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.

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.

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.

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.

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.

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.

Resultados de taatamiento de tuberculosis resisente en 91 pacientes del instittuto nacional de enfermedades respiratorias: 2001-2003

Introducción: La tuberculosis persiste como un problema mundial de salud pública. Aliviar la enfermedad, el sufrimiento y la muerte de los individuos causados por la tuberculosis es la principal inquietud humanitaria y requiere un enfoque de responsabilidad política social y económica centrado en el paciente para el control de esta enfermedad. Material y métodos: Se revisaron los expedientes de 91 pacientes con diagnóstico de tuberculosis farmacorresistente que fueron referidos al Instituto Nacional de Enfermedades Respiratorias por los servicios de salud de los distintos estados del país y del Distrito Federal. Los casos fueron clasificados al final, acorde con los criterios establecidos por la Organización Mundial de la Salud. Resultados: En el Grupo 1 el éxito fue del 63%, en el Grupo 2 del 100% y en el Grupo 3 del 41.8%. En el total de los tres grupos la tasa de éxito fue del 49%. Al hacer el análisis de estado por estado, los resultados menos favorables fueron Morelos con 0%, Puebla 25%, México 38%, y Distrito Federal 58% (7 de 12). Los mejores resultados obtenidos fueron en Veracruz con 77%, Guerrero con 75%, y Chiapas con 71%. Lo que hace evidente que la distancia no fue un factor de riesgo para el fracaso del tratamiento. Conclusiones: Los bajos resultados del estudio obligan a pensar que la prioridad es prevenir la aparición de casos multifarmacorresistentes al asegurar mejores tasas de curación, y reducir la diseminación de la enfermedad al tratar en forma eficiente a todos los casos nuevos.

Background: Tuberculosis (TB) persists as a public health world-wide problem. The principal human concern is to cure, relieve the suffering and reduce the mortality caused by this disease. A serious problem is the increasing prevalence of multidrug-resistant tuberculosis which contributes to the failure to erradicate TB. This requires an approach based on political, social and economic responsibility focused on the patient for TB control. Methods: We analyzed ninety-one files of patients with multidrug-resistant tuberculosis that were referred to the Institute by health services of different states and Mexico City. The cases were classified according to the criteria established by the World Health Organization (WHO). Results: In Group 1, the success rate was 63%, in Group 2 was 100% and in Group 3 was 41.8%. In the three groups the rate of success was 49%. After analyzing data by state, the worst results were from Morelos with 0%, Puebla 25%, Mexico state 38% and Mexico City with 58% (7 of 12). The best results were from Veracruz with 77%, Guerrero 75% and Chiapas 71%. This makes evident that the distance from the reference center is not a risk factor for treatment failure. Conclusions: It is imperative to prevent new cases of multidrug-resistant tuberculosis by increasing the rate of cure and to reduce the dissemination of the disease by efficiently treating all new cases.