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Objectives: To compare the number of suspected cases, severe cases, and deaths of dengue in 2023 and 2024 in Brazil and Latin America; and to describe its epidemiological profile., Design: Observational study., Methods: The data regarding dengue was retrieved from the Brazilian Ministry of Health website. The Chi-square test was used to compare the proportion of dengue cases in 2023 and 2024 according to gender, race, and age range. The odds ratio and the 95% confidence intervals were used to describe the data. The Spearman correlation test was used to compare the number of suspected cases, severe cases, and deaths of dengue with the number of distributed vaccines against dengue., Results: Dengue is one of the most common zoonoses in Latin America. In 2023, Brazil registered a total of 1,658,814 suspected cases of dengue with 1094 deaths. For 2024, a total of 1,978,372 suspected cases of dengue were reported only until the 11th epidemiological week, with 656 deaths. When comparing dengue cases reported in 2024 and 2023, there is an increase in suspected cases, with 20% more cases reported during the first 11 epidemiological weeks of 2024 than in the entire 52 epidemiological weeks of 2023. At the same time, in 2024, the Pan American Health Organization reported suspected cases in 20 Latin American countries, with 3073 cases of severe dengue and 1187 deaths. In Brazil, a different racial profile for dengue was described since Black people [OR = 1.56 (95% CI = 1.54-1.57)], Mixed individuals [OR = 1.36 (95% CI = 1.35-1.37), and Indigenous peoples [OR = 1.77 (95% CI = 1.70-1.85)] were more likely to be suspected cases of dengue in 2024 compared to 2023. Also, a positive correlation between the distributed vaccines with deaths due to dengue and the number of severe cases was described., Conclusion: Brazil was responsible for more than 50% of suspected cases and deaths from dengue compared to the other Latin American countries in 2024. Furthermore, there is a different racial profile for dengue in Brazil, as Black people, Mixed individuals, and Indigenous peoples were more likely to be suspected cases of dengue in 2024 compared to 2023., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: During the coronavirus disease (COVID)-19 pandemic several drugs were used to manage the patients mainly those with a severe phenotype. Potential drugs were used off-label and major concerns arose from their applicability to managing the health crisis highlighting the importance of clinical trials. In this context, we described the mechanisms of the three repurposed drugs [Ivermectin-antiparasitic drug, Chloroquine/Hydroxychloroquine-antimalarial drugs, and Azithromycin-antimicrobial drug]; and, based on this description, the study evaluated the clinical efficacy of those drugs published in clinical trials. The use of these drugs reflects the period of uncertainty that marked the beginning of the COVID-19 pandemic, which made them a possible treatment for COVID-19. Methods: In our review, we evaluated phase III randomized controlled clinical trials (RCTs) that analyzed the efficacy of these drugs published from the COVID-19 pandemic onset to 2023. We included eight RCTs published for Ivermectin, 11 RCTs for Chloroquine/Hydroxychloroquine, and three RCTs for Azithromycin. The research question (PICOT) accounted for P-hospitalized patients with confirmed or suspected COVID-19; I-use of oral or intravenous Ivermectin OR Chloroquine/Hydroxychloroquine OR Azithromycin; C-placebo or no placebo (standard of care); O-mortality OR hospitalization OR viral clearance OR need for mechanical ventilation OR clinical improvement; and T-phase III RCTs. Results: While studying these drugs' respective mechanisms of action, the reasons for which they were thought to be useful became apparent and are as follows: Ivermectin binds to insulin-like growth factor and prevents nuclear transportation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), therefore preventing cell entrance, induces apoptosis, and osmotic cell death and disrupts viral replication. Chloroquine/Hydroxychloroquine blocks the movement of SARS-CoV-2 from early endosomes to lysosomes inside the cell, also, this drug blocks the binding between SARS-CoV-2 and Angiotensin-Converting Enzyme (ACE)-2 inhibiting the interaction between the virus spike proteins and the cell membrane and this drug can also inhibit SARS-CoV-2 viral replication causing, ultimately, the reduction in viral infection as well as the potential to progression for a higher severity phenotype culminating with a higher chance of death. Azithromycin exerts a down-regulating effect on the inflammatory cascade, attenuating the excessive production of cytokines and inducing phagocytic activity, and acts interfering with the viral replication cycle. Ivermectin, when compared to standard care or placebo, did not reduce the disease severity, need for mechanical ventilation, need for intensive care unit, or in-hospital mortality. Only one study demonstrated that Ivermectin may improve viral clearance compared to placebo. Individuals who received Chloroquine/Hydroxychloroquine did not present a lower incidence of death, improved clinical status, or higher chance of respiratory deterioration compared to those who received usual care or placebo. Also, some studies demonstrated that Chloroquine/Hydroxychloroquine resulted in worse outcomes and side-effects included severe ones. Adding Azithromycin to a standard of care did not result in clinical improvement in hospitalized COVID-19 participants. In brief, COVID-19 was one of the deadliest pandemics in modern human history. Due to the potential health catastrophe caused by SARS-CoV-2, a global effort was made to evaluate treatments for COVID-19 to attenuate its impact on the human species. Unfortunately, several countries prematurely justified the emergency use of drugs that showed only in vitro effects against SARS-CoV-2, with a dearth of evidence supporting efficacy in humans. In this context, we reviewed the mechanisms of several drugs proposed to treat COVID-19, including Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin, as well as the phase III clinical trials that evaluated the efficacy of these drugs for treating patients with this respiratory disease. Conclusions: As the main finding, although Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin might have mechanistic effects against SARS-CoV-2 infection, most phase III clinical trials observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials.

Since the onset of the coronavirus disease, COVID-19 pandemic, concern arose for those who might be at higher risk of a worse COVID-19 prognosis, such as those with cystic fibrosis (CF). In this context, we evaluated the features of hospitalized patients with CF due to severe acute respiratory infection (SARI) in Brazil and we also performed a systematic review including all the studies published from the beginning of the first case of COVID-19 (17 November 2019) to the date of this search (23 May 2022) which included, concomitantly, patients with CF and COVID-19 in the worldwide population. In our Brazilian data, we evaluated the period from December 2019 to March 2022, and we included 33 demographical and clinical patients' features. We classified the patients into groups: (G1) SARI due to another viral infection than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (23; 5.4%), (G2) SARI due to an unknown etiological agent (286; 67.1%), and (G3) SARI due to SARS-CoV-2 infection (117; 27.5%). The individuals in G3 tended to be older, especially over 50 years old, and presented a higher prevalence of dyspnea, peripheral capillary oxygen saturation (SpO 2 ) <95%, and cardiopathy. The highest prevalence for intensive care unit (ICU) treatment (52; 44.4%) and invasive mechanical ventilation (29; 24.8%) was for patients in G3. Almost half of the patients in G3 died (51; 43.6%); in contrast, none in G1 died. However, we observed 43 (15.0%) deaths in G2. In addition, 12 (4.2%) and one (0.9%) death not associated with SARI occurred, respectively, in the G2 and G3. The patients who died due to SARS-CoV-2 infection had a higher frequency of SpO 2 <95% (46; 90.2%), ICU treatment (34; 66.7%), and invasive mechanical ventilation (27; 52.9%) when compared to those who recovered. The systematic review comprised a total of 31 papers published as observational studies. These studies comprised 661,386 patients in total, including children, adults, and elderly age groups. However, only 19,150 (2.9%) patients were diagnosed with CF and, from these patients, 2523 (0.4%) were diagnosed with both CF and COVID-19. It was observed that the most common outcome was the need for hospitalization (n = 322 patients with CF), and the need for oxygen support (n = 139 patients with CF). One hundred patients with CF needed intensive care units, fifty patients needed non-invasive mechanical ventilation support, and only three patients were described as receiving invasive mechanical ventilation support. Deaths were described in 38 patients with CF. Importantly, lung-transplanted patients with CF represented an increased risk of death in one publication; in accordance, another study described that lung transplantation and moderate to severe lung disease were independent risk factors for severe outcomes after SARS-CoV-2 infection. In contrast with the literature, in conclusion, Brazilian patients in G3 presented a severe phenotype, even though most of the other studies did not observe worse outcomes in patients with CF and COVID-19.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sansone, Valencise, Bredariol, Peixoto and Marson.)

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.

Background: The COVID-19 is a significant public health issue, and monitoring confirmed cases and deaths is an essential epidemiologic tool. We evaluated the features in Brazilian hospitalized patients due to severe acute respiratory infection (SARI) during the COVID-19 pandemic in Brazil. We grouped the patients into the following categories: Influenza virus infection (G1), other respiratory viruses' infection (G2), other known etiologic agents (G3), SARS-CoV-2 infection (patients with COVID-19, G4), and undefined etiological agent (G5)., Methods: We performed an epidemiological study using data from DataSUS (https://opendatasus.saude.gov.br/) from December 2019 to October 2021. The dataset included Brazilian hospitalized patients due to SARI. We considered the clinical evolution of the patients with SARI during the COVID-19 pandemic according to the SARI patient groups as the outcome. We performed the multivariate statistical analysis using logistic regression, and we adopted an Alpha error of 0.05., Results: A total of 2,740,272 patients were hospitalized due to SARI in Brazil, being the São Paulo state responsible for most of the cases [802,367 (29.3%)]. Most of the patients were male (1,495,416; 54.6%), aged between 25 and 60 years (1,269,398; 46.3%), and were White (1,105,123; 49.8%). A total of 1,577,279 (68.3%) patients recovered from SARI, whereas 701,607 (30.4%) died due to SARI, and 30,551 (1.3%) did not have their deaths related to SARI. A major part of the patients was grouped in G4 (1,817,098; 66.3%) and G5 (896,207; 32.7%). The other groups account for <1% of our sample [G1: 3,474 (0.1%), G2: 16,627 (0.6%), and G3: 6,866 (0.3%)]. The deaths related to SARI were more frequent in G4 (574,887; 34.7%); however, the deaths not related to SARI were more frequent among the patients categorized into the G3 (1,339; 21.3%) and G5 (25,829; 4.1%). In the multivariate analysis, the main predictors to classify the patients in the G5 when compared with G4 or G1-G4 were female sex, younger age, Black race, low educational level, rural place of residence, and the use of antiviral to treat the clinical signs. Furthermore, several features predict the risk of death by SARI, such as older age, race (Black, Indigenous, and multiracial background), low educational level, residence in a flu outbreak region, need for intensive care unit, and need for mechanical ventilatory support., Conclusions: The possible COVID-19 underreporting (G5) might be associated with an enhanced mortality rate, more evident in distinct social groups. In addition, the patients' features are unequal between the patients' groups and can be used to determine the risk of possible COVID-19 underreporting in our population. Patients with a higher risk of death had a different epidemiological profile when compared with patients who recovered from SARI, like older age, Black, Indigenous, and multiracial background races, low educational level, residence in a flu outbreak region, need for intensive care unit and need for mechanical ventilatory support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sansone, Boschiero and Marson.)

Background: Indigenous peoples are vulnerable to pandemics, including to the coronavirus disease (COVID)-19, since it causes high mortality and specially, the loss of elderly Indigenous individuals., Methods: The epidemiological data of severe acute respiratory syndrome (SARS) by SARS-CoV-2 infection or other etiologic agents (OEA) among Brazilian Indigenous peoples during the first year of COVID-19 pandemic was obtained from a Brazilian Ministry of Health open-access database to perform an observational study. Considering only Indigenous individuals diagnosed with SARS by COVID-19, the epidemiology data were also evaluated as risk of death. The type of sample collection for virus screening, demographic profile, clinical symptoms, comorbidities, and clinical evolution were evaluated. The primary outcome was considered the death in the Brazilian Indigenous individuals and the secondary outcome, the characteristics of Brazilian Indigenous infected by SARS-CoV-2 or OEA, as the need for intensive care unit admission or the need for mechanical ventilation support. The statistical analysis was done using Logistic Regression Model. Alpha of 0.05., Findings: A total of 3,122 cases of Indigenous individuals with SARS in Brazil were reported during the first year of the COVID-19 pandemic. Of these, 1,994 were diagnosed with COVID-19 and 730/1,816 (40.2%) of them died. The death rate among individuals with SARS-CoV-2 was three-fold increased when compared to the group of individuals with OEA. Several symptoms (myalgia, loss of smell, and sore throat) and comorbidities (cardiopathy, systemic arterial hypertension, and diabetes mellitus) were more prevalent in the COVID-19 group when compared to Indigenous individuals with OEA. Similar profile was observed considering the risk of death among the Indigenous individuals with COVID-19 who presented several symptoms (oxygen saturation <95%, dyspnea, and respiratory distress) and comorbidities (renal disorders, cardiopathy, and diabetes mellitus). The multivariate analysis was significant in differentiating between the COVID-19-positive and non-COVID-19 patients [X 2 (7) =65.187; P-value<0.001]. Among the patients' features, the following contributed in relation to the diagnosis of COVID-19: age [≥43 years-old [y.o.]; OR=1.984 (95%CI=1.480-2.658)]; loss of smell [OR=2.373 (95%CI=1.461-3.854)]; presence of previous respiratory disorders [OR=0.487; 95%CI=0.287-0.824)]; and fever [OR=1.445 (95%CI=1.082-1.929)]. Also, the multivariate analysis was able to predict the risk of death [X 2 (9) =293.694; P-value<0.001]. Among the patients' features, the following contributed in relation to the risk of death: male gender [OR=1.507 (95%CI=1.010-2.250)]; age [≥60 y.o.; OR=3.377 (95%CI=2.292-4.974)]; the need for ventilatory support [invasive mechanical ventilation; OR=24.050 (95%CI=12.584-45.962) and non-invasive mechanical ventilation; OR=2.249 (95%CI=1.378-3.671)]; dyspnea [OR=2.053 (95%CI=1.196-3.522)]; oxygen saturation <95% [OR=1.691 (95%CI=1.050-2.723)]; myalgia [OR=0.423 (95%CI=0.191-0.937)]; and the presence of kidney disorders [OR=3.135 (95%CI=1.144-8.539)]., Interpretation: The Brazilian Indigenous peoples are in a vulnerable situation during the COVID-19 pandemic and presented an increased risk of death due to COVID-19. Several factors were associated with enhanced risk of death, as male sex, older age (≥60 y.o.), and need for ventilatory support; also, other factors might help to differentiate SARS by COVID-19 or by OEA, as older age (≥43 y.o.), loss of smell, and fever., Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (Foundation for Research Support of the State of São Paulo; #2021/05810-7)., Competing Interests: None., (© 2021 The Author(s).)