urina , Infecções por Coronavirus/complicações , Estudos Transversais , Darunavir/uso terapêutico , Combinação de Medicamentos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Levofloxacino/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Pandemias , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/urina , Pneumonia Viral/complicações , Estudos Retrospectivos , Ritonavir/uso terapêutico , Streptococcus pneumoniae/imunologia
3.
Trials ; 21(1): 904, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129363

RESUMO

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 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
Amidas/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pirazinas/uso terapêutico , Amidas/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Feminino , Interações Hospedeiro-Patógeno , Humanos , Hidroxicloroquina/efeitos adversos , Pacientes Internados , Masculino , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento
4.
BMC Pulm Med ; 20(1): 301, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198751

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. METHODS: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels. RESULTS: ICU patients showed a marked increase in neutrophils (1.24 × 105 ml- 1, 0.85-2.07), lower lymphocyte (0.97 × 105 ml- 1, 0.024-0.34) and macrophages fractions (0.43 × 105 ml- 1, 0.34-1.62) compared to IMW patients (0.095 × 105 ml- 1, 0.05-0.73; 0.47 × 105 ml- 1, 0.28-1.01 and 2.14 × 105 ml- 1, 1.17-3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05). CONCLUSIONS: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Infecções por Coronavirus/imunologia , Inflamação/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Leucócitos/imunologia , Pulmão/imunologia , Macrófagos Alveolares/imunologia , Pneumonia Viral/imunologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Corticosteroides/uso terapêutico , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/virologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva , Interleucina-10/imunologia , Itália , Leucócitos Mononucleares/virologia , Lopinavir/uso terapêutico , Pulmão/citologia , Pulmão/virologia , Linfócitos/imunologia , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/terapia , Prognóstico , Estudos Prospectivos , Respiração Artificial/métodos , Ritonavir/uso terapêutico , Glicoproteína da Espícula de Coronavírus/metabolismo , Taxa de Sobrevida , Vírion/metabolismo , Vírion/ultraestrutura
5.
Biomedica ; 40(Supl. 2): 80-95, 2020 10 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33152192

RESUMO

Introduction: Recently, researchers from China and France reported on the effectiveness of chloroquine and hydroxychloroquine for the inhibition of SARS-CoV-2 viral replication in vitro. Timely dissemination of scientific information is key in times of pandemic. A systematic review of the effect and safety of these drugs on COVID-19 is urgently needed. Objective: To map published studies until March 25, 2020, on the use of chloroquine and its derivates in patients with COVID-19. Materials and methods: We searched on PubMed, Embase, Lilacs, and 15 registries from the World Health Organization's International Clinical Trials Registry Platform for theoretical and empirical research in English, Spanish, Italian, French, or Portuguese until March 25, 2020, and made a narrative synthesis of the results. Results: We included 19 records and 24 trial registries (n=43) including 18,059 patients. China registered 66% (16/24) of the trials. Nine trials evaluate chloroquine exclusively and eight hydroxychloroquine. The records are comments (n=9), in vitro studies (n=3), narrative reviews (n=2), clinical guidelines (n=2), as well as a systematic review, an expert consensus, and a clinical trial. Conclusions: One small (n=26), non-randomized, and flawed clinical trial supports hydroxychloroquine use in patients with COVID-19. There is an urgent need for more clinical trial results to determine the effect and safety of chloroquine and hydroxychloroquine on COVID-19.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/farmacologia , Betacoronavirus/fisiologia , Cloroquina/efeitos adversos , Cloroquina/farmacologia , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo , Síndrome da Liberação de Citocina/tratamento farmacológico , Reposicionamento de Medicamentos , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Estudos Multicêntricos como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
6.
Pan Afr Med J ; 35(Suppl 2): 134, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33193949

RESUMO

Hydroxychloroquine is an agent used as a treatment but also considered as a prophylaxis for SARS-CoV-2 infection. We report the case of a patient who developed COVID-19 while on hydroxychloroquine for mixed connectivitis associated with spondyloarthritis. Although more work is needed before any conclusions can be drawn, this raises questions about the protective role of this drug against infection. Are they really protected against COVID-19 or will they develop pauci-symptomatic forms?


Assuntos
Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Etanercepte/uso terapêutico , Hidroxicloroquina/uso terapêutico , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Dermatopatias Virais/etiologia , Espondiloartropatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Urticária/etiologia , Antirreumáticos/efeitos adversos , Infecções por Coronavirus/complicações , Suscetibilidade a Doenças , Etanercepte/efeitos adversos , Humanos , Masculino , Doença Mista do Tecido Conjuntivo/complicações , Pandemias , Pneumonia Viral/complicações , Espondiloartropatias/complicações , Fator de Necrose Tumoral alfa/efeitos adversos , Adulto Jovem
7.
Pan Afr Med J ; 35(Suppl 2): 136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193951

RESUMO

Introduction: SARS-CoV-2 is an emerging health threat outbreak. It may cause severe viral pneumonia with Acute Respiratory Distress Syndrome requiring critical care. Aim: to describe clinical features and outcomes of critically ill patients with SARS-CoV-2 infection. Methods: it was a retrospective study carried out in the medical ICU of Farhat Hached teaching hospital between March 11 and May 7, 2020. All consecutive patients with RT-PCR confirmed COVID-19 were included. Clinical characteristics and outcomes were collected by reviewing medical records. Results: during the study period, 10 critically ill patients with COVID-19 were enrolled. Mean age, 51.8±6.3 years; 8(80%), male. The most common comorbidities were; diabetes mellitus, 6(60%), obesity 2(20%), chronic kidney disease 2(20%) and hypertension 1(10%). Mean SAPS II, 23.2±1.8. The mean arterial oxygen partial pressure to fractional inspired oxygen ratio at admission was 136.2±79.7. Noninvasive mechanical ventilation was used in 4(40%) patients and 7(70%) received invasive mechanical ventilation. Tidal volume and PEEP were set respectively within the median [IQR] of, 5.7[5.6-6.3]ml/Kg and 10.7[6.5-11.7]cm H2O. Plateau pressure was monitored in the median [IQR] of 27.9 [25.9-28.5] cm H2O. Four patients received hydroxychloroquine alone and five hydroxychloroquine associated with an antiviral. Five patients developed respectively hyperactive (n=2), hypoactive (n=2) and mixed delirium (n=1). Mortality rate was at 70%. Conclusion: this study demonstrated a particular profile of COVID-19 in the critically ill as a severe presentation in aged males with comorbidities presenting with an ARDS-like and neurological impairment with poor prognosis. The only survivals seem to have benefited from noninvasive ventilatory support.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Estado Terminal/epidemiologia , Pneumonia Viral/epidemiologia , Antivirais/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Delírio/etiologia , Diabetes Mellitus/epidemiologia , Feminino , Mortalidade Hospitalar , Hospitais de Ensino/estatística & dados numéricos , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Prognóstico , Insuficiência Renal Crônica/epidemiologia , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório do Adulto/etiologia , Estudos Retrospectivos , Escala Psicológica Aguda Simplificada , Tunísia/epidemiologia
8.
Am J Ther ; 27(6): e573-e583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33136577

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 SARS- Cov2 has taken the world by surprise. Among the first promising repurposing agents proposed for treatment and prophylaxis, 2 antimalarial agents came into limelight: chloroquine and its less toxic derivative, hydroxychloroquine (HCQ). Intense research and public debates have followed. AREAS OF UNCERTAINTY: As HCQ is still used and studied, future research may bring novel evidence, modifying the state-of-the-art. Despite the lack of a single randomized control trial (RCT) with positive results, there are currently (as for the search on 30th of August 2020) more than 250 RCT registered on ClinicalTrials.gov with HCQ in COVID patients, and more than 150 of them are "still recruiting" or "not yet recruiting" patients. DATA SOURCES: Our study combines a therapeutic evaluation of RCT data with a sociological analysis of related controversies, examining scientific and public arena discourses. RESULTS: Although any hope of a positive effect was brought exclusively by some and not all of the observational studies, none of the 7 RCT published until now have found any benefit. From a sociological perspective, the HCQ controversy is a useful case study for understanding the construction of plausibility in a cultural context polarized into competing versions of reality, with different epistemologies and ideologies. CONCLUSIONS: The results of the first RCTs have been published, and they are disappointing; beneficial effects of HCQ could not be proven either for negative conversion on polymerase chain reactions of COVID patients or for postexposure prophylaxis. The question to be asked is: how many studies do we need until HCQ is abandoned? Argumentative time work, appealing to temporal properties of HCQ including its historical use, accumulation of evidence, alternative therapeutic scenarios, and sensationalist tempo for rhetorical purpose, plays a significant role in its continuing legitimation.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Política , Medição de Risco , Resultado do Tratamento
9.
Nat Commun ; 11(1): 5284, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082342

RESUMO

Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
10.
J Coll Physicians Surg Pak ; 30(10): 124-128, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33115586

RESUMO

Chloroquine (CQ) and its derivatives such as hydroxychloroquine (HCQ) remain mainstay of therapy for malaria. These drugs are also approved for certain autoimmune diseases including systemic lupus erythematosus. The antiviral activities of these drugs and their mechanisms have been studied in vitro previously against various viruses including severe acute respiratory syndrome coronavirus (SARS-CoV). During the current coronavirus disease 2019 (COVID-19) pandemic, in vivo and in vitro investigations of these drugs have demonstrated potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The authors used the keywords to find the relevant studies, like COVID-19, SARS-CoV-2, pandemic, complications, repositioning, toxicity, overdose, treatment plan, implication strategies, prevention, chloroquine, hydroxychloroquine, clinical trials, drug interactions, and practices advice, etc., in Pubmed and Google Scholar. This review aims to provide a detailed insight of practice implications related to these drugs, which would aid healthcare professionals to ensure the safe use of these drugs during the management of patients with COVID-19 disease. Key Words: Chloroquine, Hydroxychloroquine, COVID-19, SARS-CoV-2, Practice implications.


Assuntos
Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Humanos , Pandemias
11.
Trials ; 21(1): 867, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081817

RESUMO

BACKGROUND: There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease. METHODS: The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis. DISCUSSION: This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. TRIAL REGISTRATION: ClinicalTrials.gov NCT04322396 . Registered on 26 March 2020.


Assuntos
Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Hidroxicloroquina/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Idoso , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/métodos , Antimaláricos/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus/genética , Estudos de Casos e Controles , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Dinamarca/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/efeitos adversos , Unidades de Terapia Intensiva/estatística & dados numéricos , Análise de Intenção de Tratamento/métodos , Masculino , Ventilação não Invasiva/efeitos adversos , Placebos/administração & dosagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Comportamento de Redução do Risco
12.
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
15.
J Korean Med Sci ; 35(39): e358, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045775

RESUMO

Although some comorbidities, such as diabetes mellitus, lung disease, and chronic kidney disease, are known as risk factors for poor clinical outcome in patients with coronavirus disease 2019 (COVID-19), it is unknown if human immunodeficiency virus (HIV) patients with COVID-19 would have poor prognosis than others. Rare cases of HIV patients with COVID-19 have been reported. As of May 25th, 2020, over 11,000 patients have been diagnosed with COVID-19 and over 13,000 are living with HIV in Korea. Here, we present the first HIV patient with COVID-19 in Korea. The 29-year-old Korean man had been taking Genvoya® regularly for seven years and HIV was well suppressed with CD4 counts of 555/mm³. He had mild symptoms of sore throat, dry cough, loss of taste and smell. He received hydroxychloroquine while Genvoya® was continued. Pneumonia diagnosed in chest computed tomography improved without oxygen supplementation. He was discharged on hospital day 31. HIV patients are considered as immunocompromised, but this case suggests that well controlled HIV patients have satisfactory prognosis following proper medical care.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por HIV/patologia , Pneumonia Viral/diagnóstico , Adulto , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Contagem de Linfócito CD4 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Infecções por HIV/complicações , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Prognóstico , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Tomografia Computadorizada por Raios X
16.
G Ital Nefrol ; 37(5)2020 Oct 05.
Artigo em Italiano | MEDLINE | ID: mdl-33026203

RESUMO

We report the case of a 93-year-old woman on haemodialysis treatment for more than 30 months and with multiple comorbidities who recovered from a Covid-19 infection without any significant clinical problems. The patient has shown a delay in viral clearance with swab test negativization (confirmed) after 33 days; after testing positive again, she has resulted persistently negative, (confirmed after 49 days). After the first negative swab, IgG and IgM antibodies have been found; these have remained persistently positive after a month. As well as highlighting an unexpected resilience in an extremely fragile context, the analysis of this case draws attention to patients' management and, potentially, to the need to arrange dialysis treatments in isolation for some time after their "laboratory recovery".


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Diálise Renal , Sobreviventes , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Calcitriol/uso terapêutico , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Quimioterapia Combinada , Feminino , Heparina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Nasofaringe/virologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Fatores de Tempo
17.
Cir Cir ; 88(5): 569-575, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064694

RESUMO

Objective: To describe the clinical characteristics and management of severe COVID-19 patients. Method: Observational, descriptive, longitudinal, and retrospective study. Results: 56 patients were admitted, of whom 80.3% (n = 45) were males with a mean age of 58 years [46-67]. The main comorbidities were obesity, high blood pressure, and diabetes. Symptoms onset time at admittance to the ICU was 9 [7-14] days, of which the most frequent were dyspnea, fever, and dry cough. Laboratory data were lymphopenia; elevation of LDH, fibrinogen, D-dimer, ferritin and CRP. 100% of the patients required mechanical ventilation, the median mechanical ventilation time was 12 [6-17] days, and 66% (n= 37) required a prone position. The pharmacological treatment was mainly based on azithromycin, hydroxychloroquine, tocilizumab and steroids. The most frequent complications were acute kidney injury, venous thromboembolism and acute myocardial infarction. Mortality rate was 17.8% (n = 10). Conclusion: The characteristics of the critically ill patients in our hospital were mostly elderly and obese, with the variables of higher SOFA score and acute kidney injury associated with higher mortality.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral/terapia , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Corticosteroides/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Terapia Combinada , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Feminino , Mortalidade Hospitalar , Hospitais Universitários/organização & administração , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Respiração Artificial , Avaliação de Sintomas
18.
J Immunol Res ; 2020: 4582612, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062720

RESUMO

Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of 4-aminoquinoline compounds with over 60 years of safe clinical usage. CQ and HCQ are able to inhibit the production of cytokines such as interleukin- (IL-) 1, IL-2, IL-6, IL-17, and IL-22. Also, CQ and HCQ inhibit the production of interferon- (IFN-) α and IFN-γ and/or tumor necrotizing factor- (TNF-) α. Furthermore, CQ blocks the production of prostaglandins (PGs) in the intact cell by inhibiting substrate accessibility of arachidonic acid necessary for the production of PGs. Moreover, CQ affects the stability between T-helper cell (Th) 1 and Th2 cytokine secretion by augmenting IL-10 production in peripheral blood mononuclear cells (PBMCs). Additionally, CQ is capable of blocking lipopolysaccharide- (LPS-) triggered stimulation of extracellular signal-modulated extracellular signal-regulated kinases 1/2 in human PBMCs. HCQ at clinical levels effectively blocks CpG-triggered class-switched memory B-cells from differentiating into plasmablasts as well as producing IgG. Also, HCQ inhibits cytokine generation from all the B-cell subsets. IgM memory B-cells exhibits the utmost cytokine production. Nevertheless, CQ triggers the production of reactive oxygen species. A rare, but serious, side effect of CQ or HCQ in nondiabetic patients is hypoglycaemia. Thus, in critically ill patients, CQ and HCQ are most likely to deplete all the energy stores of the body leaving the patient very weak and sicker. We advocate that, during clinical usage of CQ and HCQ in critically ill patients, it is very essential to strengthen the CQ or HCQ with glucose infusion. CQ and HCQ are thus potential inhibitors of the COVID-19 cytokine storm.


Assuntos
Anti-Inflamatórios/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/biossíntese , Humanos , Pandemias , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos
19.
PLoS One ; 15(10): e0240266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007039

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) is widely used in the treatment of malaria, rheumatologic disease such as lupus, and most recently, COVID-19. These uses raise concerns about its safe use in the setting of glucose-6-phosphate dehydrogenase (G6PD) deficiency, especially as 11% of African American men carry the G6PD A- variant. However, limited data exist regarding the safety of HCQ in this population. STUDY DESIGN AND METHODS: Recently, we created a novel "humanized" mouse model containing the G6PD deficiency A- variant (Val68Met) using CRISPR technology. We tested the effects of high-dose HCQ administration over 5 days on hemolysis in our novel G6PD A- mice. In addition to standard hematologic parameters including plasma hemoglobin, erythrocyte methemoglobin, and reticulocytes, hepatic and renal function were assessed after HCQ. RESULTS: Residual erythrocyte G6PD activity in G6PD A- mice was ~6% compared to wild-type (WT) littermates. Importantly, we found no evidence of clinically significant intravascular hemolysis, methemoglobinemia, or organ damage in response to high-dose HCQ. CONCLUSIONS: Though the effects of high doses over prolonged periods was not assessed, this study provides early, novel safety data of the use of HCQ in the setting of G6PD deficiency secondary to G6PD A-. In addition to novel safety data for HCQ, to our knowledge, we are the first to present the creation of a "humanized" murine model of G6PD deficiency.


Assuntos
Modelos Animais de Doenças , Deficiência de Glucosefosfato Desidrogenase/patologia , Hidroxicloroquina/efeitos adversos , Afro-Americanos , Animais , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Camundongos , Pandemias , Pneumonia Viral/tratamento farmacológico
20.
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
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