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1.
FASEB J ; 34(5): 6027-6037, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32350928

RESUMO

There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Conjuntos de Dados como Assunto/normas , Coração/efeitos dos fármacos , Humanos , Hidroxicloroquina/farmacologia , Imunidade Inata/efeitos dos fármacos , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
3.
A A Pract ; 14(7): e01227, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32371823

RESUMO

A 17-year-old healthy girl underwent an uneventful esthetic septorhinoplasty. She was easily extubated and transferred to the postanesthesia care unit (PACU) with oxygen saturation (SpO2) of 96%. About 30 minutes after arrival in the PACU, she developed dyspnea with SpO2 of 84% and promptly received oxygen with bilevel positive airway pressure in conjunction with low-dose corticosteroid. The subsequent chest computed tomography (CT) revealed bilateral patchy infiltrates similar to the radiologic findings of Coronavirus Disease 2019 (COVID-19). Finally, a reverse transcriptase polymerase chain reaction (RT-PCR) of a pharyngeal specimen confirmed the diagnosis of COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Coronavirus/isolamento & purificação , Dispneia/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/complicações , Tomografia Computadorizada por Raios X/métodos , Adolescente , Extubação , Betacoronavirus , Técnicas de Laboratório Clínico , Coronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Dispneia/etiologia , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Oxigênio/uso terapêutico , Pandemias , Faringe/virologia , Cuidados Pós-Operatórios , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(19): e20207, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384516

RESUMO

RATIONALE: Novel coronavirus 2019 (COVID-19) also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, non-segmented positive-sense RNA virus belonging to the beta-coronaviridae family. This virus is known to cause severe bilateral pneumonia and acute respiratory distress syndrome (ARDS) which can lead to difficulty breathing requiring mechanical ventilation and intensive care unit management. PATIENT CONCERNS: A 77-year-old female with a history of hypertension and hyperlipidemia who presented as a transfer to our hospital facility with worsening fevers, cough, and respiratory distress. DIAGNOSIS: Chest X-rays revealed bilateral infiltrates worse at the lung bases and CT scan of the chest showed bilateral ground-glass opacities consistent with COVID-19. While our testing revealed a negative COVID-19 result at our institution, the result at a previous hospital returned a positive result. INTERVENTIONS: She was being treated aggressively in the intensive care unit with high dose intravenous ascorbic acid, hydroxychloroquine, and anti-interleukin-6 monoclonal antibody. She also received a loading dose of remdesivir however was unable to complete the course due to organ failure and requirement of vasopressors for hemodynamic stability. OUTCOMES: She remained critically ill and was eventually placed on comfort care as per the family's wishes and passed away. LESSONS: With a rapidly growing death rate and more than 200,000 confirmed cases worldwide, COVID-19 has become a global pandemic and major hit to our healthcare systems. While several companies have already begun vaccine trials and healthcare facilities have been using a wide-range of medications to treat the virus and symptoms, there is not yet an approved medication regimen for COVID-19 infections. The alarming increase in cases per day adds additional pressure to find a cure and decrease the global health burden and mortality rate.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Evolução Fatal , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem
5.
Indian J Med Ethics ; V(2): 100-102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32393448

RESUMO

The National Task Force for Covid-19 of the Indian Council of Medical Research (ICMR) in a bulletin dated March 21, 2020 recommended the use of hydroxychloroquine for prophylaxis in asymptomatic health care workers caring for suspected or confirmed patients and household contacts of confirmed patients. This is cause for concern with regard to bioethics and good clinical practice. The evidence for the efficacy of chloroquine and hydroxychloroquine is currently derived from open label trials and cell culture studies with no conclusive evidence available from randomised clinical trials. Hydroxychloroquine also carries contraindications in the case of conditions such as maculopathy, retinopathy and QTc prolongation and should be used with caution in vulnerable populations such as children, pregnancy, lactation and the elderly. Despite this, there has been a rush to procure and self-medicate with hydroxychloroquine, which has been addressed by the National Task Force. The WHO and the FDA have not found adequate evidence to recommend any specific medication for the treatment of Covid-19. While further evidence is awaited, including from trials registered with the FDA and the ICMR, it is recommended that the administration of hydroxychloroquine for chemo-prophylaxis be considered on a case by case basis with monitoring by a registered medical practitioner including electrocardiography (ECG). The potential for retinal and cardiac toxicity must also be borne in mind. It is further recommended that a public advisory regarding the need for caution in chemo-prophylaxis be made available in the public domain. Keywords: Coronavirus, Covid-19, SARS-CoV-2, hydroxychloroquine, chloroquine, chemoprophylaxis, bioethics, evidence- based medicine.


Assuntos
Cloroquina , Infecções por Coronavirus , Hidroxicloroquina , Pandemias , Pneumonia Viral , Betacoronavirus , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Índia , Seleção de Pacientes , Pneumonia Viral/tratamento farmacológico , Guias de Prática Clínica como Assunto , Automedicação
8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 215-219, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32391667

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). METHODS: We prospectively enrolled 30 treatment-naïve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1:1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). RESULTS: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1,9) days in HCQ group, which is comparable to that in the control group [2 (1,4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0,2) day after hospitalization, which was also comparable to that in the control group [1 (0,3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). CONCLUSIONS: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.


Assuntos
Betacoronavirus , Hidroxicloroquina , Betacoronavirus/isolamento & purificação , China , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/uso terapêutico , Pandemias , Projetos Piloto , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/tratamento farmacológico , RNA Viral/isolamento & purificação , Resultado do Tratamento
9.
Ugeskr Laeger ; 182(20)2020 05 11.
Artigo em Dinamarquês | MEDLINE | ID: mdl-32400380

RESUMO

The severity of COVID-19 disease has led to an urgent need for the discovery of new treatments. Thus, global stocks of hydroxychloroquine (HCQ) have been put under pressure with a study of 26 patients treated with HCQ during their infection with SARS-CoV-2. Despite the study's lack of quality, several countries' medicines agencies subsequently issued guidelines for the use of HCQ for COVID-19. This review aims to elucidate potential mechanisms, which make HCQ treatment interesting in the fight against SARS-CoV-2 infection, as well as the current evidence for clinical use of HCQ to treat COVID-19.


Assuntos
Antivirais , Infecções por Coronavirus , Hidroxicloroquina , Pandemias , Pneumonia Viral , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico
11.
Eur Rev Med Pharmacol Sci ; 24(8): 4539-4547, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32373993

RESUMO

OBJECTIVE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS: We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on "COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS: For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS: Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis.


Assuntos
Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Ensaios Clínicos como Assunto , Humanos , Pandemias
13.
BMJ ; 369: m1844, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409486

RESUMO

OBJECTIVE: To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen. DESIGN: Comparative observational study using data collected from routine care. SETTING: Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020. PARTICIPANTS: 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care. INTERVENTIONS: Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group). MAIN OUTCOME MEASURES: The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting. RESULTS: In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment. CONCLUSIONS: Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Adulto Jovem
14.
BMJ ; 369: m1849, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409561

RESUMO

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Resultado do Tratamento
16.
Diabetes Metab Syndr ; 14(3): 241-246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247211

RESUMO

BACKGROUND AND AIMS: No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried. In view of recent studies and discussion on chloroquine and hydroxychloroquine (HCQ), we aimed to review existing literature and relevant websites regarding these drugs and COVID-19, adverse effects related to drugs, and related guidelines. AIMS AND METHODS: We systematically searched the PubMed database up till March 21, 2020 and retrieved all the articles published on chloroquine and HCQ and COVID-19. RESULTS: Two small human studies have been conducted with both these drugs in COVID-19, and have shown significant improvement in some parameters in patients with COVID-19. CONCLUSION: Considering minimal risk upon use, a long experience of use in other diseases, cost-effectiveness and easy availability across India, we propose that both these drugs are worthy of fast track clinical trial for treatment, and may be carefully considered for clinical use as experimental drugs. Since HCQ has been approved for treatment of diabetes in India, it should be further researched in diabetes and COVID-19, a subgroup where significant mortality has been shown.


Assuntos
Betacoronavirus/efeitos dos fármacos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Diabetes Mellitus , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/complicações , Países em Desenvolvimento , Complicações do Diabetes , Humanos , Índia , Pandemias , Pneumonia Viral/complicações
19.
Pediatr Rheumatol Online J ; 18(1): 35, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321540

RESUMO

On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities.In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure.Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs.


Assuntos
Antirreumáticos/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pediatras , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Doenças Reumáticas/complicações , Doenças Reumáticas/virologia , Reumatologistas , Adolescente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Juvenil/complicações , Artrite Juvenil/virologia , Betacoronavirus , Criança , Pré-Escolar , Cloroquina/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Humanos , Hidroxicloroquina/uso terapêutico , Lactente , Interleucina-6/antagonistas & inibidores , Itália/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia
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