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1.
Artigo em Inglês | MEDLINE | ID: mdl-34753828

RESUMO

BACKGROUND AND OBJECTIVES: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS. METHODS: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity. RESULTS: In 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction. DISCUSSION: SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/imunologia , Imunogenicidade da Vacina/imunologia , Esclerose Múltipla/complicações , Esclerose Múltipla/imunologia , Adulto , Idoso , COVID-19/prevenção & controle , COVID-19/virologia , Estudos Transversais , Feminino , Humanos , Imunização Secundária/efeitos adversos , Internet , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/virologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Inquéritos e Questionários , Vacinação/efeitos adversos , Vacinação/estatística & dados numéricos
2.
Artigo em Inglês | MEDLINE | ID: mdl-34759018

RESUMO

BACKGROUND AND OBJECTIVES: To investigate whether children receiving immunosuppressive therapies for neuroimmunologic disorders had (1) increased susceptibility to SARS-CoV2 infection or to develop more severe forms of COVID-19; (2) increased relapses or autoimmune complications if infected; and (3) changes in health care delivery during the pandemic. METHODS: Patients with and without immunosuppressive treatment were recruited to participate in a retrospective survey evaluating the period from March 14, 2020, to March 30, 2021. Demographics, clinical features, type of immunosuppressive treatment, suspected or confirmed COVID-19 in the patients or cohabitants, and changes in care delivery were recorded. RESULTS: One hundred fifty-three children were included: 84 (55%) female, median age 13 years (interquartile range [8-16] years), 79 (52%) on immunosuppressive treatment. COVID-19 was suspected or confirmed in 17 (11%) (all mild), with a frequency similar in patients with and without immunosuppressive treatment (11/79 [14%] vs 6/74 [8%], p = 0.3085). The frequency of neurologic relapses was similar in patients with (18%) and without (21%) COVID-19. Factors associated with COVID-19 included having cohabitants with COVID-19 (p < 0.001) and lower blood levels of vitamin D (p = 0.039). Return to face-to-face schooling or mask type did not influence the risk of infection, although 43(28%) children had contact with a classmate with COVID-19. Clinic visits changed from face to face to remote for 120 (79%) patients; 110 (92%) were satisfied with the change. DISCUSSION: In this cohort of children with neuroimmunologic disorders, the frequency of COVID-19 was low and not affected by immunosuppressive therapies. The main risk factors for developing COVID-19 were having cohabitants with COVID-19 and low vitamin D levels.


Assuntos
COVID-19/complicações , COVID-19/imunologia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/imunologia , SARS-CoV-2/imunologia , Adolescente , COVID-19/prevenção & controle , COVID-19/virologia , Criança , Atenção à Saúde/organização & administração , Atenção à Saúde/estatística & dados numéricos , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Máscaras/estatística & dados numéricos , Máscaras/virologia , Doenças do Sistema Nervoso/virologia , Pandemias , Recidiva , Estudos Retrospectivos , Vitamina D/sangue
3.
Food Microbiol ; 101: 103890, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34579849

RESUMO

Seroprevalence data for Toxoplasma gondii and Hepatitis E virus (HEV) in wild boar (Sus scrofa), roe deer (Capreolus capreolus), red deer (Cervus elaphus), mouflon (Ovis aries/musimon) and chamois (Rupicapra rupicapra) hunted/culled in northern Italy were used to fit seroprevalence distributions describing the exposure and co-exposure of the species to the two pathogens. The higher proportion of T. gondii and HEV seropositive animals was observed in wild boars with point estimate seroprevalence of 49% (N = 331) and 15% (N = 326) respectively. Data allowed comparisons by area (pre-Alpine Vs Alpine environment) for roe deer, red deer and mouflons. Contrasts between the distributions describing the uncertainty in seroprevalence suggest roe deer, red deer and mouflons have higher probability of being seropositive to T. gondii in pre-Alps. When considering HEV, few seropositive animals were detected and contrasts were symmetrically centred to zero for roe deer and red deer; mouflons shown higher probability of being seropositive in Alpine environment. HEV seropositive animals also included chamois (P = 5.1%, N = 97) in the Alpine districts, confirming circulation of HEV in remote areas. Evidence of HEV and T. gondii co-exposure was limited except for wild boars where it was observed in 30 samples representing 60% of the overall HEV-positive samples. Seroprevalence data of single infection and co-infection are extremely useful to investigate circulation of zoonotic pathogens in wild animals and estimate the foodborne risk of human exposure, however, these type of data do not directly translate into the presence/absence of the pathogen in seropositive and seronegative animals. At benefit of future development of quantitative risk assessments aiming at estimating the risk of human infection/co-infection via consumption of game meat, we developed and made available an online application that allows estimating the probability of the pathogen(s) being present as a function of seroprevalence data.


Assuntos
Cervos , Vírus da Hepatite E , Sus scrofa , Toxoplasma , Toxoplasmose Animal , Animais , Animais Selvagens , Coinfecção/veterinária , Cervos/parasitologia , Cervos/virologia , Doenças Transmitidas por Alimentos , Humanos , Itália , Carne/parasitologia , Carne/virologia , Estudos Soroepidemiológicos , Sus scrofa/parasitologia , Sus scrofa/virologia , Toxoplasmose Animal/epidemiologia
4.
J Med Virol ; 94(1): 7-10, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506635

RESUMO

Hepatitis, a significant cause of mortality worldwide, results in around 1.34 million deaths each year globally. Africa is not exempt from the plague of Hepatitis. Around 100 million estimated individuals are infected with Hepatitis B or C. Egypt has the highest prevalence of cases of Hepatitis followed by Cameroon and Burundi. The continent is severely affected by the onset of the COVID-19 pandemic, as the virus has added an additional burden on the already fragile continent. With the pandemic, it is presumable that Hepatitis like other viral diseases will pose a threat to collapsing healthcare system. Therefore, for Africa to become more resilient in the face of such menaces, including Hepatitis, further prevention policies are required to be implemented.


Assuntos
COVID-19/epidemiologia , Acesso aos Serviços de Saúde , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Países em Desenvolvimento , Egito/epidemiologia , Hepacivirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/terapia , Hepatite C Crônica/prevenção & controle , Hepatite C Crônica/terapia , Humanos , Fígado/lesões , Fígado/patologia , Fígado/virologia , Prevalência , SARS-CoV-2
5.
J Med Virol ; 94(1): 327-334, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524690

RESUMO

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in COVID-19 pandemic control and elimination efforts, especially by elucidating its global transmission network and illustrating its viral evolution. The deployment of multiplex PCR assays that target SARS-CoV-2 followed by either massively parallel or nanopore sequencing is a widely-used strategy to obtain genome sequences from primary samples. However, multiplex PCR-based sequencing carries an inherent bias of sequencing depth among different amplicons, which may cause uneven coverage. Here we developed a two-pool, long-amplicon 36-plex PCR primer panel with ~1000-bp amplicon lengths for full-genome sequencing of SARS-CoV-2. We validated the panel by assessing nasopharyngeal swab samples with a <30 quantitative reverse transcription PCR cycle threshold value and found that ≥90% of viral genomes could be covered with high sequencing depths (≥20% mean depth). In comparison, the widely-used ARTIC panel yielded 79%-88% high-depth genome regions. We estimated that ~5 Mbp nanopore sequencing data may ensure a >95% viral genome coverage with a ≥10-fold depth and may generate reliable genomes at consensus sequence levels. Nanopore sequencing yielded false-positive variations with frequencies of supporting reads <0.8, and the sequencing errors mostly occurred on the 5' or 3' ends of reads. Thus, nanopore sequencing could not elucidate intra-host viral diversity.


Assuntos
Genoma Viral/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Sequenciamento por Nanoporos/métodos , SARS-CoV-2/genética , Sequenciamento Completo do Genoma/métodos , COVID-19 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Nasofaringe/virologia , RNA Viral/genética , Análise de Sequência de RNA/métodos
6.
J Med Virol ; 94(1): 417-423, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34581458

RESUMO

A 36-year-old male with diffuse large B-cell lymphoma on maintenance rituximab therapy presented to the emergency department with high fever and fatigue. A chest X-ray showed a lobar infiltrate, 40 days before admission the patient suffered from a mild coronavirus disease 2019 (COVID-19) infection and fully recovered. PCR nasopharyngeal swab was negative for COVID-19. Comprehensive biochemical, radiological, and pathological evaluation including 18-fluorodeoxyglucose positron emission tomography with computed tomography and transbronchial lung biopsy found no pathogen or lymphoma recurrence. Treatment for pneumonia with antibiotic and antifungal agents was nonbeneficial. A diagnosis of secondary organizing pneumonia (OP) was made after pneumonia migration and a rapid response to corticosteroids. OP secondary to a viral respiratory infection has been well described. Raising awareness for post-COVID-19 OP has therapeutic and prognostic importance because those patients benefit from steroid therapy. We believe the condition described here is underdiagnosed and undertreated by doctors worldwide. Because of the ongoing global pandemic we are now encountering a new kind of patient, patients that have recovered from COVID-19. We hope that this case may contribute to gaining more knowledge about this growing patient population.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/terapia , Pneumonia em Organização Criptogênica/diagnóstico , Pneumonia em Organização Criptogênica/tratamento farmacológico , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Pneumonia em Organização Criptogênica/patologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Nasofaringe/virologia , Tomografia por Emissão de Pósitrons , Rituximab/uso terapêutico , SARS-CoV-2
7.
J Med Virol ; 94(1): 161-172, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415583

RESUMO

Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Evolução Molecular , SARS-CoV-2/genética , Monofosfato de Adenosina/uso terapêutico , Adolescente , Alanina/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Viral , Feminino , Haplótipos , Humanos , Lactente , Pulmão/virologia , Masculino , Filogenia , RNA Viral/análise , RNA Viral/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Carga Viral , Replicação Viral/efeitos dos fármacos
8.
J Med Virol ; 94(1): 197-204, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427922

RESUMO

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.


Assuntos
Vacinas contra COVID-19 , COVID-19/epidemiologia , SARS-CoV-2/genética , Ásia/epidemiologia , COVID-19/mortalidade , COVID-19/transmissão , COVID-19/virologia , Europa (Continente)/epidemiologia , Saúde Global , Humanos , Mutação , Índice de Gravidade de Doença , América do Sul/epidemiologia , Estados Unidos/epidemiologia
9.
J Med Virol ; 94(1): 222-228, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449894

RESUMO

The current study aimed at characterizing the dynamics of SARS-CoV-2 nucleocapsid (N) antigenemia in a cohort of critically ill adult COVID-19 patients and assessing its potential association with plasma levels of biomarkers of clinical severity and mortality. Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial plasma (n = 340) specimens were collected. A lateral flow immunochromatography assay and reverse-transcription polymerase chain reaction (RT-PCR) were used for SARS-CoV-2 N protein detection and RNA quantitation and in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were measured. SARS-CoV-RNA N-antigenemia and viral RNAemia were documented in 40.1% and 35.6% of patients, respectively at a median of 9 days since symptoms onset. The level of agreement between the qualitative results returned by the N-antigenemia assay and plasma RT-PCR was moderate (k = 0.57; p < 0.0001). A trend towards higher SARS-CoV-2 RNA loads was seen in plasma specimens testing positive for N-antigenemia assay than in those yielding negative results (p = 0.083). SARS-CoV-2 RNA load in tracheal aspirates was significantly higher (p < 0.001) in the presence of concomitant N-antigenemia than in its absence. Significantly higher serum levels of ferritin, lactose dehydrogenase, C-reactive protein, and D-dimer were quantified in paired plasma SARS-CoV-2 N-positive specimens than in those testing negative. Occurrence of SARS-CoV-2 N-antigenemia was not associated with increased mortality in univariate logistic regression analysis (odds ratio, 1.29; 95% confidence interval, 0.49-3.34; p = 0.59). In conclusion, SARS-CoV-2 N-antigenemia detection is relatively common in ICU patients and appears to associate with increased serum levels of inflammation and tissue-damage markers. Whether this virological parameter may behave as a biomarker of poor clinical outcome awaits further investigations.


Assuntos
COVID-19/virologia , Proteínas do Nucleocapsídeo de Coronavírus/sangue , Estado Terminal , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Biomarcadores/análise , Biomarcadores/sangue , COVID-19/mortalidade , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Fosfoproteínas/imunologia , Estudos Prospectivos , RNA Viral/análise , RNA Viral/sangue , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Traqueia/virologia , Adulto Jovem
10.
J Med Virol ; 94(1): 54-62, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427929

RESUMO

Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease period, there is an accumulating body of evidence concerning the late-onset complications of COVID-19, of which autoimmune manifestations have attracted remarkable attention from the first months of the pandemic. Autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. Clarification of the pathophysiology of COVID-19 injuries to the host, whether it is direct viral injury or autoimmunity, could help to develop appropriate treatment.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , COVID-19/patologia , SARS-CoV-2/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/virologia , COVID-19/imunologia , Humanos
11.
J Med Virol ; 94(1): 240-245, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460115

RESUMO

Many countries in the world are experiencing a recent surge in COVID-19 cases. This is mainly attributed to the emergence of new SARS-CoV-2 variants. Genome sequencing is the only means to detect the evolving virus mutants and emerging variants. Cycle threshold values have an inverse relationship with viral load and lower Ct values are also found to be associated with increased infectivity. In this study, we propose to use Ct values as an early indicator for upcoming COVID-19 waves. A retrospective cross-sectional study was carried out to analyze the Ct values of positive samples reported during the first wave and second wave (April 2020-May 2021). Median Ct values of confirmatory genes were taken into consideration for comparison. Ct values below 25, >25-30, and >30 were categorized as high, moderate, and low viral load respectively. Our study found a significantly higher proportion of positive samples with a low Ct value (<25) across age groups and gender during the second wave of the COVID-19 pandemic. A higher proportion of positive samples with a low Ct value (high viral load) may act as an early indicator of an upcoming surge.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Adolescente , Adulto , Infecções Assintomáticas/epidemiologia , COVID-19/virologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Carga Viral , Adulto Jovem
12.
Methods Mol Biol ; 2390: 103-112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34731465

RESUMO

The development of vaccines for the treatment of COVID-19 is paving the way for new hope. Despite this, the risk of the virus mutating into a vaccine-resistant variant still persists. As a result, the demand of efficacious drugs to treat COVID-19 is still pertinent. To this end, scientists continue to identify and repurpose marketed drugs for this new disease. Many of these drugs are currently undergoing clinical trials and, so far, only one has been officially approved by FDA. Drug repurposing is a much faster route to the clinic than standard drug development of novel molecules, nevertheless in a pandemic this process is still not fast enough to halt the spread of the virus. Artificial intelligence has already played a large part in hastening the drug discovery process, not only by facilitating the selection of potential drug candidates but also in monitoring the pandemic and enabling faster diagnosis of patients. In this chapter, we focus on the impact and challenges that artificial intelligence has demonstrated thus far with respect to drug repurposing of therapeutics for the treatment of COVID-19.


Assuntos
Antivirais/uso terapêutico , Inteligência Artificial , COVID-19/tratamento farmacológico , Descoberta de Drogas , Reposicionamento de Medicamentos , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/efeitos adversos , COVID-19/diagnóstico , COVID-19/virologia , Interações Hospedeiro-Patógeno , Humanos , Aprendizado de Máquina , Estrutura Molecular , SARS-CoV-2/patogenicidade , Relação Estrutura-Atividade
13.
Methods Mol Biol ; 2390: 177-190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34731469

RESUMO

We describe an approach to early stage drug discovery that explicitly engages with the complexities of human biology. The combined computational and experimental approach is formulated on a conceptual framework in which network biology is used to bridge between individual molecular entities and the cellular phenotype that emerges when those entities interact in a network. Multiple aspects of early stage discovery are addressed including the data-driven elucidation of biological processes implicated in disease, target identification and validation, phenotypic discovery of active molecules and their mechanism of action, and extraction of genetic target support from human population genetics data. Validation is described via summary of a number of discovery projects and details from a project aimed at COVID-19 disease.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Descoberta de Drogas , SARS-CoV-2/efeitos dos fármacos , Biologia de Sistemas , Animais , Antivirais/efeitos adversos , COVID-19/diagnóstico , COVID-19/virologia , Interações Hospedeiro-Patógeno , Humanos , Estrutura Molecular , Terapia de Alvo Molecular , SARS-CoV-2/patogenicidade , Relação Estrutura-Atividade
14.
Gene ; 806: 145935, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478821

RESUMO

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1-2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1-2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.


Assuntos
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Regiões 3' não Traduzidas , Adulto , Idoso , Antígeno B7-H1/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Predisposição Genética para Doença , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
15.
Life Sci Alliance ; 5(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34764206

RESUMO

Understanding pathways that might impact coronavirus disease 2019 (COVID-19) manifestations and disease outcomes is necessary for better disease management and for therapeutic development. Here, we analyzed alterations in sphingolipid (SL) levels upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection induced elevation of SL levels in both cells and sera of infected mice. A significant increase in glycosphingolipid levels was induced early post SARS-CoV-2 infection, which was essential for viral replication. This elevation could be reversed by treatment with glucosylceramide synthase inhibitors. Levels of sphinganine, sphingosine, GA1, and GM3 were significantly increased in both cells and the murine model upon SARS-CoV-2 infection. The potential involvement of SLs in COVID-19 pathology is discussed.


Assuntos
COVID-19/metabolismo , Modelos Animais de Doenças , Esfingolipídeos/metabolismo , Replicação Viral/fisiologia , Animais , COVID-19/prevenção & controle , COVID-19/virologia , Chlorocebus aethiops , Cromatografia Líquida/métodos , Dioxanos/farmacologia , Gangliosídeos/sangue , Gangliosídeos/metabolismo , Glucosiltransferases/antagonistas & inibidores , Glucosiltransferases/metabolismo , Humanos , Espectrometria de Massas/métodos , Camundongos Transgênicos , Pirrolidinas/farmacologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Esfingolipídeos/sangue , Esfingosina/análogos & derivados , Esfingosina/sangue , Esfingosina/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos
16.
Arch. pediatr. Urug ; 92(2): e212, dic. 2021. tab
Artigo em Espanhol | LILACS, BNUY, UY-BNMED | ID: biblio-1339132

RESUMO

Introducción: la sepsis tardía por estafilococo coagulasa negativo (SCoN) es una causa común de morbimortalidad en la unidad neonatal. Los SCoN son los microorganismos más frecuentemente involucrados con aproximadamente el 50% de los casos. El objetivo de este estudio es analizar la incidencia y las características de los neonatos portadores de sepsis tardía por SCoN. Materiales y métodos: se realizó un estudio descriptivo, longitudinal, retrospectivo. Se utilizaron las bases de datos del laboratorio de microbiología del hospital y las historias clínicas electrónicas para obtener la información. El período de estudio analizado fueron los años 2018 y 2019 en la unidad de cuidados intensivos e intermedios de recién nacidos del Centro Hospitalario Pereira Rossell. Resultados: obtuvimos una incidencia de 2,5% de los ingresos a cuidados intensivos e intermedios (25 pacientes). La edad gestacional al nacer fue de 28 semanas (25,0-35,0) y la mediana del peso fue de 1.070 g (730,0-2.365,0). La media de edad gestacional posmenstrual al momento del diagnóstico fue de 32,92±7,921 semanas. Por sospecha de sepsis precoz, 17 pacientes habían recibido un curso de antibióticos previo. El signo clínico más frecuentemente observado fue el deterioro del estado general, en 11 pacientes, seguido de distensión abdominal en 6 y fiebre en 5. Dentro de los SCoN, el más frecuentemente aislado fue el Staphylococcus epidermidis (13 pacientes); 22 pacientes recibieron tratamiento, 18 de ellos con vancomicina-meropenem y 4 con monoterapia con vancomicina. Conclusión: estos patógenos representan una causa importante de morbimortalidad en la unidad neonatal, particularmente en pacientes que presentan mayor gravedad y mayor necesidad de soporte vital. Se necesitan pautas claras de interpretación del rol de estos microorganismos y de abordaje de pacientes con riesgo de sepsis tardía, incluyendo el tratamiento antibiótico empírico.


Introduction: Coagulase Negative Staphylococci (CoNS) late onset sepsis is a common cause of morbidity and mortality in the neonatal intensive care unit (NICU). CoNS are the most frequently isolated microorganisms and total 50% of cases. The objective of this study is to analyze the incidence and characteristics of newborns carriers of late onset CoNS. Materials and methods: we performed a descriptive, retrospective, longitudinal study. Data was obtained from the hospital's microbiology laboratory database and electronic medical records. Patients included were those admitted to NICU during the period between 2018 and 2019. Results: we obtained an incidence of 2.5% of patients admitted to the NICU (25 patients). Median gestational age at birth was 28 weeks 25.0-35.0 and median birth weight was 1.070 g 730.0-2365.0. Mean gestational age at the time of diagnosis was 32.92±7.921 weeks. 17 patients had received an antibiotics course at birth because of early onset sepsis suspicion. The most frequently observed clinical symptom was deterioration of general condition, 11 patients, followed by abdominal distention in 6 and fever in 5. Among CoNS, the most frequently isolated pathogen was Staphylococcus epidermidis (13 patients). 22 patients received treatment, 18 a combination of vancomycin and meropenem and 4 received vancomycin monotherapy. Conclusion: these pathogens are a common cause of morbidity and mortality in the newborn intensive care unit, particularly in patients with more serious conditions and in those who require more advanced life support measures. Clearer interpretation of their role is needed as well as to determine a proper approach to patients at risk of late onset sepsis, including empiric antibiotic treatment.


Sepse tardia para Staphylococcus coagulase negativa (SCoN) é uma causa comum de morbidade e mortalidade na unidade neonatal. SCoNs são os microrganismos mais frequentemente envolvidos e representam aproximadamente 50% dos casos. O objetivo deste estudo é analisar a incidência e as características de neonatos com sepse tardia por SCoN. Materiais e métodos: foi realizado um estudo descritivo, longitudinal e retrospectivo. Usamos os bancos de dados do laboratório de microbiologia e prontuários médicos eletrônicos de nosso hospital para obter as informações. O período de estudo analisado foi de 2018 e 2019 na unidade de terapia intensiva e intermediária para recém-nascidos do Centro Hospitalar Pereira Rossell. Resultados: obtivemos uma incidência de 2,5% de internações em Terapia Intensiva e Intermediária (25 pacientes). A idade gestacional ao nascer foi de 28 semanas 25,0-35,0 e o peso médio foi de 1070g 730,0-2365,0. A média da idade gestacional pós-menstrual no momento do diagnóstico foi de 32,92 ± 7,921 semanas. 17 pacientes haviam recebido um curso anterior de antibióticos por suspeita de sepse precoce. O sinal clínico mais frequentemente observado foi deterioração do estado geral em 11 pacientes, seguido por distensão abdominal em 6 e febre em 5. Dentre os SCoN, o mais isolado foi o Staphylococcus Epidermidis (13 pacientes). 22 pacientes receberam tratamento, 18 deles com Vancomicina-Meropenem e 4 com Vancomicina em monoterapia. Conclusão: esses patógenos representam uma importante causa de morbimortalidade na unidade neonatal, principalmente em pacientes com maior gravidade e maior necessidade de suporte de vida. Orientações claras são necessárias para interpretar o papel desses microrganismos e para abordar pacientes com risco de sepse tardia, incluindo tratamento com antibióticos.


Assuntos
Humanos , Feminino , Recém-Nascido , Infecções Estafilocócicas/epidemiologia , Sepse Neonatal/epidemiologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/virologia , Uruguai/epidemiologia , Vancomicina/uso terapêutico , Infecção Hospitalar , Epidemiologia Descritiva , Incidência , Estudos Retrospectivos , Estudos Longitudinais , Coagulase , Staphylococcus haemolyticus/virologia , Staphylococcus hominis/virologia , Antibacterianos/uso terapêutico
17.
Front Immunol ; 12: 750229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745122

RESUMO

Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nasal turbinates was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.


Assuntos
Brônquios/patologia , COVID-19/complicações , COVID-19/imunologia , Furões/imunologia , SARS-CoV-2/fisiologia , Administração Intranasal , Fatores Etários , Animais , Doenças Assintomáticas , Modelos Animais de Doenças , Furões/virologia , Humanos , Hiperplasia , Imunidade Celular , Imunidade Humoral , Injeção Intratimpânica , Masculino , Internalização do Vírus
18.
Rev Med Virol ; 31(6): e2221, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34773448

RESUMO

The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.


Assuntos
Anti-Inflamatórios/uso terapêutico , Proteína C-Reativa/antagonistas & inibidores , COVID-19/tratamento farmacológico , Proteínas do Sistema Complemento/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , SARS-CoV-2/patogenicidade , Proteína ADAM17/antagonistas & inibidores , Proteína ADAM17/genética , Proteína ADAM17/imunologia , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Biomarcadores/sangue , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Celecoxib/uso terapêutico , Proteínas do Sistema Complemento/genética , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Progressão da Doença , Doxiciclina/uso terapêutico , Regulação da Expressão Gênica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Análise de Sobrevida
19.
Int J Mol Sci ; 22(21)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34769299

RESUMO

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.


Assuntos
Antivirais/farmacologia , Hidroxicolesteróis/química , Lipopeptídeos/química , SARS-CoV-2/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antivirais/química , Antivirais/uso terapêutico , Peso Corporal/efeitos dos fármacos , COVID-19/tratamento farmacológico , COVID-19/virologia , Coronavirus Humano 229E/efeitos dos fármacos , Coronavirus Humano 229E/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Coronavirus Humano OC43/efeitos dos fármacos , Coronavirus Humano OC43/patogenicidade , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Hidroxicolesteróis/farmacologia , Hidroxicolesteróis/uso terapêutico , Lipopeptídeos/farmacologia , Lipopeptídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Taxa de Sobrevida , Internalização do Vírus/efeitos dos fármacos
20.
Int J Mol Sci ; 22(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34769350

RESUMO

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin-angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.


Assuntos
COVID-19/patologia , Células Endoteliais/metabolismo , COVID-19/complicações , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Células Endoteliais/citologia , Células Endoteliais/virologia , Insuficiência Cardíaca/etiologia , Humanos , Insuficiência Renal/etiologia , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2/isolamento & purificação , Trombose/etiologia
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