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      What happens in Brazil? A pandemic of misinformation that culminates in an endless disease burden

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          Brazil is currently one of the main centers of the coronavirus disease 2019 (COVID-19) pandemic. Despite the low testing rates, recent epidemiological data estimates more than 5.8 million cases and more than 165.000 cumulative deaths in the country; an alarming number. The pandemic follows an uncontrolled rhythm, with insufficient sanitary rules and inadequate orientation for the population, which is not completely aware of the threats of the pandemic. The inefficient official communication, which is not based on scientific evidence, also contributes to the spread of the disease in Brazil. In addition, the different levels of population incomes create clear discrepancies, leading to early access to medical support services for high-net-worth subjects, giving them a definite advantage. Furthermore, the nutritional status of the population is also highly influenced by education and purchasing power; therefore, obesity is an important comorbidity predominant among underprivileged Brazilians 1 . Apart from these discrepancies, Brazil is a fertile field for misinformation that hinders adequate measures taken to mitigate COVID-19. For example, chloroquine/hydroxychloroquine and ivermectin, which have not been proven to be clinically efficient for COVID-19 2 , 3 , are widely distributed as miracle pills to constrain virus transmission at the expense of protective measures. Hydroxychloroquine may also inhibit antibody responses to vaccines and, in addition to its highly undesirable effects in the clinical-epidemiological setting of COVID-19, its indiscriminate use could impact the studies investigating immunity to this virus as well as vaccine testing 4 . In spite of this, hydroxychloroquine is still being peddled by some health professionals under pressure from politicians and government authorities. Ivermectin is another controversial drug that is being used not only to treat but also to prevent COVID-19 in Brazil, despite lack of any confirmation of its effect on clinical outcomes 5 . The use of ivermectin (and, for that matter, antibiotics) may also hinder immunity to the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 because they can modify the user's intestinal microbiota 6 and thus impact their ability to mount effective responses to several vaccines 7 , 8 . It is reasonable to expect that ivermectin and antibiotics, in general, will also affect immunity to SARS-CoV-2, especially in those who employ ivermectin prophylactically, as occurs in Brazil. Therefore, the consequences of this widespread self-medication for COVID-19 could potentially contribute to the infection spreading and long-term prevalence of the epidemic in this country. The consequences of such improper approaches for mitigating COVID-19 are worrying, leading to illusionary feelings of immunity to the virus, which underlie misguided behaviors such as not using masks and not observing social distancing by people for whom taking these medicines is the panacea for the pandemic's control. Indeed, social isolation, especially the lockdown, is a fundamental measure to control the virus spread 9 . Otherwise, the recent premature reopening of non-essential services in Brazil may further increase the rate of COVID-19 spread in the country 10 . Considering face masks, further reasons for encouraging their use are the issue recently raised by Gandhi and Rutherford regarding their potential for promoting "variolization" in individuals. This concept must be taught to the lay population in order to increase adherence 11 . Understanding the determinants by which people resist adopting protective measures is clearly of great importance so that public policies based on social isolation could have their desired effects - avoiding or reducing non-adherence to control measures. Regarding the Health Belief Model (HBM) 12 and COVID-19 in Brazil, low income is an important factor, which must be seen in a comprehensive way, since it is associated with the reduced quantity and quality of disseminated information, housing conditions that favor contamination, and difficulty in interrupting daily activities for economic reasons 13 , as recently raised by Silva an Arbilla (2020) in the recent discussion about the new "Human Epoch" 14 . Furthermore, even though many are worried about the likelihood of getting COVID-19, relatively few viewed themselves as being at high risk of becoming infected with SARS-CoV-2. Although some initial controlling measures aimed to constrain the spreading of COVID-19 in Brazil 15 , the consecutive political divergences may also have contributed to a lack of compliance toward protective measures by the population. In addition, following their leaders' behaviors and refusing to wear face masks is being regarded by some citizens as a means of making their political positions known. This indicates the need to increase risk perception among the public, as it can translate into preventive actions and enhance epidemic control. Thus, interventions targeting HBM dimensions could be an alternative in an attempt to control COVID-19 dissemination in Brazil. Moreover, we should be able to identify the agnotological strategies in order to have a more efficient response against the pandemic, which should be mainly based on scientific evidences 16 . Finally, in view of this unique mixture of social, economic, and cultural behaviors, the main questions that remain are what is the future of COVID-19 in Brazil and when or how it will be controlled, including adherence to vaccination when it becomes available. Considering the magnitude of the spread of the disease in such a large and diverse country, the epidemic in Brazil could lead to serious consequences inside as well as outside its borders and thus impact the adequate control of the pandemic, including vaccine efficiency.

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          Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

          Abstract Background Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. Methods We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. Results Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. Conclusions In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)
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            The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro

            Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 able to effect ∼5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
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              Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State

              Among patients with coronavirus disease 2019 (COVID-19), is there an association between use of hydroxychloroquine, with or without azithromycin, and in-hospital mortality? In a retrospective cohort study of 1438 patients hospitalized in metropolitan New York, compared with treatment with neither drug, the adjusted hazard ratio for in-hospital mortality for treatment with hydroxychloroquine alone was 1.08, for azithromycin alone was 0.56, and for combined hydroxychloroquine and azithromycin was 1.35. None of these hazard ratios were statistically significant. Among patients hospitalized with COVID-19, treatment with hydroxychloroquine, azithromycin, or both was not associated with significantly lower in-hospital mortality. Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events. To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19. Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020. Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither. Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation). Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O 2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings. Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design. This study examines associations between use of hydroxychloroquine, azithromycin, or both and in-hospital mortality, ECG changes, and cardiac arrest among patients with COVID-19 hospitalized in the metropolitan New York area in March 2020.

                Author and article information

                Rev Soc Bras Med Trop
                Rev Soc Bras Med Trop
                Revista da Sociedade Brasileira de Medicina Tropical
                Sociedade Brasileira de Medicina Tropical - SBMT
                21 December 2020
                : 54
                [1 ] Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Ribeirão Preto, SP, Brasil.
                [2 ] Universidade de São Paulo, Escola de Enfermagem de Ribeirão Preto, Departamento de Enfermagem Geral e Especializada, Ribeirão Preto, SP, Brasil.
                [3 ] Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Bioquímica e Imunologia, Ribeirão Preto, SP, Brasil.
                Author notes
                Corresponding author: Dr. Cristina Ribeiro de Barros Cardoso. e-mail: cristina@ 123456fcfrp.usp.br

                Authors’ contribution: CRBC: Conception and design of the study, acquisition of data, analysis and interpretation of data, drafting of the article, final approval of the version to be submitted; APMF: Acquisition of data, analysis and interpretation of data, drafting of the article, final approval of the version to be submitted; IKMS: Conception and design of the study, acquisition of data, analysis and interpretation of data, final approval of the version to be submitted.

                Conflict of Interest: The authors declare that there is no conflict of interest.


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