Retraction of Clinical Trials about the SARS-CoV-2 Infection: An Unaddressed Problem and Its Possible Impact on Coronavirus Disease (COVID)-19 Treatment.

We are presenting an overview of the retracted clinical trials about the Coronavirus Disease (COVID)-19 published in PubMed using the descriptors ((COVID-19 OR SARS-CoV-2) AND (Clinical Trial)). We collected the information for i) the first author's country; ii) the journal name where the study was published; iii) the impact factor of the journal; iv) the main objective of the study; v) methods including population, intervention, study design, and outcomes; and vi) results and conclusions. We collected complete information from the retraction notes published by the journals and the number of publications/retractions related to non-COVID-19 clinical trials published simultaneously. We also included the Altmetric index for the clinical trials and the retraction notes about COVID-19 to compare the accessibility to both studies' indexes. The retraction of clinical trials occurred in four countries (one in Lebanon, one in India, one in Brazil, and five in Egypt) and six journals (one in Viruses, one in Archives of Virology, one in Expert Review of Anti-infective Therapy, one in Frontiers in Medicine, two in Scientific Reports, and two in The American Journal of Tropical Medicine and Hygiene). Eight drugs were tested (Ivermectin, Vitamin D, Proxalutamide, Hydroxychloroquine, Remdesevir, Favipiravir, and Sofosbuvir + Daclatasvir) in the studies. One of the retractions was suggested by the authors due to an error in the statistical analysis, which compromised their results and conclusions. Also, the methods, mainly the allocation, were not well conducted in the two studies, and the studies were retracted. In addition, the studies performed by Dabbous et al. presented several issues, mainly including several raw datasets that did not prove their findings. Moreover, two studies were retracted due to data overlap and copying. Significant concerns were raised about the integrity of the data and reported results in another article. We identified a higher Altmetric index for the original studies, proving that the retracted studies were accessed more than the retraction notes. Interestingly, the impact of the original articles is much higher than their retraction notes. The different Altmetric indexes show that possibly people who read those retracted articles are not reading their retraction notes and are unaware of the erroneous information they share. COVID-19- related clinical trials were ~two-time times more retracted than the other clinical trials performed during the same time.

Profile of coronavirus disease enlightened asthma as a protective factor against death: An epidemiology study from Brazil during the pandemic.

Introduction: The possibility that asthma is not a risk factor for the worst outcomes due to coronavirus disease (COVID-19) is encouraged. The increase in Th2 response dominance can downregulate the late phase of hyperinflammation, which is typically the hallmark of more severe respiratory viral infections, alongside lower angiotensin-converting enzyme receptors in patients with asthma due to chronic inflammation. Few studies associated asthma diagnosis and COVID-19 outcomes. In this context, we aimed to associate the asthma phenotype with the clinical signs, disease progression, and outcomes in patients with COVID-19. Methods: We performed an epidemiologic study using patients' characteristics from OpenDataSUS to verify the severity of COVID-19 among Brazilian hospitalized patients with and without the asthma phenotype according to the need for intensive care units, intubation, and deaths. We also evaluated the demographic data (sex, age, place of residence, educational level, and race), the profile of clinical signs, and the comorbidities. Results: Asthma was present in 43,245/1,129,838 (3.8%) patients. Among the patients with asthma, 74.7% who required invasive ventilatory support evolved to death. In contrast, 78.0% of non-asthmatic patients who required invasive ventilatory support died (OR = 0.83; 95% CI = 0.79-0.88). Also, 20.0% of the patients with asthma that required non-invasive ventilatory support evolved to death, while 23.5% of non-asthmatic patients evolved to death (OR = 0.81; 95% CI = 0.79-0.84). Finally, only 11.2% of the patients with asthma who did not require any ventilatory support evolved to death, while 15.8% of non-asthmatic patients evolved to death (OR = 0.67; 95% CI = 0.62-0.72). In our multivariate analysis, one comorbidity and one clinical characteristic stood out as protective factors against death during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with asthma were less prone to die than other patients (OR = 0.79; 95% CI = 0.73-0.85), just like puerperal patients (OR = 0.74; 95% CI = 0.56-0.97) compared to other patients. Conclusion: Asthma was a protective factor for death in hospitalized patients with COVID-19 in Brazil. Despite the study's limitations on patients' asthma phenotype information and corticosteroid usage, this study brings to light information regarding a prevalent condition that was considered a risk factor for death in COVID-19, being ultimately protective.

Characterization of Clinical Features of Hospitalized Patients Due to the SARS-CoV-2 Infection in the Absence of Comorbidities Regarding the Sex: An Epidemiological Study of the First Year of the Pandemic in Brazil.

The male sex, due to the presence of genetic, immunological, hormonal, social, and environmental factors, is associated with higher severity and death in Coronavirus Disease (COVID)-19. We conducted an epidemiological study to characterize the COVID-19 clinical profile, severity, and outcome according to sex in patients with the severe acute respiratory syndrome (SARS) due to the fact of this disease. We carried out an epidemiological analysis using epidemiological data made available by the OpenDataSUS, which stores information about SARS in Brazil. We recorded the features of the patients admitted to the hospital for SARS treatment due to the presence of COVID-19 (in the absence of comorbidities) and associated these characteristics with sex and risk of death. The study comprised 336,463 patients, 213,151 of whom were men. Male patients presented a higher number of clinical signs, for example, fever (OR = 1.424; 95%CI = 1.399−1.448), peripheral arterial oxygen saturation (SpO2) < 95% (OR = 1.253; 95%CI = 1.232−1.274), and dyspnea (OR = 1.146; 95%CI = 1.125−1.166) as well as greater need for admission in intensive care unit (ICU, OR = 1.189; 95%CI = 1.168−1.210), and the use of invasive ventilatory support (OR = 1.306; 95%CI = 1.273−1.339) and noninvasive ventilatory support (OR = 1.238; 95%CI = 1.216−1.260) when compared with female patients. Curiously, the male sex was associated only with a small increase in the risk of death when compared with the female sex (OR = 1.041; 95%CI = 1.023−1.060). We did a secondary analysis to identify the main predictors of death. In that sense, the multivariate analysis enabled the prediction of the risk of death, and the male sex was one of the predictors (OR = 1.101; 95%CI = 1.011−1.199); however, with a small effect size. In addition, other factors also contributed to this prediction and presented a great effect size, they are listed below: older age (61−72 years old (OR = 15.778; 95%CI = 1.865−133.492), 73−85 years old (OR = 31.978; 95%CI = 3.779−270.600), and +85 years old (OR = 68.385; 95%CI = 8.164−589.705)); race (Black (OR = 1.247; 95%CI = 1.016−1.531), Pardos (multiracial background; OR = 1.585; 95%CI = 1.450−1.732), and Indigenous (OR = 3.186; 95%CI = 1.927−5.266)); clinical signs (for instance, dyspnea (OR = 1.231; 95%CI = 1.110−1.365) and SpO2 < 95% (OR = 1.367; 95%CI = 1.238−1.508)); need for admission in the ICU (OR = 3.069; 95%CI = 2.789−3.377); and for ventilatory support (invasive (OR = 10.174; 95%CI = 8.803−11.759) and noninvasive (OR = 1.609; 95%CI = 1.438−1.800)). In conclusion, in Brazil, male patients tend to present the phenotype of higher severity in COVID-19, however, with a small effect on the risk of death.

Human Development Index Is Associated with COVID-19 Case Fatality Rate in Brazil: An Ecological Study.

The Human Development Index measures a region's development and is a step for development debate beyond the traditional, economic perspective. It can also determine the success of a country's response to the COVID-19 pandemic, mainly affecting the case fatality rate among severe cases of SARS-CoV-2 infection. We aimed to associate the Human Development Index with the case fatality rate due to COVID-19 in each Brazilian state and the Federal District, taking into account comorbidities and the need for invasive mechanical ventilation. We also evaluated the influence of the GINI index, number of intensive care unit beds, and occupied households in subnormal clusters on the case fatality rate. We performed an ecological study including two populations: COVID-19 individuals that did not require the mechanical ventilation protocol; and COVID-19 individuals under invasive mechanical ventilation. We performed a Pearson correlation test and a univariate linear regression analysis on the relationship between Human Development Index, Human Development Index-Education Level, Human Development Index-Life Expectancy, and Human Development Index-Gross National Income per capita and COVID-19 deaths. The same analyses were performed using the other markers. We grouped the patients with COVID-19 according to comorbidities and the need for invasive mechanical ventilation. Alpha = 0.05. We included 848,501 COVID-19 individuals, out of which 153,710 needed invasive mechanical ventilation and 314,164 died, and 280,533 COVID-19 individuals without comorbidity, out of which 33,312 needed invasive mechanical ventilation and 73,723 died. We observed a low negative Pearson correlation between the Human Development Index and death and a moderate negative Pearson correlation between the Human Development Index and deaths of individuals on invasive mechanical ventilation, with or without comorbidity. The univariate linear analysis showed the case fatality rate depends on at least 20-40% of the Human Development Index. In Brazil, regions with a low Human Development Index demonstrated a higher case fatality rate due to COVID-19, mainly in individuals who needed invasive mechanical ventilation, than regions with a higher Human Development Index. Although other indexes studied, such as intensive care unit beds and GINI, were also associated with the COVID-19 case fatality rate, they were not as relevant as the Human Development Index. Brazil is a vast territory comprising cultural, social, and economic diversity, which mirrors the diversity of the Human Development Index. Brazil is a model nation for the study of the Human Development Index's influence on aspects of the COVID-19 pandemic, such as its impact on the case fatality rate.

Opioids in COVID-19: Two Sides of a Coin.

Introduction: The treatment of most severe COVID-19 patients included the large-scale use of sedatives and analgesics-possibly in higher doses than usual-which was reported in the literature. The use of drugs that decrease mortality is necessary and opioids are important agents in procedures such as orotracheal intubation. However, these drugs seem to have been overestimated in the COVID-19 pandemic. We performed a review of the PubMed-Medline database to evaluate the use of opioids during this period. The following descriptors were used to enhance the search for papers: "Opioids", "COVID-19," "COVID-19 pandemic," "SARS-CoV-2," "Opioid use disorder," "Opioid dependence" and the names of the drugs used. We also evaluated the distribution of COVID-19 patients in Brazil and the applicability of opioids in our country during the COVID-19 pandemic. Results: Several positive points were found in the use of opioids in the COVID-19 pandemic, for instance, they can be used for analgesia in orotracheal intubation, for chronic pain management, and as coadjutant in the management of acute intensification of pain. However, high doses of opioids might exacerbate the respiratory depression found in COVID-19 patients, their chronic use can trigger opioid tolerance and the higher doses used during the pandemic might result in greater adverse effects. Unfortunately, the pandemic also affected individuals with opioid use disorder, not only those individuals are at higher risk of mortality, hospitalization and need for ventilatory support, but measures taken to decrease the SARS-CoV-2 spread such as social isolation, might negatively affect the treatment for opioid use disorder. In Brazil, only morphine, remifentanil and fentanyl are available in the basic health care system for the treatment of COVID-19 patients. Out of the 5,273,598 opioid units used in this period all over the country, morphine, fentanyl, and remifentanil, accounted for, respectively, 559,270 (10.6%), 4,624,328 (87.6%), and 90,000 (1.8%) units. Many Brazilian regions with high number of confirmed cases of COVID-19 had few units of opioids available, as the Southeast region, with a 0.23 units of opioids per confirmed COVID-19 case, and the South region, with 0.05 units. In the COVID-19 pandemic scenario, positive points related to opioids were mainly the occurrence of analgesia, to facilitate intubation and their use as coadjutants in the management of acute intensification of pain, whereas the negative points were indiscriminate use, the presence of human immunosuppressor response and increased adverse effects due to higher doses of the drug. Conclusion: The importance of rational and individualized use of analgesic hypnotics and sedative anesthetics should be considered at all times, especially in situations of high demand such as the COVID-19 pandemic.