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ABSTRACT Unvaccinated identical twins developed bilateral anterior uveitis soon after the onset of coronavirus disease 2019 symptoms. During follow-up, both patients developed choroiditis, and one twine developed posterior scleritis and serous retinal detachment. Prompt treatment with oral prednisone ameliorated the lesions, and no recurrence was observed at the 18-month follow-up. Choroiditis may rarely be associated with severe acute respiratory syndrome coronavirus 2 infection, and it responds well to corticosteroid therapy. Although the exact mechanism is unknown, we hypothesize that the virus may act as an immunological trigger for choroiditis.
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Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses regarding SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear B-cell epitopes in its spike glycoprotein with an SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. The bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), which was confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA for anti-SARS-CoV-2 antibodies. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infections of monocytes was observed in vitro with pre-pandemic Dengue-positive sera. A significant increase in viral load was measured compared to that of the controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. Cross-reactivity against peptides from spike proteins was observed for the pre-pandemic sera. This study highlights the importance of identifying specific epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future infections on diseases and their impact on vaccinations and immunodiagnostics.
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Anticorpos Antivirais , COVID-19 , Reações Cruzadas , Vírus da Dengue , Epitopos de Linfócito B , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Glicoproteína da Espícula de Coronavírus/imunologia , Humanos , Reações Cruzadas/imunologia , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/virologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Epitopos de Linfócito B/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Dengue/virologia , Anticorpos Facilitadores/imunologia , Pandemias , Epitopos Imunodominantes/imunologiaRESUMO
OBJECTIVE: This study aimed to evaluate the Neuropsychomotor Development (NPMD) of newborns exposed to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age. METHODS: Childcare appointments were scheduled for the included newborns in the study. During the 6-month consultation, the Screening Test for Bayley III Scale and, based on it, children were classified as "low risk", "moderate risk" or "high risk" in the domains: of cognitive, receptive language, expressive language, fine motor, and gross motor. Those classified as "moderate risk"; or "high risk" received guidance about NPMD stimuli and were instructed to maintain follow-up. RESULTS: Only 13 (37.1 %) of the newborns were classified as low risk in receptive language and 18 (51.4 %) in gross motor skills, with the domains most affected. Prematurity was a risk for cognitive incompetence (moderate risk/high-risk classification) (coefficient: 1.89, Odds Ratio = 6.7, 95 % CI 1.3â35, p = 0.02). Lower birth weight that 2.500g had a similar effect on cognitive incompetence (coefficient: 1.9, Odds Ratio = 6.2, 95 % CI 1.2â32.2, p = 0.02). Exclusive breastfeeding at hospital discharge (n = 8) was protective for incompetence (high risk/moderate risk) in the language domain (coefficient -2.14, OR = 0.12, 95 % CI 0.02â0.71, p = 0.02). CONCLUSIONS: The children included in the study must be monitored and their development monitored in order to clarify whether there is a relationship between the delay in NPMD and perinatal exposure to COVID-19, as delays were observed in these preliminary results.
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COVID-19 , Desenvolvimento Infantil , Testes Neuropsicológicos , SARS-CoV-2 , Humanos , Feminino , Recém-Nascido , Masculino , Desenvolvimento Infantil/fisiologia , Lactente , Gravidez , Destreza Motora/fisiologia , Deficiências do Desenvolvimento/etiologia , Fatores de RiscoRESUMO
The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.
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COVID-19 , Pré-Eclâmpsia , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , COVID-19/fisiopatologia , COVID-19/imunologia , Gravidez , Feminino , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/imunologia , SARS-CoV-2/fisiologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Sistema Renina-AngiotensinaRESUMO
Background: COVID-19 is still a global health issue, there is limited evidence in South America regarding laboratory biomarkers associated with severe disease. The objective of our study was to identify hematological and hemostatic changes associated with severe COVID-19. Methods: A total of 170 hospitalized patients with COVID19 were included in the study, defining their severity according to established criteria. Demographic, clinical, and laboratory (days 1, 3, 7, 15) data were obtained. We performed a statistical analysis, assuming significance with a value of p < 0.05. We analyzed the correlation between severity and biomarkers and established cut-off values for severe patients through ROC curves, estimating Odds Ratio associated with severe disease. Results: Day 1 was observed significant differences between moderate vs severe patients for leukocytes (WBC), Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and D-dimer, establishing cut-off points for each of them. The markers we found associated to risk of severe disease were WBC (OR=3.2396; p = 0.0003), NLR (OR=5.7084; p < 0.0001), PLR (OR=4.4094; p < 0.0001), Neutrophil (OR=4.1193; p < 0.0001), D-dimer (OR=2.7827; p = 0.0124). Conclusions: The results allow to establish basic laboratory biomarkers associated to severe disease, which could be used as prognostic markers.
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Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.
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Anosmia , Encéfalo , COVID-19 , Imageamento por Ressonância Magnética , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/psicologia , COVID-19/fisiopatologia , COVID-19/diagnóstico por imagem , COVID-19/patologia , Anosmia/etiologia , Anosmia/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , SARS-CoV-2/isolamento & purificação , Idoso , Tomada de Decisões , Cognição/fisiologiaRESUMO
Lipid droplets (LD) are crucial for maintaining lipid and energy homeostasis within cells. LDs are highly dynamic organelles that present a phospholipid monolayer rich in neutral lipids. Additionally, LDs are associated with structural and non-structural proteins, rapidly mobilizing lipids for various biological processes. Lipids play a pivotal role during viral infection, participating during viral membrane fusion, viral replication, and assembly, endocytosis, and exocytosis. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection often induces LD accumulation, which is used as a source of energy for the replicative process. These findings suggest that LDs are a hallmark of viral infection, including SARS-CoV-2 infection. Moreover, LD participates in the inflammatory process and cell signaling, activating pathways related to innate immunity and cell death. Accumulating evidence demonstrates that LD induction by SARS-CoV-2 is a highly coordinated process, aiding replication and evading the immune system, and may contribute to the different cell death process observed in various studies. Nevertheless, recent research in the field of LDs suggests these organelles according to the pathogen and infection conditions may also play roles in immune and inflammatory responses, protecting the host against viral infection. Understanding how SARS-CoV-2 influences LD biogenesis is crucial for developing novel drugs or repurposing existing ones. By targeting host lipid metabolic pathways exploited by the virus, it is possible to impact viral replication and inflammatory responses. This review seeks to discuss and analyze the role of LDs during SARS-CoV-2 infection, specifically emphasizing their involvement in viral replication and the inflammatory response.
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The present work reports the inhibitory effect of amides derived from gallic acid (gallamides) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), along with cytotoxicity evaluation and molecular docking studies. In addition to gallamides, other relevant compounds were also synthesized and evaluated against Mpro, making a total of 25 compounds. Eight compounds presented solubility issues during the inhibitory assay and one showed no inhibitory activity. Compounds 3a, 3b, and 3f showed the highest enzymatic inhibition with IC50 = 0.26 ± 0.19 µM, 0.80 ± 0.38 µM, and 2.87 ± 1.17 µM, respectively. Selenogallamide 6a exhibited IC50 values of 5.42 ± 2.89 µM and a comparison with its nonselenylated congener 3c shows that the insertion of the chalcogen moiety improved the inhibitory capacity of the compound by approximately 10 times. Regarding the cellular toxicity in THP-1 and Vero cells, compounds 3e and 3g, showed moderate cytotoxicity in Vero cells, while for THP-1 both were nontoxic, with CC50 > 150 µM. Derivative 3d showed moderate cytotoxicity against both cell lines, whereas 6d was moderatly toxic to THP-1. Other compounds analyzed do not induce substantial cellular toxicity at the concentrations tested. The molecular docking results for compounds 3a, 3b, and 3f show that hydrogen bonding interactions involving the hydroxyl groups (OH) of the gallate moiety are relevant, as well as the carbonyl group.
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Introduction: This report aimed to analyze the outcomes of patients with obesity who were on a bariatric program during the SARS-Cov-2 pandemic outbreak and compare those who received surgery with the ones who were not operated on. Methods: This was a retrospective study between 2020 and 2021. Patients were divided into two groups: those who underwent surgery (O) and those who were not operated (NO). The evolution of the risk factors identified for severe COVID infection and death was studied (ASMBS criteria). For this study, a follow-up period of 12 months was initiated. Results: In the O group, 83 patients were included and 99 were in the NO group. In the O group, patients with body mass index (BMI) > 35 Kg/m2 before surgery resolved the condition in 73.5% (61) cases, and this was done in the first 30 days by 38 (45.7%). Type 2 diabetes mellitus remission was documented in 18 patients (85.7%) of the O group, and the mean time elapsed for remission was 102.2 days (P < .01). Hypertension remitted in 66.7% (20) of the patients in group O in 82.4 days (P < .01). The subgroup of patients with obesity and one high-risk associated condition (30.2%, 25) resolved both in 44% (11) cases and one in 48% (12) cases. In the group of patients with obesity and two high-risk associated conditions (15.6%, 13), 47% (6) patients resolved the three conditions, 38% (5) resolved two conditions, and 15% (2) resolved one condition. Among the NO group, no comorbidity resolutions were recorded (P < .01). Admission because of COVID infection was necessary for 7.1% of NO and 1.2% of O (P = .04). Conclusion: Bariatric metabolic surgery would not increase the risk of COVID infection or of suffering serious complications resulting from it. Patients undergoing bariatric metabolic surgery rapidly resolved high-risk comorbidities and had less need for hospitalization because of SARS-CoV-2 infection.