Correlating drug prescriptions with prognosis in severe COVID-19: first step towards resource management.

BACKGROUND: Optimal COVID-19 management is still undefined. In this complicated scenario, the construction of a computational model capable of extracting information from electronic medical records, correlating signs, symptoms and medical prescriptions, could improve patient management/prognosis. METHODS: The aim of this study is to investigate the correlation between drug prescriptions and outcome in patients with COVID-19. We extracted data from 3674 medical records of hospitalized patients: drug prescriptions, outcome, and demographics. The outcome evaluated was hospital outcome. We applied correlation analysis using a Logistic Regression algorithm for machine learning with Lasso and Matthews correlation coefficient. RESULTS: We found correlations between drugs and patient outcomes (death/discharged alive). Anticoagulants, used very frequently during all phases of the disease, were associated with good prognosis only after the first week of symptoms. Antibiotics very frequently prescribed, especially early, were not correlated with outcome, suggesting that bacterial infections may not be important in determining prognosis. There were no differences between age groups. CONCLUSIONS: In conclusion, we achieved an important result in the area of Artificial Intelligence, as we were able to establish a correlation between concrete variables in a real and extremely complex environment of clinical data from COVID-19. Our results are an initial and promising contribution in decision-making and real-time environments to support resource management and forecasting prognosis of patients with COVID-19.

Covid-19 Automated Diagnosis and Risk Assessment through Metabolomics and Machine Learning.

COVID-19 is still placing a heavy health and financial burden worldwide. Impairment in patient screening and risk management plays a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study enrolled 815 patients (442 COVID-19, 350 controls and 23 COVID-19 suspicious) from three Brazilian epicenters from April to July 2020. We were able to elect and identify 19 molecules related to the disease's pathophysiology and several discriminating features to patient's health-related outcomes. The method applied for COVID-19 diagnosis showed specificity >96% and sensitivity >83%, and specificity >80% and sensitivity >85% during risk assessment, both from blinded data. Our method introduced a new approach for COVID-19 screening, providing the indirect detection of infection through metabolites and contextualizing the findings with the disease's pathophysiology. The pairwise analysis of biomarkers brought robustness to the model developed using machine learning algorithms, transforming this screening approach in a tool with great potential for real-world application.

The Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Left-sided Endocarditis: Native vs Prosthetic Valves Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has emerged as a useful diagnostic tool for suspected infective endocarditis (IE) in patients with prosthetic valves or implantable devices. However, there is limited evidence regarding use of 18F-FDG-PET/CT for the diagnosis of native valve endocarditis (NVE). METHODS: Between 2014 and 2017, 303 episodes of left-sided suspected IE (188 prosthetic valves/ascending aortic prosthesis and 115 native valves) were studied. 18F-FDG-PET/CT accuracy was determined in the subgroups of patients with NVE and prosthetic valve endocarditis (PVE)/ascending aortic prosthesis infection (AAPI). Associations between inflammatory infiltrate patterns and 18F-FDG-PET/CT uptake were investigated in an exploratory ad hoc histological analysis. RESULTS: Among 188 patients with PVE/AAPI, the sensitivity, specificity, and positive and negative predictive values of 18F-FDG-PET/CT focal uptake were 93%, 90%, 89%, and 94%, respectively, while among 115 patients with NVE, the corresponding values were 22%, 100%, 100%, and 66%. The inclusion of abnormal 18F-FDG cardiac uptake as a major criterion at admission enabled a recategorization of 76% (47/62) of PVE/AAPI cases initially classified as "possible" to "definite" IE. In the histopathological analysis, a predominance of polymorphonuclear cell inflammatory infiltrate and a reduced extent of fibrosis were observed in the PVE group only. CONCLUSIONS: Use of 18F-FDG-PET/CT at the initial presentation of patients with suspected PVE increases the diagnostic capability of the modified Duke criteria. In patients who present with suspected NVE, the use of 18F-FDG-PET/CT is less accurate and could only be considered a complementary diagnostic tool for a specific population of patients with NVE.

Non-toxigenic Corynebacterium diphtheriae infective endocarditis with embolic events: a case report.

BACKGROUND: Corynebacterium diphtheriae (C. diphtheriae) infections, usually related to upper airways involvement, could be highly invasive. Especially in developing countries, non-toxigenic C. diphtheriae strains are now emerging as cause of invasive disease like endocarditis. The present case stands out for reinforcing the high virulence of this pathogen, demonstrated by the multiple systemic embolism and severe valve deterioration. It also emphasizes the importance of a coordinated interdisciplinary work to address all these challenges related to infectious endocarditis. CASE PRESENTATION: A 21-year-old male cocaine drug abuser presented to the emergency department with a 1-week history of fever, asthenia and dyspnea. His physical examination revealed a mitral systolic murmur, signs of acute arterial occlusion of the left lower limb, severe arterial hypotension and acute respiratory failure, with need of vasoactive drugs, orotracheal intubation/mechanical ventilation, empiric antimicrobial therapy and emergent endovascular treatment. The clinical suspicion of acute infective endocarditis was confirmed by transesophageal echocardiography, demonstrating a large vegetation on the mitral valve associated with severe valvular regurgitation. Abdominal ultrasound was normal with no hepatic, renal, or spleen abscess. Serial blood cultures and thrombus culture, obtained in the vascular procedure, identified non-toxigenic C. diphtheriae, with antibiotic therapy adjustment to monotherapy with ampicillin. Since the patient had a severe septic shock with sustained fever, despite antimicrobial therapy, urgent cardiac surgical intervention was planned. Anatomical findings were compatible with an aggressive endocarditis, requiring mitral valve replacement for a biological prosthesis. During the postoperative period, despite an initial clinical recovery and successfully weaning from mechanical ventilation, the patient presented with a recrudescent daily fever. Computed tomography of the abdomen revealed a hypoattenuating and extensive splenic lesion suggestive of abscess. After sonographically guided bridging percutaneous catheter drainage, surgical splenectomy was performed. Despite left limb revascularization, a forefoot amputation was required due to gangrene. The patient had a good clinical recovery, fulfilling 4-weeks of antimicrobial treatment. CONCLUSION: Despite the effectiveness of toxoid-based vaccines, recent global outbreaks of invasive C. diphtheriae infectious related to non-toxigenic strains have been described. These infectious could be highly invasive as demonstrated in this case. Interdisciplinary work with an institutional "endocarditis team" is essential to achieve favorable clinical outcomes in such defiant scenarios.

Rhizopus arrhizus and Fusarium solani Concomitant Infection in an Immunocompromised Host.

Neutropenic patients are at risk of the development of hyalohyphomycosis and mucormycosis. Correct identification is essential for the initiation of the specific treatment, but concomitant mold infections are rarely reported. We report one unprecedented case of concomitant mucormycosis and fusariosis in a neutropenic patient with acute myeloid leukemia. The patient developed rhino-orbital infection by Rhizopus arrhizus and disseminated infection by Fusarium solani. The first culture from a sinus biopsy grew Rhizopus, which was consistent with the histopathology report of mucormycosis. A second sinus biopsy collected later during the patient's clinical deterioration was reported as hyalohyphomycosis, and the culture yielded F. solani. Due to the discordant reports, the second biopsy was reviewed and two hyphae types suggestive of both hyalohyphomycetes and mucormycetes were found. The dual mold infection was confirmed by PCR assays from paraffinized tissue sections. Increased awareness of the existence of dual mold infections in at-risk patients is necessary. PCR methods in tissue sections may increase the diagnosis of dual mold infections. In case of sequential biopsies showing discrepant results, mixed infections have to be suspected.

Bartonella spp. and Coxiella burnetii Associated with Community-Acquired, Culture-Negative Endocarditis, Brazil.

We evaluated culture-negative, community-acquired endocarditis by using indirect immunofluorescent assays and molecular analyses for Bartonella spp. and Coxiella burnetii and found a prevalence of 19.6% and 7.8%, respectively. Our findings reinforce the need to study these organisms in patients with culture-negative, community-acquired endocarditis, especially B. henselae in cat owners.

Pneumococcal infective endocarditis in Brazil: a multicenter study on a severe condition.

BACKGROUND: Streptococcus pneumoniae bacteremia may result in Infective Endocarditis (IE). In the pre-antibiotic era, it caused 10 %‒15 % of IE, decreasing to < 3 % after penicillin availability. Although infrequent, it causes aggressive disease. METHODS: Retrospective analysis of endocarditis databases, prospectively implemented in 4 Brazilian institutions, 2005‒2023. RESULTS: From the prospective cohorts comprising 2321 adult patients with IE, we identified 11 with pneumococcal IE. Males represented 7/11 and mean age was 54 years (22‒77). All had native valve involvement; perivalvular abscess was present in 6/11. Only one patient had concurrent meningitis. Beta-lactams were the antibiotics used in 10/11. All had surgical indication, but only 6 had it, as the others were seriously ill. Overall, in hospital mortality was 6/11, but only 1/6 of those who underwent surgery died, compared to 5/5 of those who had an indication for surgery and did not have it. CONCLUSIONS: The high mortality rates and need for surgical intervention emphasize the need to promptly identify and manage pneumococcal endocarditis. Physicians ought to recommend vaccination to all patients at risk for severe pneumococcal disease.

The Predictive Value of Sepsis Scores for In-Hospital Mortality in Patients with Left-Sided Infective Endocarditis.

BACKGROUND: As infective endocarditis has particular characteristics compared to other infectious diseases, it is not clear if sepsis scores are reported with good accuracy in these patients. The aim of this study is to evaluate the accuracy of the qSOFA and SOFA scores to predict mortality in patients with infective endocarditis. METHODS: Between January 2010 and June 2019, 867 patients with suspected left-sided endocarditis were evaluated; 517 were included with left-sided infective endocarditis defined as "possible" or "definite" endocarditis, according to the Modified Duke Criteria. ROC curves were constructed to assess the accuracy of qSOFA and SOFA sepsis scores for the prediction of in-hospital mortality. RESULTS: The median age was 57 years, 65% were male, 435 (84%) had pre-existing heart valve disease, and the overall mortality was 28%. The most frequent etiologies were Streptococcus spp. (36%), Enterococcus spp. (10%), and Staphylococcus aureus (9%). The sepsis scores from the ROC curves used to predict in-hospital mortality were qSOFA 0.601 (CI95% 0.522-0.681) and SOFA score 0.679 (CI95% 0.602-0.756). A sub-group analysis in patients with and without pre-existing valve disease for SOFA ≥ 2 showed ROC curves of 0.627 (CI95% 0.563-0.690) and 0.775 (CI95% 0.594-0.956), respectively. CONCLUSIONS: qSOFA and SOFA scores were associated with increased in-hospital mortality in patients with infective endocarditis. However, as accuracy was relatively lower compared to other sites of bacterial infections, we believe that this score may have lower accuracy when predicting the prognosis of patients with IE, because, in this disease, the patient's death may be more frequently linked to valvular and cardiac dysfunction, as well as embolic events, and less frequently directly associated with sepsis.

Changing trends in clinical characteristics and in-hospital mortality of patients with infective endocarditis over four decades.

BACKGROUND: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. METHODS: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978-1988, 1989-1999, 2000-2010 and 2011-2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. FINDINGS: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p < 0.001), with significant declines in the occurrence of rheumatic valvular heart disease (15% to 6%; p < 0.001) and streptococcal infections (46% to 33%; p < 0.001). Healthcare-associated infections have increased (9% to 21%; p < 0.001), as have prosthetic valve endocarditis (26% to 53%; p < 0.001), coagulase-negative staphylococcal infections (4% to 11%; p < 0.001), and related-complications (heart failure, embolic events, and perivalvular abscess; p < 0.001). These changes were associated with a decline in adjusted in-hospital mortality from 34% to 25% (p = 0.019). INTERPRETATION: In the 44 years studied, there was an increase in the mean age of patients, healthcare-related, prosthetic valve, coagulase-negative staphylococci/MRSA infections, and related complications. Notably, these epidemiological changes were associated with a decline in the adjusted in-hospital mortality.

Comparing plasma and skin imprint metabolic profiles in COVID-19 diagnosis and severity assessment.

As SARS-CoV-2 continues to produce new variants, the demand for diagnostics and a better understanding of COVID-19 remain key topics in healthcare. Skin manifestations have been widely reported in cases of COVID-19, but the mechanisms and markers of these symptoms are poorly described. In this cross-sectional study, 101 patients (64 COVID-19 positive patients and 37 controls) were enrolled between April and June 2020, during the first wave of COVID-19, in São Paulo, Brazil. Enrolled patients had skin imprints sampled non-invasively using silica plates; plasma samples were also collected. Samples were used for untargeted lipidomics/metabolomics through high-resolution mass spectrometry. We identified 558 molecular ions, with lipids comprising most of them. We found 245 plasma ions that were significant for COVID-19 diagnosis, compared to 61 from the skin imprints. Plasma samples outperformed skin imprints in distinguishing patients with COVID-19 from controls, with F1-scores of 91.9% and 84.3%, respectively. Skin imprints were excellent for assessing disease severity, exhibiting an F1-score of 93.5% when discriminating between patient hospitalization and home care statuses. Specifically, oleamide and linoleamide were the most discriminative biomarkers for identifying hospitalized patients through skin imprinting, and palmitic amides and N-acylethanolamine 18:0 were also identified as significant biomarkers. These observations underscore the importance of primary fatty acid amides and N-acylethanolamines in immunomodulatory processes and metabolic disorders. These findings confirm the potential utility of skin imprinting as a valuable non-invasive sampling method for COVID-19 screening; a method that may also be applied in the evaluation of other medical conditions. KEY MESSAGES: Skin imprints complement plasma in disease metabolomics. The annotated markers have a role in immunomodulation and metabolic diseases. Skin imprints outperformed plasma samples at assessing disease severity. Skin imprints have potential as non-invasive sampling strategy for COVID-19.

Risk Factors for Surgical Site Infection in Patients Undergoing Pediatric Cardiac Surgery. / Fatores de Risco para Infecção da Ferida Operatória em Pacientes Submetidos à Cirurgia Cardíaca Pediátrica.

BACKGROUND: Central Illustration : Risk Factors for Surgical Site Infection in Patients Undergoing Pediatric Cardiac Surgery Risk factors for surgical site infection in patients undergoing pediatric cardiac surgery. BACKGROUND: Surgical site infection is an important complication after pediatric cardiac surgery, associated with increased morbidity and mortality. OBJECTIVES: We sought to identify risk factors for surgical site infection after pediatric cardiac surgeries. METHODS: A case-control study included patients aged between 1 year and 19 years and 11 months of age, submitted to cardiac surgery performed at a tertiary cardiac center from January 1 st , 2011, through December 31, 2018. Charts were reviewed for pre-, intra, and postoperative variables. We identified two randomly selected control patients with the same pathophysiological diagnosis and underwent surgery within thirty days of each index case. Univariate and multivariate logistic regression analyses were performed to identify risk factors. Statistical significance was defined as p<0.05. RESULTS: Sixty-six cases and 123 controls were included. Surgical site infection incidence ranged from 2% to 3.8%. The following risk factors were identified: Infant age (OR 3.19, 95% CI 1.26 to 8.66, p=0.014), presence of genetic syndrome (OR 6.20, CI 95% 1.70 to 21.65, p=0.004), categories 3 and 4 of RACHS-1 (OR 8.40, CI 95% 3.30 to 21.34, p<0.001), 48 h C-reactive protein level range was detected as a protective factor for this infection (OR 0.85, 95% CI 0.73 to 0.98, p=0.023). CONCLUSIONS: The risk factors defined in this study could not be modified. Therefore, additional surveillance and new preventive strategies need to be implemented to reduce the incidence of surgical site infection. The increased CRP in the postoperative period was a protective factor that needs further understanding.

Infective Endocarditis due to Non-HACEK Gram-Negative Bacilli: Clinical Characteristics and Risk Factors from a Prospective Multicenter Brazilian Cohort.

Background: Non-HACEK Gram-negative bacilli (NGNB) infective endocarditis (IE) has a growing frequency. We aimed to describe cases of NGNB IE and find associated risk factors. Methods: We conducted a prospective observational study of consecutive patients with definitive IE according to the modified Duke criteria in four institutions in Brazil. Results: Of 1154 adult patients enrolled, 38 (3.29%) had IE due to NGNB. Median age was 57 years, males predominated, accounting for 25/38 (65.8%). Most common etiologies were Pseudomonas aeruginosa and Klebsiella spp. (8 episodes, 21% each). Worsening heart failure occurred in 18/38 (47.4%). Higher prevalence of embolic events was found (55,3%), mostly to the central nervous system 7/38 (18.4%). Vegetations were most commonly on aortic valves 17/38 (44.7%). Recent healthcare exposure was found in 52.6% and a central venous catheter (CVC) in 13/38 (34.2%). Overall mortality was 19/38 (50%). Indwelling CVC (OR 5.93; 95% CI, 1.29 to 27.3; p = 0.017), hemodialysis (OR 16.2; 95% CI, 1.78 to 147; p = 0.008) and chronic kidney disease (OR 4.8; 95% IC, 1.2 to 19.1, p = 0.049) were identified as risk factors for mortality. Conclusions: The rate of IE due to NGNB was similar to that in previous studies. Enterobacterales and P. aeruginosa were the most common etiologies. NGNB IE was associated with central venous catheters, prosthetic valves, intracardiac devices and hemodialysis and had a high mortality rate.

A Brazilian Inter-Hospital Candidemia Outbreak Caused by Fluconazole-Resistant Candida parapsilosis in the COVID-19 Era.

Horizontal transmission of fluconazole-resistant Candida parapsilosis (FRCP) through healthcare workers' hands has contributed to the occurrence of candidemia outbreaks worldwide. Since the first COVID-19 case in Brazil was detected in early 2020, hospitals have reinforced hand hygiene and disinfection practices to minimize SARS-CoV-2 contamination. However, a Brazilian cardiology center, which shares ICU patients with a cancer center under a FRCP outbreak since 2019, reported an increased FRCP candidemia incidence in May 2020. Therefore, the purpose of this study was to investigate an inter-hospital candidemia outbreak caused by FRCP isolates during the first year of the COVID-19 pandemic in Brazil. C. parapsilosis bloodstream isolates obtained from the cancer (n = 35) and cardiology (n = 30) centers in 2020 were submitted to microsatellite genotyping and fluconazole susceptibility testing. The ERG11 gene of all isolates from the cardiology center was sequenced and compared to the corresponding sequences of the FRCP genotype responsible for the cancer center outbreak in 2019. Unprecedentedly, most of the FRCP isolates from the cardiology center presented the same genetic profile and Erg11-Y132F mutation detected in the strain that has been causing the persistent outbreak in the cancer center, highlighting the uninterrupted horizontal transmission of clonal isolates in our hospitals during the COVID-19 pandemic.

Characteristics and Outcomes of Heart Transplant Recipients With Coronavirus-19 Disease in a High-volume Transplant Center.

BACKGROUND: Heart transplant (HT) recipients may be at higher risk of acquiring SARS-CoV-2 infection and developing critical illness. The aim of this study is to describe characteristics and outcomes of HT recipients infected by SARS-COV-2, from a high-volume transplant center. METHODS: We have described data of all adult HT recipients with confirmed coronavirus disease 2019 by RT-PCR in nasopharyngeal samples from April 5, 2020, to January 5, 2021. Outcomes and follow-up were recorded until February 5, 2021. RESULTS: Forty patients were included. Twenty-four patients (60%) were men; the median age was 53 (40-60) y old; median HT time was 34 mo; and median follow-up time 162 d. The majority needed hospitalization (83%). Immunosuppressive therapy was reduced/withdrawn in the majority of patients, except from steroids, which were maintained. Seventeen patients (42.5%) were classified as having severe disease according to the ordinal scale developed by the World Health Organization Committee. They tended to have lower absolute lymphocyte count (P < 0.001) during follow-up when compared with patients with mild disease. Thirty-day mortality was 12.5%. However, a longer follow-up revealed increased later mortality (27.5%), with median time to death around 35 d. Bacterial nosocomial infections were a leading cause of death. Cardiac allograft rejection (10%) and ventricular dysfunction (12.5%) were also not negligible. CONCLUSIONS: Major findings of this study corroborate other cohorts' results, but it also reports significant rate of later events, suggesting that a strict midterm surveillance is advisable to HT recipients with coronavirus disease 2019.

The "false-positive" conundrum: IgA reference level overestimates the seroprevalence of antibodies to SARS-CoV-2.

BACKGROUND: On 12 June 2020, Brazil reached the second position worldwide in the number of COVID-19 cases. Authorities increased the number of tests performed, including the identification of antibodies to SARS-CoV-2 (IgG, IgA, and IgM). There was an overflooding of the market with several tests, and the presence of possible false-positive results became a challenge. The purpose of this study was to describe the seroprevalence and immunoglobulin blood levels in a group of asymptomatic individuals using the reference levels provided by the manufacturer. METHODS: Levels of IgG and IgA antibodies to SARS-CoV-2 were determined in blood serum by the same ELISA (enzyme-linked immunoassay) test. Patients must be free of symptoms. RESULTS: From 20 to 22 May 2020, 938 individuals were tested. There were 441 (47%) men, age 53 years (interquartile range (IQR) = 39-63.2). The sample included 335 (35.7%) subjects aged ≥60 years old. Subjects with a positive test were 54 (5.8%) for IgG and 96 (10.2%) for IgA and 42 (4.5%) for both IgG and IgA. The prevalence of IgG and IgA positive test was not different in men and women and not different in individuals under 60 and over 60 years of age. Conversely, analysing only individuals with positive tests, the levels of IgG in positive subjects were significantly higher than those with an IgA positive test, 3.00 (IQR = 1.68-5.65), and 1.95 (IQR = 1.40-3.38), respectively; P = 0.017. Additionally, individuals with isolated IgA positive tests had significantly lower levels of IgA than those with both IgA and IgG positive tests: 1.95 (IQR = 1.60-2.40) and 3.15 (IQR = 2.20-3.90), respectively, P = 0.005. These latter data suggest that IgA shows a deviation of the distribution to the left in comparison to IgG distribution data. Indeed, many subjects reported as IgA positive had immunoglobulin levels slightly elevated. CONCLUSIONS: In conclusion, we strongly suggest caution in the interpretation of IgA test results. This recommendation is more important for those with positive IgA just above the reference level.

Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance.

BACKGROUND: Hydroxychloroquine has shown potential to block viral replication of SARS-CoV-2 in some in vitro studies. This randomised, double-blinded, placebo controlled clinical trial evaluated the efficacy of hydroxychloroquine plus azithromycin (HCQ/AZT) in reducing viral loads in patients with early and mild SARS-CoV-2 infection. METHODS: A single-centre randomised placebo-controlled clinical trial was conducted with outpatients with early and mild SARS-CoV-2 infection. Inclusion criteria were: patients aged 18-65 years with symptoms suggestive of COVID-19 for < 5 days, no significant comorbidities, and positive nasopharyngeal/oropharyngeal swab screening tests (POCT-PCR). Randomised patients received either hydroxychloroquine for 7 days plus azithromycin for 5 days or placebo. The primary endpoint was viral clearance within a 9-day period. Secondary endpoints included viral load reduction, clinical evolution, hospitalization rates, chest computed tomography evolution, and adverse effects. RESULTS: From 107 potential trial participants, 84 were enrolled following predetermined criteria. Statistical analyses were performed on an intention-to-treat (N = 84) and per-protocol (PP) basis (N = 70). On the PP analysis, the treatment (N = 36) and placebo (N = 34) groups displayed similar demographic characteristics. At 95% CI, no statistically significant between-group differences were found in viral clearance rates within 9 days following enrolment (P = 0.26). CONCLUSIONS: This randomised, double-blinded, placebo-controlled clinical trial evaluating outpatients with early and mild COVID-19 showed that viral clearance rates within a 9-day period from enrolment did not change with HCQ/AZT treatment compared with placebo, although no major cardiovascular events were observed in participants without comorbidities. Secondary outcomes were also not significantly improved with HCQ/AZT treatment compared with placebo. These findings do not support use of HCQ/AZT in this setting.

The Child Emotion Facial Expression Set: A Database for Emotion Recognition in Children.

Background: This study developed a photo and video database of 4-to-6-year-olds expressing the seven induced and posed universal emotions and a neutral expression. Children participated in photo and video sessions designed to elicit the emotions, and the resulting images were further assessed by independent judges in two rounds. Methods: In the first round, two independent judges (1 and 2), experts in the Facial Action Coding System, firstly analysed 3,668 emotions facial expressions stimuli from 132 children. Both judges reached 100% agreement regarding 1,985 stimuli (124 children), which were then selected for a second round of analysis between judges 3 and 4. Results: The result was 1,985 stimuli (51% of the photographs) were produced from 124 participants (55% girls). A Kappa index of 0.70 and an accuracy of 73% between experts were observed. Lower accuracy was found for emotional expression by 4-year-olds than 6-year-olds. Happiness, disgust and contempt had the highest agreement. After a sub-analysis evaluation of all four judges, 100% agreement was reached for 1,381 stimuli which compound the ChildEFES database with 124 participants (59% girls) and 51% induced photographs. The number of stimuli of each emotion were: 87 for neutrality, 363 for happiness, 170 for disgust, 104 for surprise, 152 for fear, 144 for sadness, 157 for anger 157, and 183 for contempt. Conclusions: The findings show that this photo and video database can facilitate research on the mechanisms involved in early childhood recognition of facial emotions in children, contributing to the understanding of facial emotion recognition deficits which characterise several neurodevelopmental and psychiatric disorders.

Demographic, cardiological, microbiologic, and dental profiles of Brazilian patients who developed oral bacteria-related endocarditis.

OBJECTIVE: Infective endocarditis (IE) may cause devastating complications with high morbidity and mortality rates. The aim of the present study was to study the demographic, cardiological, microbiologic, and dental profiles of patients with oral bacteria-related IE. STUDY DESIGN: We present a retrospective study of patients with oral bacteria-related IE treated at Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil, between January 2009 and December 2019. RESULTS: Of the 100 patients included, 70% were male with a mean age of 45.4 years at diagnosis. The most affected sites were aortic and mitral valves, 60% in prosthetic heart valves, 34% in native valves, and 3% in pacemakers. The most common cause of valvular disease was rheumatic cardiopathy (51.9%), and the most frequent complications were valvular and perivalvular damage (26%). Streptococcus viridans was the most common species (96%), dental caries were present in 57% of the patients, 78% had tooth loss, 45% had apical periodontitis, and 77% were at high/moderate risk for periodontal disease. CONCLUSION: Oral bacteria-related IE among Brazilians was predominant in the prosthetic heart valves of young male adults previously affected by rheumatic cardiopathy. Streptococcus viridans was the main cause of IE, which was linked to patients with a poor oral health status.

Prognostic accuracy of MALDI-TOF mass spectrometric analysis of plasma in COVID-19.

SARS-CoV-2 infection poses a global health crisis. In parallel with the ongoing world effort to identify therapeutic solutions, there is a critical need for improvement in the prognosis of COVID-19. Here, we report plasma proteome fingerprinting that predict high (hospitalized) and low-risk (outpatients) cases of COVID-19 identified by a platform that combines machine learning with matrix-assisted laser desorption ionization mass spectrometry analysis. Sample preparation, MS, and data analysis parameters were optimized to achieve an overall accuracy of 92%, sensitivity of 93%, and specificity of 92% in dataset without feature selection. We identified two distinct regions in the MALDI-TOF profile belonging to the same proteoforms. A combination of SDS-PAGE and quantitative bottom-up proteomic analysis allowed the identification of intact and truncated forms of serum amyloid A-1 and A-2 proteins, both already described as biomarkers for viral infections in the acute phase. Unbiased discrimination of high- and low-risk COVID-19 patients using a technology that is currently in clinical use may have a prompt application in the noninvasive prognosis of COVID-19. Further validation will consolidate its clinical utility.

Platelet Reactivity and Coagulation Markers in Patients with COVID-19.

INTRODUTION: COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. METHODS: Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups. RESULTS: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group. CONCLUSION: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04447131.