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SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process.

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Objectives: Influenza-like illness (ILI) caused by respiratory viruses results in various respiratory clinical manifestations. The ILI002 prospective observational cohort study aimed to describe viral agents, seasonality, and outcomes of patients with ILI during four seasons in the influenza H1N1-pandemic and post-pandemic years (2010-2014). Methods: Patients from six Mexican hospitals were enrolled from April 2010 to March 2014. Clinical data and nasopharyngeal swabs were obtained and tested for viral respiratory pathogens by real-time reverse-transcription polymerase chain reaction. Results: Of the 5662 enrolled participants, 64.9% were adults and 35.1% were children. Among the 5629 participants with single-pathogen detection, rhinovirus (20.2%), influenza virus (11.2%), respiratory syncytial virus (RSV) (7.2%), and coronavirus (6.8%) were the most frequent pathogens. Co-infection occurred in 14.5% of cases; 49.3% of participants required hospitalization, particularly in RSV cases (42.9% adults, 89.6% children). The mortality rate was 2.8% higher among older adult participants and those with comorbidities. Influenza H1N1 had the highest mortality rate, yet almost half of the deceased had no pathogen. Rhinovirus persisted year-round, while influenza, coronavirus, and RSV peaked during cooler months. Conclusions: Analyses showed that some viruses causing ILI may lead to severe disease and hospitalization irrespective of comorbidities. These findings may help in decision-making about public health policies on prevention measures, vaccination, treatment, and administration of health care.

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Type II pneumocytes are the target of the SARS-CoV-2 virus, which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. In this study, we evaluated whether treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), lipid peroxidation (LPO), and thiol groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There were significant increases in LPO and carbonyl quantities (p ≤ 0.03) and decreases in TAC and the quantities of NO2-, thiols, and GSH (p < 0.001) in COVID-19 patients. The activities of the antioxidant enzymes such as ecSOD, TrxR, GPx, GST, GR, and peroxidases were decreased (p ≤ 0.04) after the MT treatment. The treatment with MT favored the activity of the antioxidant enzymes that contributed to an increase in TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis, functioning as a glycolytic agent, and inhibited the Warburg effect. Thus, MT restores the redox homeostasis that is altered in COVID-19 patients and can be used as adjuvant therapy in SARS-CoV-2 infection.

Assuntos

Antioxidantes , Tratamento Farmacológico da COVID-19 , COVID-19 , Homeostase , Melatonina , Oxirredução , Estresse Oxidativo , SARS-CoV-2 , Melatonina/uso terapêutico , Melatonina/farmacologia , Humanos , Oxirredução/efeitos dos fármacos , COVID-19/metabolismo , COVID-19/virologia , COVID-19/sangue , Homeostase/efeitos dos fármacos , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Idoso , Adulto , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo , Glutationa/sangue

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Background: Human Bocaviruses (HBoV) can cause acute respiratory tract infections. High coinfection rates cloud its pathogenicity. This study sought to describe the clinical features of HBoV1 disease in children and adults with Influenza-like illness (ILI), exploring associations between viral load, clinical features, and seasonality. Methods: Patients who tested positive for HBoV1 by polymerase chain reaction, enrolled from April 2010 to March 2014 in the ILI002 prospective observational cohort study were included in this cross-sectional nested study. Participants were included in ILI002 if they presented with signs and/or symptoms suggestive of influenza-like illness. Samples were tested for viral load, and NP1 and VP1/VP2 phylogenetic analyses, except for the samples lacking suitable and viable clinical material for genotyping. Findings: We identified HBoV1 in 157 (2.8%) of participants. Prevalence was 4.5% in children and 1.8% in adults. Single HBoV1 detection occurred in 41.1% and 46.3% of children and adults, respectively. Children commonly experienced fever (83.3%), cough with sputum (74.4%), and shortness of breath (72.2%). In the multivariate analysis of children, significant positive associations were detected between viral loads and age (0.20 [95% CI: 0.07, 0.33]), and the presence of fever (2.64 [95% CI: 1.35, 3.94]), nasal congestion (1.03 [95% CI: 0.07, 1.99]), dry cough (1.32 [95% CI: 0.42, 2.22]), chest congestion (1.57 [95% CI: 0.33, 2.80]), red eyes (1.25 [95% CI: 0.35, 2.14]), cough with sputum (1.79 [95% CI: 0.80, 2.78]), and other signs and symptoms such as chills, dizziness, and diaphoresis (1.73 [95% CI: 0.19, 3.27]). In contrast, significant negative associations were found between viral loads and percent neutrophils on the blood count (-0.04 [95% CI: -0.06, -0.02]), fatigue (-1.60 [95% CI: -2.46, -0.74]) and the presence of other symptoms or signs, including adenopathy and rash (-1.26 [95% CI: -2.31, -0.21]). Adults commonly experienced sore throat (73.1%), fatigue (77.4%), and headache (73.1%). In the multivariate analysis of adults, significant positive associations were detected between viral load and body mass index (0.13 [95% CI: 0.04, 0.21]), and the presence of confusion (1.54 [95% CI: 0.55, 2.53]), and sore throat (1.03 [95% CI: 0.20, 1.85]), and significant negative associations were detected between viral load and chest congestion (-1.16 [95% CI: -2.07, -0.24]). HBoV1 was detected throughout the year irrespective of season, temperature, and humidity. Interpretation: This study demonstrated the importance of detecting HBoV1 in patients with influenza-like illness either as single infection or co-infection, in both adults and children, and improves the characterization of HBoV1 seasonality, clinical features, and viral load. Phylogenetic analyses show a high conservation. Funding: The Mexican Emerging Infectious Diseases Clinical Research Network (LaRed), CONACYT (Fondo Sectorial SSA/IMSS/ISSSTE, Projects No. 71260 and No. 127088), Fondos federales no. HIM/2015/006, NIAID, NIH through a contract with Westat, Inc. (HHSN2722009000031, HHSN27200002), NCI, NIH (75N91019D00024, 75N91019F00130). Additional information at the end of the manuscript.

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BACKGROUND: The establishment of Alternate Care Sites (ACS) helped the most severely impacted countries expand their response capability. The aim of this study was to evaluate the clinical characteristics and risk factors associated with the mortality of hospitalized COVID-19 patients at Alternate Care Site in Mexico City. PATIENTS AND METHODS: A monocentric cohort study was conducted at Mexico City's Temporary Unit COVID-19 (UTC-19). Sociodemographic, clinical, laboratory and treatment variables were included in the analysis. RESULTS: A total of 4865 patients were included, with a mean age of 49.33 years ± SD 15.28 years (IQR 38 to 60 years); 50.53% were women. 63.53% of the patients presented at least one comorbidity, the most frequent being: obesity (39.94%), systemic arterial hypertension (25.14%), and diabetes mellitus (21.52%). A total of 4549 patients (93.50%) were discharged due to improvement, 64 patients (1.31%) requested voluntary discharge, 39 patients (0.80%) were referred to another unit, and 213 patients (4.37%) died. Factors that were independently and significantly associated with death included male gender (odds ratio [OR], 1.60), age ≥ 50 years (OR 14.75), null or low schooling (OR 3.47), have at least one comorbidity (OR 3.26), atrial fibrillation (OR 22.14). In the multivariate analysis, the lymphopenia ≤ 1 × 103/µL (OR 1.91), and having required steroid treatment (OR 2.85), supplemental oxygen with high-flow nasal cannula (OR 3.12) or invasive mechanical ventilation (OR 42.52), was significantly associated with an increased risk of death. CONCLUSIONS: This study identified the clinical characteristics and risk factors for mortality of hospitalized COVID-19 patients at ACS in Mexico City.KEY MESSAGESAn Alternate Care Site (ACS) is any building or structure that is temporarily converted or constructed for healthcare use during a public health emergency.Factors associated with death included male gender, age over 50 years, and lower educational attainment (elementary school or less).The findings corroborate the utility of the CALL score as a predictor of mortality; lymphopenia ≤1 × 103/µL was the most relevant biomarker.

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COVID-19 , Linfopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/terapia , SARS-CoV-2 , América Latina , Estudos de Coortes , Fatores de Risco

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SARS-CoV-2 infects type II pneumocytes and disrupts redox homeostasis by overproducing reactive oxygen species (ROS). N-acetyl cysteine (NAC) is a precursor of the synthesis of glutathione (GSH) and it restores the loss of redox homeostasis associated to viral infections. The aim of the study is to evaluate the effect of the treatment with NAC on the enzymatic antioxidant system in serum from patients infected by SARS-CoV-2. We evaluated the enzymatic activities of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), -S-transferase (GST), and reductase (GR) by spectrophotometry and the concentrations of the glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), and lipid peroxidation (LPO) in serum. The activity of the extracellular super oxide dismutase (ecSOD) was determined by native polyacrylamide gels, and 3-nitrotyrosine (3-NT) was measured by ELISA. A decrease in the activities of the ecSOD, TrxR, GPx, GST GR, (p = 0 ≤ 0.1), and the GSH, TAC, thiols, and NO2- (p ≤ 0.001) concentrations and an increase in LPO and 3-NT (p = 0.001) concentrations were found in COVID-19 patients vs. healthy subjects. The treatment with NAC as an adjuvant therapy may contribute to a reduction in the OS associated to the infection by SARS-CoV-2 through the generation of GSH. GSH promotes the metabolic pathways that depend on it, thus contributing to an increase in TAC and to restore redox homeostasis.

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Objective: The aim of this study was to determine the risk factors associated with severe influenza-like illness (ILI) in Mexican adults that could be useful to clinicians when assessing patients with ILI. Methods: Data from adult patients enrolled from 2010 through 2014 in ILI002 - a prospective hospital-based observational cohort study - were analyzed. Etiology and clinical characteristics were compared between cases of severe ILI (defined as hospitalization and/or death) and cases of non-severe ILI. Results: Overall, 1428 (39.0%) out of a total 3664 cases of ILI were classified as severe. Adjusted analyses showed a higher risk of severe ILI associated with signs and symptoms related to lower tract infection, i.e. cough with sputum (odds ratio (OR) 2.037, 95% confidence interval (CI) 1.206-3.477; P = 0.008), dyspnea (OR 5.044, 95% CI 2.99-8.631; and shortness of breath (OR 5.24, 95% CI 3.0839.124; P < 0.001), and with increases in lactate dehydrogenase (OR 4.426, 95% CI 2.321-8.881; P < 0.001) and C-reactive protein (OR 3.618, 95% CI 2.5955.196; P < 0.001). Further, there was an increased risk of severe ILI with a longer time between symptom onset and inclusion (OR 1.108, 95% CI 1.049-1.172; P < 0.001) and with chronic steroid use (OR 14.324, 95% CI 8.059-26.216; P < 0.001). Conclusions: Respiratory viruses can cause severe ILI. The results of this study highlight the importance of evaluating data compatible with lower tract involvement and previous use of immunosuppressants at baseline, because patients meeting these conditions may develop severe illness.

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BACKGROUND: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. METHODS: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. RESULTS: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1ß (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. CONCLUSION: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Assuntos

COVID-19 , Humanos , COVID-19/complicações , Projetos Piloto , Síndrome de COVID-19 Pós-Aguda , Linfócitos T CD8-Positivos , Estudos de Coortes , Quimiocina CXCL10 , Obesidade

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Background: Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods: We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results: At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion: A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.

Assuntos

COVID-19 , Anticorpos Antivirais , Linfócitos T CD8-Positivos , Quimiocinas , Estudos de Coortes , Estado Terminal , Citocinas , Humanos , Imunoglobulina G , SARS-CoV-2

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Background: Human rhinoviruses (HRVs) are a common cause of influenza-like illness, with the ability to infect the upper and lower respiratory tracts. In this study we aim to describe the clinical and molecular features of HRV infection in Mexican children and adults. Methods: We performed a hospital-based, 4-year multicenter prospective observational cohort study of patients with influenza-like illness. Participants who tested positive for HRV were included. We described demographic, clinical, and laboratory characteristics and the association between HRV types, illness severity, and clinical outcomes. Results: Of the 5662 subjects recruited, 1473 (26%) had HRV; of those, 988 (67.1%) were adults (≥18 years) and 485 (32.9%) were children. One hundred sixty-seven (11.33%) samples were sequenced; 101 (60.5%) were rhinovirus species A (HRV-A), 22 (13.2%) were rhinovirus species B (HRV-B), and 44 (26.3%) were rhinovirus species C (HRV-C). Among children and adults, 30.5% and 23.5%, respectively, were hospitalized (non-intensive care unit [ICU]). The odds of HRV-C are higher than HRV-A for participants in the ICU (compared to outpatient) and when platelets, lymphocytes, white blood cells, and lactate dehydrogenase are increased. The odds of HRV-C are higher than HRV-A and HRV-B with shortness of breath. The odds of HRV-A are higher than HRV-B, and the odds of HRV-B are higher than HRV-C, when mild symptoms like muscle ache and headache occur. Conclusions: Rhinoviruses are a common cause of influenza-like illness. It is necessary to improve the surveillance, testing, and species identification for these viruses to understand different clinical presentations and risk factors associated with worse outcomes. Clinical Trials Registration. NCT01418287.