Redox Homeostasis Alteration Is Restored through Melatonin Treatment in COVID-19 Patients: A Preliminary Study.

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.

Clinical and molecular characterization of children and adults with respiratory bocavirus infection in Mexico: a cross-sectional nested study within the ILI002 prospective observational study.

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.

Sociodemographic, clinical and laboratory characteristics and risk factors for mortality of hospitalized COVID-19 patients at alternate care site: a Latin American experience.

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.

N-Acetyl Cysteine Restores the Diminished Activity of the Antioxidant Enzymatic System Caused by SARS-CoV-2 Infection: Preliminary Findings.

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.

Etiology, clinical characteristics, and risk factors associated with severe influenza-like illnesses in Mexican adults.

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.

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study.

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.

Klebsiella pneumoniae K2 producer of pyogenic liver abscess associated with biliary communication.

INTRODUCTION: Hypervirulent strains of Klebsiella pneumoniae have gained clinical and epidemiological interest because of their capacity to cause severe and life-threatening infections. METHODOLOGY: We report a case involving infection with a hypervirulent K. pneumoniae K2 strain that caused liver abscess in a young woman with type 1 diabetes in Mexico. RESULTS: The infection was found to be associated with biliary tract communication. The virulence factors and capsular serotypes were identified by polymerase chain reaction analysis. After guided drainage and directed antibiotic treatment, the infection resolved and the patient recovered. Colonization of the gastrointestinal tract by hypervirulent K. pneumoniae strains, together with the presence of comorbidity, such as diabetes are important factors that contribute to the development of liver abscess. CONCLUSIONS: The identification of virulent clones is important to understand the pathogenicity and improve control of infections in the patients.

Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study.

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.

Different Clinical Presentations of Human Rhinovirus Species Infection in Children and Adults in Mexico.

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.

Analytical Performances of the COVISTIXTM Antigen Rapid Test for SARS-CoV-2 Detection in an Unselected Population (All-Comers).

The performance and validity of the COVISTIXTM rapid antigen test for the detection of SARS-CoV-2 were evaluated in an unselected population. Additionally, we assessed the influence of the Omicron SARS-CoV-2 variant in the performance of this antigen rapid test. Swab samples were collected at two point-of-care facilities in Mexico City from individuals that were probable COVID-19 cases, as they were either symptomatic or asymptomatic persons at risk of infection due to close contact with SARS-CoV-2 positive cases. Detection of the Omicron SARS-CoV-2 variant was performed in 91 positive cases by Illumina sequencing. Specificity and sensitivity of the COVISTIXTM rapid antigen test was 96% (CI 95% 94-98) and 81% (CI 95% 76-85), respectively. The accuracy parameters were not affected in samples collected after 7 days of symptom onset, and it was possible to detect almost 65% of samples with a Ct-value between 30 and 34. The COVISTIXTM antigen rapid test is highly sensitive (93%; CI 95% 88-98) and specific (98%; CI 95% 97-99) for detecting Omicron SARS-CoV-2 variant carriers. The COVISTIXTM rapid antigen test is adequate for examining asymptomatic and symptomatic individuals, including those who have passed the peak of viral shedding, as well as carriers of the highly prevalent Omicron SARS-CoV-2 variant.

Hyperglycemia and Loss of Redox Homeostasis in COVID-19 Patients.

The infection with SARS-CoV-2 impairs the glucose−insulin axis and this contributes to oxidative (OS) and nitrosative (NSS) stress. Here, we evaluated changes in glucose metabolism that could promote the loss of redox homeostasis in COVID-19 patients. This was comparative cohort and analytical study that compared COVID-19 patients and healthy subjects. The study population consisted of 61 COVID-19 patients with and without comorbidities and 25 healthy subjects (HS). In all subjects the plasma glucose, insulin, 8-isoprostane, Vitamin D, H2S and 3-nitrotyrosine were determined by ELISA. The nitrites (NO2−), lipid-peroxidation (LPO), total-antioxidant-capacity (TAC), thiols, glutathione (GSH) and selenium (Se) were determined by spectrophotometry. The glucose, insulin and HOMA-IR (p < 0.001), 8-isoprostanes, 3-nitrotyrosine (p < 0.001) and LPO were increased (p = 0.02) while Vitamin D (p = 0.01), H2S, thiols, TAC, GSH and Se (p < 0.001) decreased in COVID-19 patients in comparison to HS. The SARS-CoV-2 infection resulted in alterations in the glucose−insulin axis that led to hyperglycemia, hyperinsulinemia and IR in patients with and without comorbidities. These alterations increase OS and NSS reflected in increases or decreases in some oxidative markers in plasma with major impact or fatal consequences in patients that course with metabolic syndrome. Moreover, subjects without comorbidities could have long-term alterations in the redox homeostasis after infection.

Symptom cluster analysis of long COVID-19 in patients discharged from the Temporary COVID-19 Hospital in Mexico City.

INTRODUCTION: Several reports have emerged describing the long-term consequences of COVID-19 and its effects on multiple systems. METHODS: As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of the long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). RESULTS: We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p < 0.00001). Women were more prone than men to develop long-term symptoms, and invasive mechanical ventilation also increased the frequency of symptoms at 30 days post-discharge. CONCLUSION: Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.

Rapid establishment of a dedicated COVID-19 hospital in Mexico city during a public health crisis.

Healthcare systems worldwide have adapted and reorganized during the coronavirus disease 2019 (COVID-19) pandemic. Here, we provide a framework based on a public-private partnership that funded, developed, and operated a temporary COVID-19 hospital in Mexico City. We describe the creation of a collaborative network of primary healthcare triage centers and hospitals distributed throughout the city in recognition of demographic and geographic patterns that correlate with COVID-19 infections, including marginalized and impoverished areas of Mexico City. Additionally, we also report the hospital's cumulative outcomes over the 14 months of operation and show that it is feasible to transform a large public venue into a specialized hospital that incorporates a digital platform with robust clinical protocols to provide positive clinical outcomes.

During Mexico's response to the COVID-19 pandemic, the Carlos Slim Foundation (CSF), with a group of local foundations, academic institutions, and the Government of Mexico City, established a synergistic public­private partnership with the purpose of funding, designing, developing, and operating a dedicated COVID-19 hospital. This was achieved in 17 days by rapidly transforming into a hospital the largest convention center in Latin America, which is located in the heart of Mexico City. An ex professo network of eight dedicated respiratory triage community centers in coordination with other 40 federal and state primary health care clinics and hospitals was also established to streamline patient referral, thereby mitigating the impact of the COVID-19 pandemic in Mexico City's metropolitan area. We provide a framework for designing, funding, and executing the operations of a dedicated hospital in response to the COVID-19 pandemic that, from its conception, execution, operation, and closure, involved an exemplary coordination between public-private partnerships during a public health crisis. Referral, admission, treatment, clinical monitoring, discharge, and household follow-up were facilitated by the COVID360 digital health platform. The successful development and implementation of this multi-faceted digital platform allowed a lean patient-centered process, the management of clinical and administrative data, training of healthcare professionals, and the dissemination of accurate health information for data-driven decision making. This rapidly implemented temporary hospital dedicated to the comprehensive care of patients with COVID-19 was critical in coping with the increasing number of cases in Mexico City while achieving outstanding clinical outcomes.

Alteration in the Lipid Profile and the Desaturases Activity in Patients With Severe Pneumonia by SARS-CoV-2.

The kidnapping of the lipid metabolism of the host's cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host's own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.

"Differential risk of hospitalization among single virus infections causing influenza-like illnesses".

BACKGROUND: Acute respiratory infections are a major cause of morbidity in children and are often caused by viruses. However, the relative severity of illness associated with different viruses is unclear. The objective of this study was to evaluate the risk of hospitalization from different viruses in children presenting with an influenza-like illness (ILI). METHODS: Data from children 5 years old or younger participating in an ILI natural history study from April 2010 to March 2014 was analyzed. The adjusted odds ratio for hospitalization was estimated in children with infections caused by respiratory syncytial virus (RSV), metapneumovirus, bocavirus, parainfluenza viruses, rhinovirus/enterovirus, coronavirus, adenovirus, and influenza. RESULTS: A total of 1486 children (408 outpatients and 1078 inpatients) were included in this analysis. At least one virus was detected in 1227 (82.6%) patients. The most frequent viruses detected as single pathogens were RSV (n = 286), rhinovirus/enterovirus (n = 251), parainfluenza viruses (n = 104), and influenza A or B (n = 99). After controlling for potential confounders (age, sex, recruitment site, days from symptom onset to enrollment, and underlying illnesses), children with RSV and metapneumovirus infections showed a greater likelihood of hospitalization than those infected by parainfluenza viruses (OR 2.7 and 1.9, respectively), rhinovirus/enterovirus (OR 3.1 and 2.1, respectively), coronaviruses (OR 4.9 and 3.4, respectively), adenovirus (OR 4.6 and 3.2, respectively), and influenza (OR 6.3 and 4.4, respectively). CONCLUSIONS: Children presenting with ILI caused by RSV and metapneumovirus were at greatest risk for hospitalization, while children with rhinovirus/enterovirus, parainfluenza, coronavirus, adenovirus, and influenza were at lower risk of hospitalization.

Plasma cytokine levels and cytokine gene polymorphisms in Mexican patients during the influenza pandemic A(H1N1)pdm09.

BACKGROUND: In Mexico, the initial severe cases of the 2009 influenza pandemic virus A (H1N1) [A(H1N1)pdm09] were detected in early March. The immune mechanisms associated with the severe pneumonia caused by infection with this new virus have not been completely elucidated. Polymorphisms in interleukin genes have previously been associated with susceptibility to infectious diseases due to their influence on cytokine production. OBJECTIVES: The present case-control study was performed to compare several immunologic and genetic parameters of patients and controls during the initial phase of the pandemic. STUDY DESIGN: Sixty-five patients who were hospitalized due to infection with the influenza A(H1N1)pdm09 virus and 46 healthy controls were studied. A hemagglutination inhibition assay (HIA) was performed to measure anti-influenza antibody titers in these subjects. Protein levels of the cytokines interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), interferon gamma (IFNγ), transforming growth factor beta (TGFß)1 and TGFß2 were quantified in plasma. Single nucleotide polymorphisms in IL6, IL10 and TNFα were also assessed. RESULTS: Influenza patients had lower antibody titers and produced significantly higher levels of IL-6, IL-10 and TNFα than healthy controls. The frequencies of the TNFα -308G, IL-10 -592C and IL-10 -1082A alleles and the IL10 -1082(A/A) genotype were associated with susceptibility to severe disease, while the haplotypes TNFα AG and IL-10 GTA and GCA were associated with protection from severe disease [P=0.016, OR (CI)=0.11 (0.01-0.96); P=0.0187, OR (CI)=0.34 (0.13-0.85); P=0.013, OR (CI)=0.39 (0.18-0.83)]. CONCLUSIONS: This study demonstrates that the influenza A(H1N1)pdm09 patients and healthy controls have different profiles of immune parameters and that there is an association between IL-10 and TNFα polymorphisms and the outcome of this disease.

Diagnóstico y tratamiento de las infecciones en vías urinarias: un enfoque multidisciplinario para casos no complicados / Diagnosis and treatment of urinary tract infections: a multidisciplinary approach for uncomplicated cases

Las infecciones en vías urinarias afectan tanto a niños como a adultos. En niños son un problema de salud frecuente. En mujeres embarazadas merecen especial atención por los riesgos perinatales. La ausencia de nuevas moléculas antimicrobianas y el incremento en la resistencia bacteriana, favorecida por el uso indiscriminado de antibióticos, obliga a normar conductas para el abordaje y tratamiento inicial de las infecciones en vías urinarias. Este artículo fue desarrollado mediante un panel de médicos especialistas de instituciones de segundo y tercer nivel de atención, tanto públicas como privadas. Se realizó una revisión de la literatura. Ante la sospecha, el diagnóstico de infección en vías urinarias no complicada en niños debe confirmarse a través de medios bacteriológicos. El diagnóstico de infección en vías urinarias no complicada en adultos se realiza con base en el cuadro clínico. El tratamiento empírico inicial debe incluir la cobertura con antibióticos de amplio espectro y la adaptación del mismo de acuerdo con el resultado de los cultivos y de la sensibilidad reportada.

Urinary tract infection affects both children and adults. It is a common health problem in children. In pregnant women, treatment for urinary tract infection deserves special attention due to the perinatal risks. The absence of new antimicrobial molecules and the increase in bacterial resistance, the latter favored by the indiscriminate use of antibiotics, prompt us to standardize norms in the approach and initial treatment of urinary tract infection. The article was written by an independent panel from second- and third-level care public and private institutions. We conducted a review of the literature and the statements made within the framework of an interdisciplinary meeting. When urinary tract infection is suspected in children, diagnosis must be confirmed using bacteriological methods. Diagnosis of uncomplicated urinary tract infection in adults can be made based on the clinical examination. Empirical initial treatment must include wide-spectrum antibiotic options and should be modified according to culture results as well as reported sensitivity.

Difference between early clinical features of swine origin A H1N1 influenza confirmed and not confirmed infection in Mexico.

INTRODUCTION: The Swine Origin A H1N1 Influenza Virus (SOIV) pandemic emerged in April 2009 affecting people and health-care systems worldwide. This study examined the differences among the early clinical features presented in confirmed SOIV cases, those who tested negative for SOIV infection, fatalities, and hospitalized cases. METHODOLOGY: We reviewed 1,024 initial medical records of patients presenting with acute respiratory symptoms who attended the respiratory emergency room of a general hospital in Mexico and had a confirmatory test for influenza AH1N1 by RT-PCR from April to December 2009. RESULTS: Out of 1,024 cases, 457 (44%) were men with a mean age of 31±17 years; however, of these, SOIV confirmed cases were younger (26±8, p=0.000). SOIV infection was confirmed in 36% of the patients. Most (%?) cases presented mild infection, 20% of the patients required hospitalization, and 0.09% patients died. Asthma was more frequent in confirmed cases (p=0.028). Presence of COPD, systemic arterial hypertension, and diabetes mellitus was significant in confirmed hospitalized cases. Pulmonary rales, wheezing, and sudden symptom onset were more frequent and statistically significant in confirmed patients. Influenza-like illness was more frequent in confirmed cases (p=0.049).  CONCLUSIONS: This study presents one of the largest series of the new SOIV infection confirmed by RT-PCR reported. This infection is frequently mild and affects mainly young adults. Sudden symptoms onset, pulmonary rales, and wheezing are early features of this infection. Asthma, COPD, systemic arterial hypertension, and diabetes mellitus should be identified to identify potentially severe and fatal cases. ILI helps distinguish SOIV infection.

In vitro cytotoxicity of CD8+ T cells in multi-drug-resistant tuberculosis. A preliminary report.

BACKGROUND AND OBJECTIVE: Specific CD8+ T-cell cytotoxicity has been recognized as being involved in the elimination of drug-susceptible tuberculosis (DS-TB). Given that there is currently no information on the cytotoxic effector functions of CD8+ T cells in multi-drug-resistant tuberculosis (MDR-TB), our objective was to analyse the cytotoxic activity, both basal and stimulated, of CD8+ T cells from MDR-TB patients and compare it with that of DS-TB patients, as well as purified protein derivative (PPD)+ and PPD- subjects. METHODS: Cytotoxic activity of CD8+ T cells from MDR-TB patients, DS-TB patients, PPD+ and PPD- subjects was measured by a colorimetric assay, using H37Rv culture filtrate protein as the antigenic stimulus. RESULTS: Twenty-eight subjects were studied (7 MDR-TB patients, 7 DS-TB patients, 7 PPD+ subjects and 7 PPD- subjects). In the presence of the antigenic stimulus, the cytotoxic activity of CD8+ T cells from MDR-TB patients (% lysis) increased from 6.7% to 59.6% (P < 0.001). In DS-TB patients lysis increased from 3.2% to 22.5% (P < 0.001), whereas in PPD+ subjects it increased from 2.7% to 12.0% (P < 0.001) and in PPD- subjects from 1.3% to 3.2% (P < 0.001). Basal cytotoxic activity was significantly higher for MDR-TB patients than PPD+ and PPD- subjects (P = 0.003), but not compared with that for DS-TB patients (P = 0.05). Stimulated cytotoxic activity was highest for MDR-TB patients. CONCLUSIONS: CD8+ T cells from MDR-TB patients showed an exaggerated cytotoxic activity after antigenic stimulation. Further studies are required to elucidate the role of this response in the immunopathogenesis of MDR-TB.