Social distancing, emotional suffering, and cognitive performance in mature and older adults: a literature review.

Variables related to social distancing can have negative effects on the emotional well-being and cognition of adults and the elderly. Objective: The aim of this study was to analyze the available studies that address the relationship between situations of social distancing, socioemotional aspects, and cognition in the lives of mature and older adults. Methods: A literature review study was carried out between December 2021 and January 2022, involving the SciELO, PubMed, and ScienceDirect databases, with studies published between February 2018 and December 2021. Results: A total of 754 studies were identified, and after selection, 18 were included. Notably, 16 showed significant effects of social distancing on cognition and socioemotional aspects, that is, the greater the social distancing, the lower the capacity for cognitive performance and the higher the index of symptoms of depression and anxiety, for example. Conclusions: Greater engagement in social activities and a closer contact with friends and family are protective factors against symptoms of depression and anxiety and cognitive decline.

Variáveis relacionadas ao distanciamento social podem gerar efeitos negativos para o bem-estar emocional e para a cognição de adultos e idosos. Objetivo: Analisar os estudos disponíveis que abordam a relação entre situações de distanciamento social, sofrimento emocional e cognição na vida de adultos maduros e idosos. Métodos: Realizou-se um estudo de revisão de literatura entre dezembro de 2021 e janeiro de 2022, que envolveu as bases de dados Scientific Electronic Library Online (SciELO), United States National Library of Medicine (PubMed) e ScienceDirect, com estudos publicados entre fevereiro de 2018 a dezembro de 2021. Resultados: O total de 754 trabalhos foi identificado e, após a seleção, 18 foram incluídos. Dezesseis mostraram efeitos significativos do distanciamento social na cognição e no sofrimento emocional, ou seja, quanto maior o distanciamento social, menor a capacidade de desempenho cognitivo e maior o índice de sintomas de depressão e ansiedade, por exemplo. Conclusões: O maior engajamento em atividades sociais e a maior aproximação com amigos e familiares são fatores de proteção contra sintomas de depressão e ansiedade e declínio cognitivo.

Comparison of diagnostic performance of RT-qPCR, RT-LAMP and IgM/IgG rapid tests for detection of SARS-CoV-2 among healthcare workers in Brazil.

BACKGROUND: COVID-19 has become a major public health problem after the outbreak caused by SARS-CoV-2 virus. Great efforts to contain COVID-19 transmission have been applied worldwide. In this context, accurate and fast diagnosis is essential. METHODS: In this prospective study, we evaluated the clinical performance of three different RNA-based molecular tests - RT-qPCR (Charité protocol), RT-qPCR (CDC (USA) protocol) and RT-LAMP - and one rapid test for detecting anti-SARS-CoV-2 IgM and IgG antibodies. RESULTS: Our results demonstrate that RT-qPCR using the CDC (USA) protocol is the most accurate diagnostic test among those evaluated, while oro-nasopharyngeal swabs are the most appropriate biological sample. RT-LAMP was the RNA-based molecular test with lowest sensitivity while the serological test presented the lowest sensitivity among all evaluated tests, indicating that the latter test is not a good predictor of disease in the first days after symptoms onset. Additionally, we observed higher viral load in individuals who reported more than 3 symptoms at the baseline. Nevertheless, viral load had not impacted the probability of testing positive for SARS-CoV-2. CONCLUSION: Our data indicates that RT-qPCR using the CDC (USA) protocol in oro-nasopharyngeal swabs samples should be the method of choice to diagnosis COVID-19.

Subjective impacts of computerized cognitive training for healthy older adults in the context of the COVID-19 pandemic.

BACKGROUND: Computerized cognitive training programs may have benefited the self-assessment of memory, quality of life, and mood among older adults during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To determine the subjective impacts of computerized cognitive training on mood, frequency of forgetfulness, memory complaints, and quality of life in the elderly using an online platform. METHODS: In total, 66 elderly participants of USP 60 + , a program for the elderly offered by Universidade de São Paulo, who voluntarily enrolled in the study were selected and randomized with an allocation ratio of 1:1 into 2 groups: the training group (n = 33) and the control group (n = 33). After signing the free and informed consent form, they answered a protocol which included a sociodemographic questionnaire, the Memory Complaints Questionnaire (MAC-Q), the McNair and Kahn's Frequency of Forgetfulness Scale, the Geriatric Depression Scale (GDS-15), the Geriatric Anxiety Inventory (GAI), and the Control, Autonomy, Self-Realization, and Pleasure (CASP-19) questionnaire. The training cognitive game platform aimed to stimulate various cognitive aspects, including memory, attention, language, executive functions (reasoning, logical thinking), and visual and spatial skills. RESULTS: The participants of the training group showed a reduction in the MAC-Q, MacNair and Kahn, and GAI scores in the pre- and posttest comparison. Significant differences were identified between the groups regarding the total scores of the MAC-Q in the post-test, which was also evidenced by the logistic regression. CONCLUSION: Participation in a computerized cognitive intervention promoted reductions in memory complaints, frequency of forgetfulness, and anxiety symptoms, in addition to improving self-reported quality of life.

ANTECEDENTES: Programas informatizados de treinamento cognitivo podem ter beneficiado a autoavaliação da memória, a qualidade de vida e o humor entre os idosos durante a pandemia de doença do coronavírus 2019 (coronavirus disease 2019, COVID-19, em inglês). OBJETIVO: Determinar os impactos subjetivos do treinamento cognitivo computadorizado no humor, na frequência de esquecimento, nas queixas de memória, e na qualidade de vida em idosos utilizando uma plataforma online. MéTODOS: Ao todo, 66 idosos participantes do programa USP 60 + , oferecido à terceira idade pela Universidade de São Paulo, e inscritos voluntariamente no estudo, foram selecionados e randomizados em uma razão de 1:1 em 2 grupos: grupo treinamento (n = 33) e grupo controle (n = 33). Após assinarem o termo de consentimento livre e esclarecido, os participantes responderam a um protocolo que incluía um questionário sociodemográfico, o Questionário de Queixas de Memória (Memory Complaints Questionnaire, MAC-Q), A Escala de Frequência de Esquecimento de McNair e Kahn, a Escala de Depressão Geriátrica (Geriatric Depression Scale, GDS-15), o Inventário de Ansiedade Geriátrica (Geriatric Anxiety Inventory, GAI), e ­o questionário de Controle, Autonomia, Autorrealização e Prazer (Control, Autonomy, Self-Realization, and Pleasure, CASP-19). A plataforma de jogos cognitivos de treinamento visou estimular diversos aspectos cognitivos, incluindo memória, atenção, linguagem, funções executivas (raciocínio, raciocínio lógico) e habilidades visuais e espaciais. RESULTADOS: Na comparação pré e pós-teste, os participantes do grupo de treinamento apresentaram redução nas pontuações do MAC-Q, da escala McNair e Kahn e do GAI. Diferenças significativas entre os grupos quanto às pontuações totais da escala MAC-Q no pós-teste também foram evidenciadas pela regressão logística. CONCLUSãO: A participação em uma intervenção cognitiva computadorizada promoveu reduções nas queixas de memória, frequência de esquecimento e sintomas de ansiedade, além de melhorar a qualidade de vida autorrelatada.

Molecular characterization of a new SARS-CoV-2 recombinant cluster XAG identified in Brazil.

Recombination events have been described in the Coronaviridae family. Since the beginning of the SARS-CoV-2 pandemic, a variable degree of selection pressure has acted upon the virus, generating new strains with increased fitness in terms of viral transmission and antibody scape. Most of the SC2 variants of concern (VOC) detected so far carry a combination of key amino acid changes and indels. Recombination may also reshuffle existing genetic profiles of distinct strains, potentially giving origin to recombinant strains with altered phenotypes. However, co-infection and recombination events are challenging to detect and require in-depth curation of assembled genomes and sequencing reds. Here, we present the molecular characterization of a new SARS-CoV-2 recombinant between BA.1.1 and BA.2.23 Omicron lineages identified in Brazil. We characterized four mutations that had not been previously described in any of the recombinants already identified worldwide and described the likely breaking points. Moreover, through phylogenetic analysis, we showed that the newly named XAG lineage groups in a highly supported monophyletic clade confirmed its common evolutionary history from parental Omicron lineages and other recombinants already described. These observations were only possible thanks to the joint effort of bioinformatics tools auxiliary in genomic surveillance and the manual curation of experienced personnel, demonstrating the importance of genetic, and bioinformatic knowledge in genomics.

The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.

The turning point of COVID-19 severity is associated with a unique circulating neutrophil gene signature.

COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation.

Immunogenicity, Effectiveness, and Safety of Inactivated Virus (CoronaVac) Vaccine in a Two-Dose Primary Protocol and BNT162b2 Heterologous Booster in Brazil (Immunita-001): A One Year Period Follow Up Phase 4 Study.

Background: Effective and safe vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical to controlling the COVID-19 pandemic and will remain the most important tool in limiting the spread of the virus long after the pandemic is over. Methods: We bring pioneering contributions on the maintenance of the immune response over a year on a real-life basis study in 1,587 individuals (18-90 yrs, median 39 yrs; 1,208 female/379 male) who underwent vaccination with two doses of CoronaVac and BNT162b2 booster after 6-months of primary protocol. Findings: Elevated levels of anti-spike IgG antibodies were detected after CoronaVac vaccination, which significantly decreased after 80 days and remained stable until the introduction of the booster dose. Heterologous booster restored antibody titers up to-1·7-fold, changing overall seropositivity to 96%. Titers of neutralising antibodies to the Omicron variant were lower in all timepoints than those against Delta variant. Individuals presenting neutralising antibodies against Omicron also presented the highest titers against Delta and anti-Spike IgG. Cellular immune response measurement pointed out a mixed immune profile with a robust release of chemokines, cytokines, and growth factors on the first month after CoronaVac vaccination followed by a gradual reduction over time and no increase after the booster dose. A stronger interaction between those mediators was noted over time. Prior exposure to the virus leaded to a more robust cellular immune response and a rise in antibody levels 60 days post CoronaVac than in individuals with no previous COVID-19. Both vaccines were safe and well tolerated among individuals. Interpretation: Our data approach the effectiveness of CoronaVac association with BNT162b2 from the clinical and biological perspectives, aspects that have important implications for informing decisions about vaccine boosters. Funding: Fiocruz, Brazil.

Molecular characterization of a new SARS-CoV-2 recombinant cluster XAG identified in Brazil

Recombination events have been described in the Coronaviridae family. Since the beginning of the SARS-CoV-2 pandemic, a variable degree of selection pressure has acted upon the virus, generating new strains with increased fitness in terms of viral transmission and antibody scape. Most of the SC2 variants of concern (VOC) detected so far carry a combination of key amino acid changes and indels. Recombination may also reshuffle existing genetic profiles of distinct strains, potentially giving origin to recombinant strains with altered phenotypes. However, co-infection and recombination events are challenging to detect and require in-depth curation of assembled genomes and sequencing reds. Here, we present the molecular characterization of a new SARS-CoV-2 recombinant between BA.1.1 and BA.2.23 Omicron lineages identified in Brazil. We characterized four mutations that had not been previously described in any of the recombinants already identified worldwide and described the likely breaking points. Moreover, through phylogenetic analysis, we showed that the newly named XAG lineage groups in a highly supported monophyletic clade confirmed its common evolutionary history from parental Omicron lineages and other recombinants already described. These observations were only possible thanks to the joint effort of bioinformatics tools auxiliary in genomic surveillance and the manual curation of experienced personnel, demonstrating the importance of genetic, and bioinformatic knowledge in genomics.

A value chain development model for the public sector

Purpose The value chain is an essential management tool for the elaboration of strategic organizational planning. However, there are few published works providing methods for the development of value chains. This research aims to present a model to develop the value chain for the public sector. Design/methodology/approach Action research was used with case study in the evaluation step. Findings This research presents a model for value chain development along seven steps, covering data collection planning to the formalization of final product acceptance. The model suggests executing these seven steps in three iteration levels: operational, tactical and strategic. Through case studies, six practical insights were also highlighted in this work. Research limitations/implications Given the absence of related work, one of the limitations is the lack of comparison with other methods of value chain development in the public sector. Originality/value There are practical guides to value chain development in the public sector;however, to the best of authors' knowledge, such guides have not been developed using research methods. In the literature, no works provide details on how value chain can be developed in the public sector. In addition, the constraints of face-to-face contacts during the COVID-19 pandemic led the research team to conduct remotely the model's development and evaluation in the case studies. The model presents elements that enable value chain development without face-to-face contact between the execution team and public institution's stakeholders.

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule.

The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.

Celastrol: A lead compound that inhibits SARS-CoV-2 replication, the activity of viral and human cysteine proteases, and virus-induced IL-6 secretion.

The global emergence of coronavirus disease 2019 (COVID-19) has caused substantial human casualties. Clinical manifestations of this disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and hyperinflammation. In face of the urgent demand for effective drugs to treat COVID-19, we have searched for candidate compounds using in silico approach followed by experimental validation. Here we identified celastrol, a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F, as one of the best compounds out of 39 drug candidates. Celastrol reverted the gene expression signature from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells and irreversibly inhibited the recombinant forms of the viral and human cysteine proteases involved in virus invasion, such as Mpro (main protease), PLpro (papain-like protease), and recombinant human cathepsin L. Celastrol suppressed SARS-CoV-2 replication in human and monkey cell lines and decreased interleukin-6 (IL-6) secretion in the SARS-CoV-2-infected human cell line. Celastrol acted in a concentration-dependent manner, with undetectable signs of cytotoxicity, and inhibited in vitro replication of the parental and SARS-CoV-2 variant. Therefore, celastrol is a promising lead compound to develop new drug candidates to face COVID-19 due to its ability to suppress SARS-CoV-2 replication and IL-6 production in infected cells.

Mitochondrial DNA and TLR9 activation contribute to SARS-CoV-2-induced endothelial cell damage.

BACKGROUND AND PURPOSE: Mitochondria play a central role in the host response to viral infection and immunity, being key to antiviral signaling and exacerbating inflammatory processes. Mitochondria and Toll-like receptor (TLR) have been suggested as potential targets in SARS-CoV-2 infection. However, the involvement of TLR9 in SARS-Cov-2-induced endothelial dysfunction and potential contribution to cardiovascular complications in COVID-19 have not been demonstrated. This study determined whether infection of endothelial cells by SARS-CoV-2 affects mitochondrial function and induces mitochondrial DNA (mtDNA) release. We also questioned whether TLR9 signaling mediates the inflammatory responses induced by SARS-CoV-2 in endothelial cells. EXPERIMENTAL APPROACH: Human umbilical vein endothelial cells (HUVECs) were infected by SARS-CoV-2 and immunofluorescence was used to confirm the infection. Mitochondrial function was analyzed by specific probes and mtDNA levels by real-time polymerase chain reaction (RT-PCR). Inflammatory markers were measured by ELISA, protein expression by western blot, intracellular calcium (Ca2+) by FLUOR-4, and vascular reactivity with a myography. KEY RESULTS: SARS-CoV-2 infected HUVECs, which express ACE2 and TMPRSS2 proteins, and promoted mitochondrial dysfunction, i.e. it increased mitochondria-derived superoxide anion, mitochondrial membrane potential, and mtDNA release, leading to activation of TLR9 and NF-kB, and release of cytokines. SARS-CoV-2 also decreased nitric oxide synthase (eNOS) expression and inhibited Ca2+ responses in endothelial cells. TLR9 blockade reduced SARS-CoV-2-induced IL-6 release and prevented decreased eNOS expression. mtDNA increased vascular reactivity to endothelin-1 (ET-1) in arteries from wild type, but not TLR9 knockout mice. These events were recapitulated in serum samples from COVID-19 patients, that exhibited increased levels of mtDNA compared to sex- and age-matched healthy subjects and patients with comorbidities. CONCLUSION AND APPLICATIONS: SARS-CoV-2 infection impairs mitochondrial function and activates TLR9 signaling in endothelial cells. TLR9 triggers inflammatory responses that lead to endothelial cell dysfunction, potentially contributing to the severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathways may help to define novel therapeutic strategies for COVID-19.

Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells.

COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV-2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppresses macrophage anti-inflammation and efficient tissue repair programs and provides mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.

Booster dose of BNT162b2 after two doses of CoronaVac improves neutralization of SARS-CoV-2 Omicron variant.

Background: The emergence of the new SARS-CoV-2 Omicron variant, which is known to have a large number of mutations when compared to other variants, brought to light the concern about vaccine escape, especially from the neutralization by antibodies induced by vaccination. Methods: Based on viral microneutralization assays, we evaluated in 90 individuals the impact on antibody neutralization induction, against Omicron variant, by a booster dose of BNT162b2 mRNA vaccine after the CoronaVac primary vaccination scheme. Results: Here we show that the percentage of seroconverted individuals 30 and 60 days after CoronaVac scheme was 16.6% and 10%, respectively. After booster dose administration, the seroconvertion rate increased to 76.6%. The neutralization mean titer against Omicron in the CoronaVac protocol decreased over time, but after the booster dose, the mean titer increased 43.1 times. Conclusions: These results indicate a positive impact of this vaccine combination in the serological immune response against SARS-CoV-2 Omicron variant.

Acetylcholine, Fatty Acids, and Lipid Mediators Are Linked to COVID-19 Severity.

Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, 11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE2, thromboxane B2, 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid, and 6-trans-leukotriene B4 Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1ß, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.

Molecular detection of omicron SARS-CoV-2 variant is achieved by RT-LAMP despite genomic mutations.

BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron variant was first detected in South Africa in November 2021. Since then, the number of cases due to this variant increases enormously every day in different parts of the world. Mutations within omicron genome may impair the molecular detection resulting in false negative results during Coronavirus disease 19 (COVID-19) diagnosis. OBJECTIVES: To verify if colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) targeting N and E genes would work efficiently to detect omicron SARS-CoV-2 variant and its sub-lineages. METHODS: SARS-CoV-2 reverse transcription quantitative polymerase chain reaction (RT-qPCR) positive samples were sequenced by next generation DNA sequencing. The consensus sequences generated were submitted to Pangolin tool for SARS-CoV-2 lineage identification. RT-LAMP reactions were performed at 65ºC/30 min targeting N and E. FINDINGS: SARS-CoV-2 omicron can be detected by RT-LAMP targeting N and E genes despite the genomic mutation of this more transmissible lineage. Omicron SARS-CoV-2 sub-lineages were tested and efficiently detected by RT-LAMP. We demonstrated that this test is very sensitive in detecting omicron variant, with LoD as low as 0.4 copies/µL. MAIN CONCLUSIONS: Molecular detection of omicron SARS-CoV-2 variant and its sub-lineages can be achieved by RT-LAMP despite the genomic mutations as a very sensitive surveillance tool for COVID-19 molecular diagnosis.

Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients.

In the present study, the levels of serum and airway soluble chemokines, pro-inflammatory/regulatory cytokines, and growth factors were quantified in critically ill COVID-19 patients (total n=286) at distinct time points (D0, D2-6, D7, D8-13 and D>14-36) upon Intensive Care Unit (ICU) admission. Augmented levels of soluble mediators were observed in serum from COVID-19 patients who progress to death. An opposite profile was observed in tracheal aspirate samples, indicating that systemic and airway microenvironment diverge in their inflammatory milieu. While a bimodal distribution was observed in the serum samples, a unimodal peak around D7 was found for most soluble mediators in tracheal aspirate samples. Systems biology tools further demonstrated that COVID-19 display distinct eccentric soluble mediator networks as compared to controls, with opposite profiles in serum and tracheal aspirates. Regardless the systemic-compartmentalized microenvironment, networks from patients progressing to death were linked to a pro-inflammatory/growth factor-rich, highly integrated center. Conversely, patients evolving to discharge exhibited networks of weak central architecture, with lower number of neighborhood connections and clusters of pro-inflammatory and regulatory cytokines. All in all, this investigation with robust sample size landed a comprehensive snapshot of the systemic and local divergencies composed of distinct immune responses driven by SARS-CoV-2 early on severe COVID-19.

Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress.

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.

The enzymes in COVID-19: A review.

COVID-19 brought a scientific revolution since its emergence in Wuhan, China, in December 2019. Initially, the SARS-CoV-2 virus came to attention through its effects on the respiratory system. However, its actions in many other organs also have been discovered almost daily. As enzymes are indispensable to uncountable biochemical reactions in the human body, it is not surprising that some enzymes are of relevance to COVID-19 pathophysiology. Past evidence from SARS-CoV and MERS-CoV outbreaks provided hints about the role of enzymes in SARS-CoV-2 infection. In this setting, ACE-2 is an enzyme of great importance since it is the cell entry receptor for SARS-CoV-2. Clinical data elucidate patterns of enzymatic alterations in COVID-19, which could be associated with organ damage, prognosis, and clinical complications. Further, viral mutations can create new disease behaviors, and these effects are related to the activity of enzymes. This review will discuss the main enzymes related to COVID-19, summarizing the findings on their role in viral entry mechanism, the consequences of their dysregulation, and the effects of SARS-CoV-2 mutations on them.