The impact of COVID-19 lockdown on children with recurrent wheezing and asthma in Spain.

AIM: The rapid spread of a novel human coronavirus SARS-CoV-2 led to drastic measures world-wide. Most countries were forced to declare a national lockdown. We studied the effect of lockdown measures on the level of asthma control and maintenance treatment in children with recurrent wheezing and asthma during the first wave of COVID-19 in Spain. METHODS: We analysed children with recurrent wheezing or asthma before and after the implementation of the lockdown, by using a questionnaire aimed to examine pre-existing respiratory disorders, step treatment and level of asthma control before/after lockdown, COVID history and laboratory testing including IgG SARS-CoV-2. RESULTS: We enrolled 475 asthmatic and pre-school wheezers (60.6% males), mean age 5.6 years. There were no differences in asthma treatment comparing both periods: 81.7% maintained the same treatment (P = 0.103). According to child asthma-control questionnaire, 87.7% remained well controlled during confinement. Nearly, a third of children (34.9%) needed reliever treatment, mainly in older children. Determination of IgG SARS-CoV-2 was performed in 233 children (49.1%) of whom 17 (7.3%) tested positive. Seven patients positive to IgG SARS-CoV-2 were assisted in the emergency department and two required hospital admission. CONCLUSIONS: During COVID-19 lockdown in Spain, most children with recurrent wheezing and asthma remained well controlled from their underlying disease and did not modify greatly their maintenance treatments. Unexpectedly, we also observed that those children who tested positive to SARS-CoV-2 IgG showed a significant increase in paediatric hospital admissions and attendances to urgent care settings.

Environmental evaluation of a prefab construction method employed to build the Evandro Chagas National Institute of Infectious Diseases

As a result of the global pandemic of Covid-19, there was a need to adjust to the sanitary tragedy that occurred during this time, which stimulated the construction of emergency support units to support the existing health system. In the study presented in this paper, the authors evaluate the potential environmental impacts of modular typologies through quantification and analysis of carbon emissions of a typical hospitalar module throughout its life cycle. A systematic Life Cycle Assessment analysis was carried out to quantify GHG emissions related to the construction of a module of the Evandro Chagas National Institute of Infectious Diseases in Brazil and understand the benefits of reuse and recycling processes by comparing a single-use scenario to a cradle-to-cradle approach. Another objective is to compare Polyisocyanurate (PIR), Expanded Polystyrene (EPS) and Rock wool when used as insulation, given that their thermal performance is similar but their density influences the impact rates. Overall, EPS panels present a better environmental performance while maintaining thermal comfort standards found in comparison to rock wool and PIR boards. Lastly, concrete for the slab was responsible for the highest emission rates of kg CO2eq/module year, followed by the rigid PIR foam and steel in the production and sanitary landfill disposal stages.

An unusual cause for hypoxemia and breathlessness

Thanks to the author's interest, complementary diagnostic tests were performed and the diagnosis was made. The author also made it possible to treat the patient through contact with the colleagues that performed the procedure. 75-year-old woman with past medical history of ischemic stroke in 2019, when complementary diagnostic tests were performed and it was found that the patient had a patent foramen ovale (PFO). Current hospitalization due to COVID-19 pneumonia, which was complicated by bacterial co-infection and intermediate-low risk right main pulmonary artery thromboembolism. The patient was successfully treated, with improvement of the clinical condition and evident imaging resolution of pulmonary cavitations and recanalization of the right pulmonary artery. However, something intriguing was observed: The patient presented dyspnea in the upright position and a decline in transcutaneous oxygen saturation from 96% in the supine position to 85% in orthostatism, with reversal of these findings with the recumbency. This led to the suspicion of platypnea-orthodeoxia syndrome. A transesophageal echocardiogram with bubble test was then performed, revealing an atrial shunt in the supine position without Valsalva maneuver. With these evidences, the diagnosis of platypnea-orthodeoxia syndrome was made. Even though the patient was >60 years, due to important right-to-left shunt, the history of stroke and the current platypnea-orthodeoxia, it was decided to close the PFO. The day after the procedure, the patient was placed in the upright position, maintaining an oxygen saturation of 96%. This case is an example that the decision of closing PFO must be individualized, not focusing only on patient's age, but also on his medical history and current situation, as indicated in the 2022 Guidelines for the Management of Patent Foramen Ovale. (Figure Presented).

Decrease in CD8+CD45+CCR7+CD62L+ T cells in individuals vaccinated with Sinovac-CoronaVac following COVID-19 infection.

Vaccines induce antibodies, but T cell responses are also important for protection against Coronavirus disease 2019. Here, we analyzed the frequency of memory T cells in infected and/or vaccinated individuals and observed a decrease in central memory T cells in individuals who were vaccinated following COVID-19 infection.

Seroconversion in asymptomatic COVID-19 pediatric patients with rheumatic diseases of one tertiary referral hospital.

OBJECTIVES: To evaluate seroconverted asymptomatic COVID-19 in pediatric Autoimmune Rheumatic Diseases (ARDs) patients and to identify the risk factors related to contagion. METHODS: A cross-sectional study was conducted in March 2021, before vaccination of children and adolescents in Brazil, including 77 pediatric ARDs patients, followed at a tertiary hospital and 45 healthy controls, all of them without a previous diagnosis of COVID-19. Data was obtained by a questionnaire with demographic data, symptoms compatible with COVID-19 over the previous year, and contact with people with confirmed COVID-19. Patient's medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed on all participants. RESULTS: Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p = 0.173), age (14 vs. 13 years, p = 0.269) and SARS-CoV-2 positive serology (22% vs. 15.5%, p = 0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs: 27.3% of them used corticosteroids (33.3% in high doses), and 7.8% on immunobiologicals. No statistical differences were found between positive (n = 17) and negative serology (n = 60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p > 0.05). CONCLUSIONS: Pediatric rheumatic disease patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its immunosuppressive treatment seemed to interfere with contagion risk.

DEVELOPMENT AND VALIDATION OF AN ENZYME-LINKED IMMUNOASSAY KIT FOR DIAGNOSIS AND SURVEILLANCE OF COVID-19.

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-CoV-2 antibodies in human sera with high reliability.

Invasive Meningococcal X Disease during the COVID-19 Pandemic, Brazil.

Invasive meningococcal disease persists as a fulminant disorder worldwide. Although cases caused by Neisseria meningitidis serogroup X (MenX) occur infrequently, outbreaks have been reported in countries in Africa in recent decades. We report 2 cases of MenX invasive meningococcal disease in São Paulo, Brazil, in 2021 and 2022, during the COVID-19 pandemic.

Tracking the turnover of SARS-CoV-2 VOCs Gamma to Delta in a Brazilian state (Minas Gerais) with a high-vaccination status.

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

COVID-19 Vaccination Intentions amongst Healthcare Workers: A Scoping Review.

A worldwide vaccination programme is the chosen strategy against the COVID-19 pandemic. Vaccine hesitancy, however, forms a threat to achieving a high degree of vaccination. Healthcare workers (HCWs) are exposed to greater risks, in addition to HCWs who care for people with intellectual disabilities (ID). However, little is still known about these groups' vaccine hesitancy. This review aims to provide insight into the intentions and attitudes of HCWs on COVID-19 vaccination, including those who care for people with ID. The search included both types and was conducted in nine databases. A total of 26 papers were identified concerning the vaccine intentions of 43,199 HCWs worldwide. The data were gathered both quantitively and qualitatively. The papers were analysed for all of the themes regarding vaccine intentions, which were: (1) percentages of vaccine willingness; (2) predictors of willingness; (3) attitudes of willingness and hesitancy; (4) sources of vaccination information; (5) contextual factors and changes in COVID-19 vaccine acceptance over time; and (6) future strategies for interventions. Concerns about vaccine safety, efficacy and short- and long-term side effects were the most prominent in HCWs and, therefore, should be addressed in future intervention strategies. Furthermore, interactive interventions are recommended to facilitate exchange, and accurate information should be accessible to target groups on social media platforms.

Development and validation of an enzyme-linked immunoassay kit for diagnosis and surveillance of COVID-19.

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-CoV-2 antibodies in human sera with high reliability.

Bovine Coronavirus Co-infection and Molecular Characterization in Dairy Calves With or Without Clinical Respiratory Disease.

Bovine respiratory disease (BRD) is considered a major cause of morbidity and mortality in young calves and is caused by a range of infectious agents, including viruses and bacteria. This study aimed to determine the frequency of viral and bacterial pathogens detected in calves with BRD from high-production dairy cattle herds and to perform the molecular characterization of N and S1 genes in identified bovine coronavirus (BCoV) strains. Nasal swabs were collected from 166 heifer calves, namely, 85 symptomatic and 81 asymptomatic calves aged between 5 and 90 days, from 10 dairy cattle herds. Nasal swabs were evaluated using molecular techniques for the identification of viruses (BCoV, bovine alphaherpesvirus 1, bovine viral diarrhea virus, bovine parainfluenza virus 3, and bovine respiratory syncytial virus) and bacteria (Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, and Mycoplasma bovis). In addition, five and two BCoV-positive samples were submitted to N and S1 gene amplification and nucleotide sequencing, respectively. The frequency of diagnosis of BCoV was higher (56%, 93/166) than the frequency of P. multocida (39.8%, 66/166) and M. haemolytica (33.1%, 55/166). The three microorganisms were identified in the calves of symptomatic and asymptomatic heifer calve groups. All other pathogens included in the analyses were negative. In the phylogenetic analysis of the S1 gene, the Brazilian strains formed a new branch, suggesting a new genotype, called # 15; from the N gene, the strains identified here belonged to cluster II. This study describes high rates of BCoV, P. multocida, and M. haemolytica in heifer calves from high-production dairy cattle herds with BRD. Additionally, the molecular characterization provides evidence that the circulating BCoV strains are ancestrally different from the prototype vaccine strains and even different BCoV strains previously described in Brazil.

Long-Acting Injectable Antipsychotics (LAIs) Prescribing Trends during the COVID-19 Pandemic in Romania.

Long acting injectable antipsychotics (LAIs) are considered the ideal treatment for schizophrenia, especially for young patients with high rates of non-adherence. In the current COVID-19 pandemic, it has been reported that the administration of LAIs decreased in some areas. The aim of this study was to evaluate the impact of COVID-19 pandemic on the initiation of LAIs. This is a retrospective mirror- image study covering a total period of 24 months: 12 months before and 12 months after the declaration of COVID-19 pandemic on March 11, 2020. During the study period, out of 218 patients admitted with schizophrenia, only 15 (1.3%) received LAIs at discharge. There was a 48.3% reduction in LAIs initiation compared to the pre-pandemic period (29 LAIs initiations in 2019 from 224 admissions). Despite the 27% reduction in the total number of admissions (1500 in 2019 vs. 1100 in 2020), the number of admissions with schizophrenia remained almost the same (224 in 2019 vs. 218 in 2020). COVID-19 pandemic brought an important challenge in the treatment of patients with schizophrenia, especially in the initiation of LAIs. This could have an important impact on the relapse rate in the next period.

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice.

In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8+ T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice.

An Exploratory Study among Intellectual Disability Physicians on the Care and Coercion Act and the Use of Psychotropic Drugs for Challenging Behaviour.

The new Dutch Care and Coercion Act aims to better regulate the use of psychotropic drugs for challenging behaviour in people with an intellectual disability. This study explores experiences of intellectual disability physicians (IDPs) in prescribing psychotropic drugs and investigates how the Act and the new multidisciplinary guideline on challenging behaviour affects their practice. A qualitative study was conducted, consisting of nine semi-structured in-depth interviews with IDPs, followed by a thematic analysis. It was found that IDPs experienced the new Act and guideline as supportive of their work as guardians of the appropriate use of psychotropic drugs. The multidisciplinary character of the guideline was experienced positively. However, IDPs are faced with organisational barriers and time constraints, as such, they question the feasibility of implementing the Act. Based on these findings, it can be concluded that the Care and Coercion Act may support the existing shift towards the appropriate use of psychotropic drugs if required conditions can be met.

Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients.

For over a year, the coronavirus disease 2019 has been affecting the world population by causing severe tissue injuries and death in infected people. Adenosine triphosphate (ATP) and the nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct virus infection or cell death caused by hyper inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pathway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed raw proteomics data acquired using mass spectrometry (the gold standard method) and raw genomics data from COVID-19 patient samples obtained by microarray. The data was analyzed using bioinformatics and statistical methods according to our objectives. Here, we compared the purinergic profile of the total leukocyte population and evaluated the levels of these soluble biomolecules in the blood, and their correlation with coagulation components in COVID-19 patients, in comparison to healthy people or non-COVID-19 patients. The blood metabolite analysis showed a stage-dependent inosine increase in COVID-19 patients, while the nucleotides ATP and ADP had positive correlations with fibrinogen and other coagulation proteins. Also, ATP, ADP, inosine, and hypoxanthine had positive and negative correlations with clinical features. Regarding leukocyte gene expression, COVID-19 patients showed an upregulation of the P2RX1, P2RX4, P2RX5, P2RX7, P2RY1, P2RY12, PANX1, ADORA2B, NLPR3, and F3 genes. Yet, the ectoenzymes of the canonical and non-canonical adenosinergic pathway (ENTPD1 and CD38) are upregulated, suggesting that adenosine is produced by both active adenosinergic pathways. Hence, approaches targeting these biomolecules or their specific purinoreceptors and ectoenzymes may attenuate the high inflammatory state and the coagulopathy seen in COVID-19 patients. KEY MESSAGES : Adenosinergic pathways are modulated on leukocytes from COVID-19 patients. Plasmatic inosine levels are increased in COVID-19 patients. ATP, ADP, AMP, hypoxanthine, and inosine are correlated with coagulation players. The nucleotides and nucleosides are correlated with patients' clinical features. The P2 receptors and ectoenzymes are correlated with Tissue factor in COVID-19.

Implications of COVID-19 Regulations for People With Visual and Intellectual Disabilities: Lessons to Learn From Visiting Restrictions.

Background: Due to the COVID-19 pandemic, governments of many countries announced regulations to prevent the virus from spreading. For people with a disability living in a sheltered care facility in the Netherlands, this meant that they were not able to receive any visitors for almost 3 months. Aim: This study examines how people with an intellectual and visual disability and their families experienced the period in which it was mandated not to have any physical contact. The aim is to examine the experiences of this target group and gain insight in the way measures were taken in order to be able to advise care organizations about adequate care with respect to possible restrictive measures in the future. Methods: In-depth interviews were conducted with two groups of people: (1) fourteen people with an intellectual and visual disability, living in sheltered care facilities and (2) twelve people being relatives of residents of these same sheltered care facilities. In the interviews, the participants were questioned about their experiences with respect to the adjusted visiting regulations and with respect to the relation with their family during this period. A thematic analysis was performed first separately and then combined. Results and Discussion: A number of themes resulted from the analysis that were related to (1) the instructed regulations of the sheltered care facilities and the government; (2) the relation with family and friends; and (3) the consequences of COVID-19 and the regulations. Both relatives and residents were understanding of the difficult situation, but also expressed criticism about the chosen regulations, the communication thereof, and the practical implementation. Both groups have experienced the interruption of close contact as emotional and difficult. However, also positive consequences of the restrictions due to COVID-19 were mentioned. The results provide a list of recommendations for sheltered care facilities.