SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil.

The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma in Amazonas during early 2021 fueled a second large COVID-19 epidemic wave and raised concern about the potential role of reinfections. Very few cases of reinfection associated with the VOC Gamma have been reported to date, and their potential impact on clinical, immunological, and virological parameters remains largely unexplored. Here we describe 25 cases of SARS-CoV-2 reinfection in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected with distinct viral lineages between March and December 2020 (B.1.1, B.1.1.28, B.1.1.33, B.1.195, and P.2) and reinfected with the VOC Gamma between 3 to 12 months after primo-infection. We found a similar mean cycle threshold (Ct) value and limited intra-host viral diversity in both primo-infection and reinfection samples. Sera of 14 patients tested 10-75 days after reinfection displayed detectable neutralizing antibodies (NAb) titers against SARS-CoV-2 variants that circulated before (B.1.*), during (Gamma), and after (Delta and Omicron) the second epidemic wave in Brazil. All individuals had milder or no symptoms after reinfection, and none required hospitalization. These findings demonstrate that individuals reinfected with the VOC Gamma may display relatively high RNA viral loads at the upper respiratory tract after reinfection, thus contributing to onward viral transmissions. Despite this, our study points to a low overall risk of severe Gamma reinfections, supporting that the abrupt increase in hospital admissions and deaths observed in Amazonas and other Brazilian states during the Gamma wave was mostly driven by primary infections. Our findings also indicate that most individuals analyzed developed a high anti-SARS-CoV-2 NAb response after reinfection that may provide some protection against reinfection or disease by different SARS-CoV-2 variants.

Should COVID-19 be branded to viral thrombotic fever?

Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year's time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a "thrombotic storm," much more than a "cytokine storm." The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.

Three SARS-CoV-2 reinfection cases by the new Variant of Concern (VOC) P.1/501Y.V3

Neste relatório (pre-print), são apresentados três casos de reinfecção causados pela Variante de Preocupação (VOC) P.1, também conhecida como "cepa de Manaus". As três pacientes eram mulheres adultas, e tiveram a primeira infecção durante a primeira onda da pandemia na primeira metade de 2020. Nos três casos, a linhagem detectada no primeiro diagnóstico molecular era diferente da encontrada posteriormente, evidência da reinfecção. Dois dos casos de reinfecção tiveram apresentação de sintomas leves, enquanto o terceiro foi assintomático, apesar de a quantidade de material genético viral detectado sugerir cargas virais elevadas. As evidências aqui apresentadas sugerem que a imunidade após infecção primária por linhagens anteriores à circulação daquelas contendo a mutação E484K não impede uma nova infecção pela variante P.1, e nem mesmo que pessoas reinfectadas por esta variante espalhem o vírus, embora seja possível que tenha protegido estas três pacientes do desenvolvimento de sintomas graves.

Decrease in Attentional Performance After Repeated Bouts of High Intensity Exercise in Association-Football Referees and Assistant Referees.

Referees and assistant referees are submitted to high physical stress during matches. Pressure to make decisions in front of large crowds is another potential stressor. These two stressors can impair attention executive control, depending on physical fitness and individual vulnerability or resilience to situational pressure. Error percentage for referees and assistants may reach around 14% during a soccer match. Although previous studies have suggested that soccer referees and assistants should take cognitive assessments, they are only required by Fédération Internationale de Football Association (FIFA) to demonstrate knowledge of the rules and pass annually in a fitness test (FIFA-Test). This study aimed to assess attention performance in referees and assistants before and after the mandatory FIFA-Test. It is hypothesized that the high physical demands associated with the pressure to pass the FIFA-Test would interfere with attention performance. The sample included 33 referees and 20 assistants. The Continuous Visual Attention Test (CVAT) consisted of a 15-min Go/No-go task. Performance in the CVAT is based on four variables: omission and commission errors, reaction time, and variability of reaction time (VRT). Failure in the CVAT was defined by a performance below the 5th percentile of the age- and sex-matched normative data in at least one variable of the CVAT. Before the FIFA-Test all participants performed the CVAT. The second CVAT began 3-7 min directly following completion of the FIFA-test. Considering only the officials who passed both the FIFA-Test and the first CVAT (19 referees and 15 assistants), 44% (9 referees and 6 assistants) exhibited a performance decline in the second CVAT. A significant increase in VRT was found after the high intensity exercise. As increase in VRT is thought to reflect executive dysfunctions and lapses of attention, we concluded that physical fitness alone may not be enough to help officials cope with the physical and contextual stresses associated with the FIFA-Test. These data suggest that over 35% of soccer referees and their assistants who were considered physically able to referee matches may not be mentally prepared for the attentional demands of refereeing soccer matches.

Impact of an inpatient multidisciplinary glucose control management program.

OBJECTIVE: Glycemic control has been increasingly recognized as a critical element in inpatient care, but optimal management of blood glucose in the hospital setting remains challenging. The aims of this study were to describe and evaluate the impact of the implementation of an inpatient multidisciplinary glucose control management program on glucose control in hospitalized patients. MATERIALS AND METHODS: Retrospective analysis of medical records and glucose monitoring data obtained by point- of-care testing (POCT) in hospitalized patients before (May 2014) and after (June 2015 and May 2017) the implementation of the program. RESULTS: We analyzed 6888, 7290, and 7669 POCTs from 389, 545, and 475 patients in May 2014, June 2015, and May 2017, respectively. Hyperglycemia (≥ 180 mg/ dL) occurred in 23.5%, 19.6%, and 19.3% POCTs in May 2014, June 2015, and May/2017, respectively (p < 0.001), while severe hyperglycemia (≥ 300 mg/dL) was observed in 2.5%, 2.2%, and 1.8% of them, respectively (p = 0.003). Hyperglycemia (≥ 180 mg/dL) reduced significantly from May 2014 to June 2015 (16.3%, p < 0.001) and from May 2014 to May 2017 (178%, p < 0.001). No significant changes occurred in hypoglycemic parameters. CONCLUSIONS: The implementation of an inpatient multidisciplinary glucose control management program led to significant reductions in hyperglycemic events. The key elements for this achievement were the development of institutional inpatient glycemic control protocols, establishment of a multidisciplinary team, and continuing educational programs for hospital personnel. Altogether, these actions resulted in improvements in care processes, patient safety, and clinical outcomes of hospitalized patients.

Impact of an inpatient multidisciplinary glucose control management program

ABSTRACT Objective: Glycemic control has been increasingly recognized as a critical element in inpatient care, but optimal management of blood glucose in the hospital setting remains challenging. The aims of this study were to describe and evaluate the impact of the implementation of an inpatient multidisciplinary glucose control management program on glucose control in hospitalized patients. Materials and methods: Retrospective analysis of medical records and glucose monitoring data obtained by point- of-care testing (POCT) in hospitalized patients before (May 2014) and after (June 2015 and May 2017) the implementation of the program. Results: We analyzed 6888, 7290, and 7669 POCTs from 389, 545, and 475 patients in May 2014, June 2015, and May 2017, respectively. Hyperglycemia (≥ 180 mg/ dL) occurred in 23.5%, 19.6%, and 19.3% POCTs in May 2014, June 2015, and May/2017, respectively (p < 0.001), while severe hyperglycemia (≥ 300 mg/dL) was observed in 2.5%, 2.2%, and 1.8% of them, respectively (p = 0.003). Hyperglycemia (≥ 180 mg/dL) reduced significantly from May 2014 to June 2015 (16.3%, p < 0.001) and from May 2014 to May 2017 (178%, p < 0.001). No significant changes occurred in hypoglycemic parameters. Conclusions: The implementation of an inpatient multidisciplinary glucose control management program led to significant reductions in hyperglycemic events. The key elements for this achievement were the development of institutional inpatient glycemic control protocols, establishment of a multidisciplinary team, and continuing educational programs for hospital personnel. Altogether, these actions resulted in improvements in care processes, patient safety, and clinical outcomes of hospitalized patients.

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial.

INTRODUCTION: There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. METHODS: We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression. RESULTS: In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. CONCLUSIONS: In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone.

Fulminant liver failure in a street runner: Effects of heat stroke.

We present a clinical case of liver failure induced by heat stroke.

Occult Breast Carcinoma Presenting as Scalp Metastasis.

Breast cancer is the most common tumor among women, and approximately 6% of the patients have de novo metastatic breast cancer. Occult breast cancer accounts for only 0.1-0.8% of the cases and most commonly presents with axillary lymphadenopathy. Scalp metastases are rare and have been described as a sign of progression or widespread metastatic disease. Here, we describe a rare case of de novo metastatic breast cancer to the scalp as the single site of spread and without an identifiable primary breast tumor.

Platelets: an outlook from biology through evidence-based achievements in critical care.

Since the original observations by Bizzozero and Osler, we have seen tremendous advances in the understanding of platelets far beyond haemostasis and the restoration of injured endothelium. In this mini-review on platelets, we will briefly outline their historical description and the importance of their evolution, focusing on a 450 million years old living fossil of Limulus polyphemus, a marine chelicerate arthropod, which helped researchers explain the basis for the immunity role of platelets and make correlations with platelet ultrastructure and function. In addition, the impact of the Limulus Amoebocyte Lysate (LAL) test for modern medicine is highlighted. The role of platelets in cardiovascular diseases, their relevance in arterial and venous thrombosis, and the utilization of antithrombotic drugs as therapeutic agents are also reported. Furthermore, platelet receptors are crucial in aggravating or mitigating other diseases, such as cancer and infections, which can recruit cells and have numerous interactions in a process recently coined "NETosis formation", which is also briefly depicted.

Interstitial Pneumonitis Secondary to Trastuzumab: A Case Report and Literature Review.

Interstitial lung disease is a rare complication of trastuzumab-based breast cancer treatment with few case reports published. Herein, we report the case of a 67-year-old female with early-stage HER2-postitive breast cancer who developed interstitial pneumonitis during cycle 5 of treatment with trastuzumab combined with carboplatin and docetaxel. After supportive care and treatment with prednisone, the patient showed rapid improvement of respiratory symptoms. Retreatment with trastuzumab as a single agent led to worsening of symptoms and required a second course of treatment with prednisone combined with cyclophosphamide, which was followed by improvement of symptoms. In conclusion, interstitial pneumonitis is a rare but life-threatening adverse event from trastuzumab breast cancer treatment.

Over 50 Years of Fibrinogen Concentrate.

March 2013 represented the 50th anniversary of the first license granted for a fibrinogen concentrate. In this review, we look at the history of bleeding management that led to the development of fibrinogen concentrate, discuss its current use, and consider future developments for this product.

Caixa de atividades diárias para ratos / Daily activities box for rats

Este trabalho apresenta um protótipo de caixa de condicionamento operante para ratos - batizada de Caixa de Atividades Diárias Para Ratos - que permite o registro, 24h por dia, de múltiplos operantes. O sujeito experimental pode ser remotamente monitorado (visto e ouvido em tempo real) por meio de uma webcam localizada na frente da caixa. Além disso, todas as funções do equipamento podem ser controladas remotamente via internet. Trata-se da primeira caixa experimental a reunir todas estas funções, ao menos no Brasil. Algumas sugestões de áreas de pesquisa em que o equipamento poderia ser utilizado são apresentadas.(AU)

This work presents a prototype of an operant conditioning box for mice - named Daily Activities Box for Rats -, in which multiple operants can be recorded 24 h per day. The experimental subject can be monitored remotely (seen and heard in real time) by means of a webcam located in front of the box. Furthermore, all the equipment functions can be controlled remotely via internet. This is the first experimental box to gather all these functions, at least in Brazil. Some suggestions of areas of research in which the equipment may be used are presented.(AU)

Caixa de atividades diárias para ratos / Daily activities box for rats

Este trabalho apresenta um protótipo de caixa de condicionamento operante para ratos - batizada de Caixa de Atividades Diárias Para Ratos - que permite o registro, 24h por dia, de múltiplos operantes. O sujeito experimental pode ser remotamente monitorado (visto e ouvido em tempo real) por meio de uma webcam localizada na frente da caixa. Além disso, todas as funções do equipamento podem ser controladas remotamente via internet. Trata-se da primeira caixa experimental a reunir todas estas funções, ao menos no Brasil. Algumas sugestões de áreas de pesquisa em que o equipamento poderia ser utilizado são apresentadas...

This work presents a prototype of an operant conditioning box for mice - named Daily Activities Box for Rats -, in which multiple operants can be recorded 24 h per day. The experimental subject can be monitored remotely (seen and heard in real time) by means of a webcam located in front of the box. Furthermore, all the equipment functions can be controlled remotely via internet. This is the first experimental box to gather all these functions, at least in Brazil. Some suggestions of areas of research in which the equipment may be used are presented...

Viability of human adenovirus from hospital fomites.

The monitoring of environmental microbial contamination in healthcare facilities may be a valuable tool to determine pathogens transmission in those settings; however, such procedure is limited to bacterial indicators. Viruses are found commonly in those environments and are rarely used for these procedures. The aim of this study was to assess distribution and viability of a human DNA virus on fomites in an Adult Intensive Care Unit of a private hospital in Rio de Janeiro, Brazil. Human adenoviruses (HAdV) were investigated in 141 fomites by scraping the surface area and screening by quantitative PCR (qPCR) using TaqMan® System (Carlsbad, CA). Ten positive samples were selected for virus isolation in A549 and/or HEp2c cell lines. A total of 63 samples (44.7%) were positive and presented viral load ranging from 2.48 × 10(1) to 2.1 × 10(3) genomic copies per millilitre (gc/ml). The viability was demonstrated by integrated cell culture/nested-PCR in 5 out of 10 samples. Nucleotide sequencing confirmed all samples as HAdV and characterized one of them as specie B, serotype 3 (HAdV-3). The results indicate the risk of nosocomial transmission via contaminated fomites and point out the use of HAdV as biomarkers of environmental contamination.

Brazilian experience in EU-CORE: daptomycin registry and treatment of serious Gram-positive infections

OBJECTIVES: To collect data about non-controlled prescribing use of daptomycin and its impact among Brazilian patients with serious Gram positive bacterial infection, as well as the efficacy and safety outcomes. MATERIALS AND METHODS: This is a multi-center, retrospective, non-interventional registry (August 01, 2009 to June 30, 2011) to collect data on 120 patients (44 patients in the first year and 76 patients in the second year) who had received at least one dose of commercial daptomycin in Brazil for the treatment of serious Gram-positive bacterial infection. RESULTS: Right-sided endocarditis (15.8%), complicated skin and soft tissue infections (cSSTI)wound (15.0%) and bacteremia-catheter-related (14.2%) were the most frequent primary infections; lung (21.7%) was the most common site for infection. Daptomycin was used empirically in 76 (63.3%) patients, and methicillin-resistant Staphylococcus aureus (MRSA) was the most common suspected pathogen (86.1%). 82.5% of the cultures were obtained prior to or shortly after initiation of daptomycin therapy. Staphylococcus spp. - coagulase negative, MRSA, and methicillin-susceptible S. aureus were the most frequently identified pathogens (23.8%, 23.8% and 12.5%, respectively). The most common daptomycin dose administered for bacteremia and cSSTI was 6 mg/kg (30.6%) and 4 mg/kg (51.7%), respectively. The median duration of inpatient daptomycin therapy was 14 days. Most patients (57.1%) did not receive daptomycin while in intensive care unit. Carbapenem (22.5%) was the most commonly used antibiotic concomitantly. The patients showed clinical improvement after two days (median) following the start of daptomycin therapy. The clinical success rate was 80.8% and the overall rate of treatment failure was 10.8%. The main reasons for daptomycin discontinuation were successful end of therapy (75.8%), switched therapy (11.7%), and treatment failure (4.2%). Daptomycin demonstrated a favorable safety and tolerability profile regardless of treatment duration. CONCLUSIONS: Daptomycin had a relevant role in the treatment of Gram-positive infections in the clinical practice setting in Brazil.

Brazilian experience in EU-CORE: daptomycin registry and treatment of serious Gram-positive infections.

OBJECTIVES: To collect data about non-controlled prescribing use of daptomycin and its impact among Brazilian patients with serious Gram positive bacterial infection, as well as the efficacy and safety outcomes. MATERIALS AND METHODS: This is a multi-center, retrospective, non-interventional registry (August 01, 2009 to June 30, 2011) to collect data on 120 patients (44 patients in the first year and 76 patients in the second year) who had received at least one dose of commercial daptomycin in Brazil for the treatment of serious Gram-positive bacterial infection. RESULTS: Right-sided endocarditis (15.8%), complicated skin and soft tissue infections (cSSTI)-wound (15.0%) and bacteremia-catheter-related (14.2%) were the most frequent primary infections; lung (21.7%) was the most common site for infection. Daptomycin was used empirically in 76 (63.3%) patients, and methicillin-resistant Staphylococcus aureus (MRSA) was the most common suspected pathogen (86.1%). 82.5% of the cultures were obtained prior to or shortly after initiation of daptomycin therapy. Staphylococcus spp. - coagulase negative, MRSA, and methicillin-susceptible S. aureus were the most frequently identified pathogens (23.8%, 23.8% and 12.5%, respectively). The most common daptomycin dose administered for bacteremia and cSSTI was 6mg/kg (30.6%) and 4mg/kg (51.7%), respectively. The median duration of inpatient daptomycin therapy was 14 days. Most patients (57.1%) did not receive daptomycin while in intensive care unit. Carbapenem (22.5%) was the most commonly used antibiotic concomitantly. The patients showed clinical improvement after two days (median) following the start of daptomycin therapy. The clinical success rate was 80.8% and the overall rate of treatment failure was 10.8%. The main reasons for daptomycin discontinuation were successful end of therapy (75.8%), switched therapy (11.7%), and treatment failure (4.2%). Daptomycin demonstrated a favorable safety and tolerability profile regardless of treatment duration. CONCLUSIONS: Daptomycin had a relevant role in the treatment of Gram-positive infections in the clinical practice setting in Brazil.

Group A rotavirus detection on environmental surfaces in a hospital intensive care unit.

BACKGROUND: Environmental surfaces can play a role in the spread of pathogens, such as enteric viruses, within a hospital. This study assessed the level of contamination of group A rotavirus (RV-A) on environmental surfaces samples from an adult intensive care unit in a hospital in Rio de Janeiro, Brazil. METHODS: A total of 504 environmental surface samples were obtained from multiple sites in the intensive care unit, including flushing buttons, telephones, and alcohol gel supports. Nested and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) were used to detect and quantify RV-A levels through partial amplification of VP6 and NSP3 genes, respectively, and the viability of the viruses detected was assessed by MA-104 cell integrated cell culture/RT-PCR. RESULTS: RV-A was detected by nested RT-PCR in 14% of the samples (73 of 504), with viral loads ranging from 3.4 genomic copies/mL to 2.9 × 10(3) genomic copies/mL. The nucleotide sequence of the amplicons obtained from nested RT-PCR confirmed that the positive samples were RV-A. Moreover, 3 of 10 strains investigated demonstrated viability by integrated cell culture/RT-PCR. CONCLUSION: The detection of RV-A on environmental surface samples indicates a need for improvements to hospital cleaning procedures to reduce viral contamination, and suggests, as reported previously, that RV-A can be used as a biomarker to assess contamination in hospitals.

Circadian rhythm of hospital deaths: comparison between intensive care unit and non-intensive care unit.

OBJECTIVE: The demonstration that cardiovascular mortality follows a circadian rhythm led us to verify whether patients dying at the intensive unit care (ICU) and at the non-intensive unit care (non-ICU) follow that rhythm. METHODS: All hospital's deaths occurring between January 1, 2006 and July 31, 2010 were analyzed. The circadian pattern of the time of death was analyzed in twelve 2 hour intervals. The Chi-square test was used to compare proportions, and Student's t test or ANOVA single factor to compare continuous variables. A p-value < 0.05 was considered statistically significant. RESULTS: During the study period 700 deaths occurred in the hospital, 211 (30.1%) at the ICU and 88 (12.6%) at the non-ICU. There were more deaths in the first hours of the day, between 6 am and 12 am, at the non-ICU in comparison to the ICU (38% vs. 21%; p = 0.004). In the ICU, we observed that 21% of the deaths occurred between 6 am and 12 pm, 30% between 12 pm and 6 pm, 26% between 6 pm and 12 am and 24% between 12 am and 6 am (p = 0.13), whereas, at the non-ICU, 38% of the deaths occurred between 6 am and 12 pm, 18% between 12 pm and 6 pm, 19% between 6 pm and 12 am and 25% between 12 am and 6 am (p = 0.005). CONCLUSION: At the non-ICU, deaths occur more often in the morning period and follow a circadian rhythm, which does not occur at the ICU.