Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

Viral Biology and Immune Privilege in the Development of Extrahepatic Manifestations During Hepatitis E Virus Infection.

Hepatitis E virus (HEV) exhibits tropism toward hepatocytes and thus affects the liver; however, HEV may also affect other tissues, including the heart, kidneys, intestines, testicles, and central nervous system. To date, the pathophysiological links between HEV infection and extrahepatic manifestations have not yet been established. Considering that HEV infects multiple types of cells, the direct effects of virus replication in peripheral tissues represent a plausible explanation for extrahepatic manifestations. In addition, since the immune response is crucial in the development of the disease, the immune characteristics of affected tissues should be revisited to identify commonalities explaining the effects of the virus. This review summarizes the most recent advances in understanding the virus biology and immune-privileged status of specific tissues as major elements for HEV replication in diverse organs. These discoveries may open avenues to explain the multiple extrahepatic manifestations associated with HEV infection and ultimately to design effective strategies for infection control.

Cryptococcal Meningitis in a Mexican Neurological Center.

BACKGROUND: Cryptococcal meningitis, one of the most severe infections affecting the central nervous system, often involves severe neurological sequels and high mortality. METHODS: A retrospective review was performed, including 76 cases admitted in a 10-year period at a neurological referral center in Mexico City. From 68 isolates, 52 fungal specimens were identified as part of the Cryptococcus neoformans var. neoformans complex, 15 as C. neoformans var gattii complex, and one as Cryptococcus non- neoformans/gattii . RESULTS: Higher cryptococcal meningitis incidence and severity were found in HIV-infected men; other risk factors frequently observed were diabetes mellitus and labor exposure to poultry. The main clinical manifestations were subacute headache, cognitive alterations, and photophobia (exclusively in HIV patients). MRI was highly sensitive for pathologic findings such as meningeal enhancements and cryptococcomas, most of them associated to C. neoformans complex. Eleven patients developed severe brain vasculitis, as observed by transcranial Doppler. Hydrocephalus with intracranial hypertension was the most frequent complication. CONCLUSIONS: One-half of the population died, and the rest had neurological sequels, mainly neuropsychiatric manifestations and secondary headaches. These patients developed severe functional limitations in performing daily activities in an independent manner.

Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

An RBD-Based Diagnostic Method Useful for the Surveillance of Protective Immunity against SARS-CoV-2 in the Population.

After more than two years, the COVID-19 pandemic is still ongoing and evolving all over the world; human herd immunity against SARS-CoV-2 increases either by infection or by unprecedented mass vaccination. A substantial change in population immunity is expected to contribute to the control of transmission. It is essential to monitor the extension and duration of the population's immunity to support the decisions of health authorities in each region and country, directed to chart the progressive return to normality. For this purpose, the availability of simple and cheap methods to monitor the levels of relevant antibodies in the population is a widespread necessity. Here, we describe the development of an RBD-based ELISA for the detection of specific antibodies in large numbers of samples. The recombinant expression of an RBD-poly-His fragment was carried out using either bacterial or eukaryotic cells in in vitro culture. After affinity chromatography purification, the performance of both recombinant products was compared by ELISA in similar trials. Our results showed that eukaryotic RBD increased the sensitivity of the assay. Interestingly, our results also support a correlation of the eukaryotic RBD-based ELISA with other assays aimed to test for neutralizing antibodies, which suggests that it provides an indication of protective immunity against SARS-CoV-2.

Asociación entre dependencia funcional y calidad de vida en pacientes adultos mayores oncológicos / Association between functional dependence and quality of life in older adult oncology patients

RESUMEN Introducción: La presencia de comorbilidades modula el proceso de envejecimiento, el diagnóstico de cáncer puede comprometer de manera importante la salud del adulto mayor, lo cual repercute en su calidad de vida. Objetivo: Determinar la asociación entre la dependencia funcional y la calidad de vida en pacientes oncológicos adultos mayores tratados con radioterapia. Métodos: Estudio analítico retrospectivo, realizado en 181 pacientes ambulatorios del Centro Médico Naval del Callao, Perú, varones, mayores de 60 años. Se valoró la dependencia funcional mediante los índices de Barthel y el de Lawton; y la calidad de vida mediante la escala de calidad de vida en adultos mayores de la Organización Mundial de la Salud (WHOQoL-Old). Resultados: Se encontró asociación estadísticamente significativa entre dependencia funcional y calidad de vida, tanto para las actividades básicas de la vida diaria (PR= 1,04 [IC 95 %; 1,01-1,07]) como para las actividades instrumentales de la vida diaria (PR= 1,08 (IC 95 %: 1,01 - 1,13). Conclusiones: En los pacientes adultos mayores oncológicos tratados con radioterapia, se encuentra asociación significativa entre dependencia funcional y una pobre calidad de vida.

ABSTRACT Introduction: The presence of comorbidities modulates the aging process, the diagnosis of cancer can significantly compromise the health of the elderly, which affects their quality of life. Objective: Determine the association between the functional dependence and the quality of life in elderly oncology patients treated with radiotherapy. Methods: Retrospective analytical study, carried out in 181 outpatients of Centro Médico Naval del Callao, Perú, male, older than 60 years. The functional dependence was assessed with Barthel index and Lawton scale; and the quality of life was assessed with World Health Organization Quality of Life-Older Adults Module (WHOQoL-Old). Results: A statistically significant association was found between functional dependence and quality of life, for both the basic activities of daily living (PR= 1.04 [IC 95 %: 1.01-1.07]), and the instrumental activities of daily living (PR= 1.08 [IC 95 %: 1.01 - 1.13]). Conclusion: There was significant association between the functional dependence and the poor quality of life in the elderly oncology patients treated with radiotherapy.

Gut dysbiosis and homocysteine: a couple for boosting neurotoxicity in Huntington disease.

Huntington's disease (HD), a neurodegenerative disorder caused by an expansion of the huntingtin triplet (Htt), is clinically characterized by cognitive and neuropsychiatric alterations. Although these alterations appear to be related to mutant Htt (mHtt)-induced neurotoxicity, several other factors are involved. The gut microbiota is a known modulator of brain-gut communication and when altered (dysbiosis), several complaints can be developed including gastrointestinal dysfunction which may have a negative impact on cognition, behavior, and other mental functions in HD through several mechanisms, including increased levels of lipopolysaccharide, proinflammatory cytokines and immune cell response, as well as alterations in Ca2+ signaling, resulting in both increased intestinal and blood-brain barrier (BBB) permeability. Recently, the presence of dysbiosis has been described in both transgenic mouse models and HD patients. A bidirectional influence between host brain tissues and the gut microbiota has been observed. On the one hand, the host diet influences the composition and function of microbiota; and on the other hand, microbiota products can affect BBB permeability, synaptogenesis, and the regulation of neurotransmitters and neurotrophic factors, which has a direct effect on host metabolism and brain function. This review summarizes the available evidence on the pathogenic synergism of dysbiosis and homocysteine, and their role in the transgression of BBB integrity and their potential neurotoxicity of HD.

Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients.

BACKGROUND: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. METHODS: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. CONCLUSIONS: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.

Neuroinflammation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection: Pathogenesis and clinical manifestations.

Peripheral inflammation and neuroinflammation are host-mounted to eliminate injury, infection, or toxin to restore homeostasis. However, when inflammation persists, it may promote collateral tissue damage that ultimately culminates in pathological peripheral damage or neurodegeneration. Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, responsible of Coronavirus disease 2019 (COVID-19), accumulating evidence describes neurological manifestations and complications worldwide particularly in approximately one-third of patients with COVID-19 particularly in those affected with the severe forms of the disease. Different access routes to the central nervous system have been identified. One immediately used is the entrance by the olfactory and trigeminus nervous affecting olfactory and sensory nerve endings when individuals get the infection by the intranasal route. It can also reach the central nervous system through the choroid plexuses and periventricular areas that lack blood-brain barrier or by its disruption by the exacerbated peripheral inflammation. Until now, the long-term sequelae of SARS-CoV-2 infection is still under research and the post-COVID syndrome. This review focuses on the consequences of the neuroinflammatory response in patients with COVID-19 considering its potential relevance in the appearance of neurological sequelae including neurodegenerative disorders.

Pharmacokinetic Study of Intranasal Dexamethasone and Methylprednisolone Compared with Intravenous Administration: Two Open-Label, Single-Dose, Two-Period, Two-Sequence, Cross-Over Study in Healthy Volunteers.

Dexamethasone (DXM) and methylprednisolone (MEP) are potent glucocorticoids used to control several inflammatory conditions. Evidence of delayed DXM reaching the central nervous system (CNS) as well as tachyphylaxis and systemic, undesirable side effects are the main limitations of peripheral delivery. Intranasal administration offers direct access to the brain as it bypasses the blood-brain barrier. The Mucosal Atomization Device is an optimal tool that can achieve rapid absorption into the CNS and the bloodstream across mucosal membranes. This study was designed to evaluate and compare the bioavailability of DXM and MEP after intranasal versus intravenous administration. Two open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover studies were conducted, which involved healthy male and female adult volunteers. After intranasal administration, DXM and MEP were detected in plasma after the first sampling time. Mean peak concentrations of DXM and MEP were 86.61 ng/mL at 60 min and 843.2 ng/mL at 1.5 h post-administration, respectively. DXM and MEP showed high absolute bioavailability, with values of 80% and 95%, respectively. No adverse effects were observed. DXM and MEP systemic bioavailability by intranasal administration was comparable with the intravenous one, suggesting that the intranasal route can be used as a non-invasive and appropriate alternative for systemic drug delivery.

Anti-N-methyl-D-aspartate receptor encephalitis: An observational and comparative study in Mexican children and adults.

OBJECTIVE: To present a case series of encephalitis patients with anti-N-methyl-D-aspartate receptor antibodies, attending two neurological referral centers in a three-year period. METHODS: A retrospective, descriptive, comparative study included child and adult patients in two neurological populations, positive for antibodies against the NR1 and NR2 subunits of the glutamate (NMDA) receptor in serum and CSF, as determined during a three-year period. RESULTS: Sixty-six patients were included (40 children and 26 adults). Male patients were more affected (M: F ratio was 1:0.6). No differences in progression or hospitalization time were observed between groups. In children, 35% of patients showed herpetic infection before autoimmune encephalitis (P = 0.01). Among viral prodromal symptoms, upper respiratory tract infection (P = 0.02) and fever (P = 0.001) predominated in children, while infectious gastroenteritis was more frequent in adults (P = 0.03). Among neuropsychiatric signs, mental confusion (P = 0.0001) and orofacial dyskinesia/oromandibular dystonia (P = 0.0001) were frequent in children, while emotional lability (P = 0.03), catatonia (P = 0.0001), and headache (P = 0.005) predominated in adults. The score in the modified Rankin scale on admission was higher in children (4.3 ± 0.8 vs. 2.2 ± 1.3, P = 0.0001), but at one-year of clinical follow up no significant differences were found. CONCLUSIONS: Male patients were predominantly affected in our population. One-third of all patients developed prodromal infection. Neuropsychiatric clinical complaints were different in children and adults. However, post-hospitalization recovery was similar between groups.

Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis.

The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n = 10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n = 11) and PTB (n = 27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.

A Comprehensive Analysis of COVID-19 Impact in Latin America.

Background: Latin America has now become the epicenter of the global coronavirus disease 2019 (COVID-19) pandemic. In the ongoing COVID -19 pandemic, a profound burden of SARS-COV-2 infection has been reported in Latin America. In the present study, we aim to determine the profiles that are associated with this disease in Latin America. We analyzed symptoms, morbidities and gastrointestinal (GI) manifestations by country. Methods: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 Latin American countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia between March 1 and July 30, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and lethality were performed. Results: A total of 728,282 patients tested positive for COVID-19 across all the 8 Latin American countries. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years old and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivia had fever as the top symptom (83.3%). GI symptoms including diarrhea (highest in Mexico with 22.9%), nausea, vomiting, and abdominal pain were not associated with higher mortality.Hypertension was among the top (12.1%) comorbidities followed by diabetes with 8.3% and obesity 4.5%. In multivariable analyses, the leading and significant comorbidities were hypertension (r=0.83, p=0.02), diabetes (r=0.91, p=0.01), and obesity (r=0.86, p=0.03). Asthma (r=0.37, p=0.54) and increasing age (0.13 p=0.81) were not independently associated with higher mortality. Lethality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Conclusion: Nearly, 10.5%-53% of patients with COVID-19 have GI manifestations. Differential clinical symptoms were associated with COVID-19 in Latin America countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed. Country-specific management and prevention plans can be established from this meta-analysis.

Challenges in the management of Covid-19 patients in a neurological center in Mexico City.

Not available.

Cognitive impairment in patients with central nervous system tuberculosis.

INTRODUCTION: Tuberculosis (TB) in Mexico remains an important cause of morbidity and mortality; in the past 4 years, 110,681 cases of pulmonary tuberculosis and 1571 cases of tuberculous meningitis were reported. OBJECTIVE: To determine the neurocognitive sequelae, clinical presentation and neuroimaging alterations in patients with central nervous system tuberculosis. METHODS: A retrospective, analytical, and cross-sectional study was carried out from 2010 to 2019. Patients with central nervous system tuberculosis, with and without HIV/AIDS coinfection, were included. RESULTS: During the study period, 104 cases with a definitive or probable central nervous system tuberculosis diagnosis were included; 38% had HIV/AIDS coinfection, and 55%, various comorbidities (p = 0.0001); 49% had cognitive alterations, and 14% died. CONCLUSIONS: Although HIV/AIDS infection can contribute to cognitive decline in patients with tuberculous meningitis, no differences were observed between patients with and without HIV/AIDS. Cognitive sequelae showed improvement during follow-up with adequate management and therapeutic control of the patients.

INTRODUCCIÓN: La tuberculosis en México sigue siendo causa importante de morbimortalidad; en los últimos cuatro años, se reportaron 110 681 casos de tuberculosis pulmonar y 1571 casos de tuberculosis meníngea. OBJETIVO: Determinar las secuelas neurocognoscitivas, presentación clínica y alteraciones en los estudios de neuroimagen en pacientes con tuberculosis del sistema nervioso central. MÉTODOS: Se realizó un estudio retrospectivo, analítico y transversal de 2010 a 2019. Se incluyeron pacientes con tuberculosis del sistema nervioso central, con y sin coinfección por VIH/sida. RESULTADOS: Durante el periodo de estudio se incluyeron 104 casos con diagnóstico definitivo y probable de tuberculosis del sistema nervioso central; de acuerdo con los criterios de Marais, 38 % presentó coinfección por VIH/sida y 55 %, diversas comorbilidades (p = 0.0001); 49 % presentó alteraciones cognoscitivas y 14 % falleció. CONCLUSIONES: Aunque la infección por VIH/sida puede contribuir al deterioro cognitivo del paciente con tuberculosis meníngea, no se observaron diferencias entre pacientes con y sin VIH/sida. Las secuelas cognoscitivas mostraron mejoría en el seguimiento con el adecuado manejo y control terapéutico de los pacientes.

Neglected and (re-)emergent infections of the CNS i n low-/middle-income countries.

Low- and middle-income countries (LMIC) have suffered from long-term health system deficiencies, worsened by poor living conditions, lack of sanitation, a restricted access to health facilities and running water, overcrowding, and overpopulation. These factors favor human displacement and deepen marginalization; consequently, their population endures a high burden of infectious diseases. In this context, the current epidemiological landscape and its impact on health and economic development are not promissory, despite the commitment by the international community to eradicate neglected tropical infections - especially tuberculosis and malaria, by 2030. Neglected and (re)-emerging infectious diseases affecting the central nervous system (CNS) are a major public health concern in these countries, as they cause a great morbidity and mortality; furthermore, survivors often suffer from severe neurological disabilities. Herein, we present a retrospective review focused on some neglected and (re)-emerging infectious diseases, including neurocysticercosis, malaria, rabies, West Nile virus encephalitis, tuberculosis, neuroborreliosis, and SARS-CoV-2 in LMIC. A retrospective review of studies on selected neglected and (re)-emerging infectious diseases in LMIC was performed, including reports by the World Health Organization (WHO) published within the last five years. Data on infection by SARS-CoV-2 were provided by the John Hopkins University Coronavirus Resource Center. CNS neglected and (re)-emerging infectious diseases remain as important causes of disease in LMIC. An alarming increase in the prevalence of malaria, tuberculosis, and cysticercosis is observed in the region, compounded by the recent COVID-19 pandemic. The WHO is currently supporting programs/efforts to cope with these diseases. Herein, we highlight the epidemiological burden of some CNS infections in LMIC, and their clinical and neuroimaging features, to facilitate an accurate diagnosis, considering that most of these diseases will not be eradicated in the short term; instead, their incidence will likely increase along with poverty, inequality, and related socioeconomic problems.

A Comprehensive Meta-Analysis of COVID-19 in Latin America.

Background: Latin America has become the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. We aim to perform a systematic comparative review of the clinical characteristics that are associated with this disease in Latin American countries. Methods: We conducted a systematic review of published articles, journal and/or epidemiological reports of confirmed COVID-19 cases in Latin America. Data were obtained either through publicly available information from Ministries of Health, published journal reports and/or unpublished datasets. We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia, between March 1st and July 30th, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities, and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and mortality were performed. Results: A total of 728,282 COVID-19 patients were included in this study. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivian patients had fever as the top symptom (83.3%). GI symptoms included diarrhea which was highest in Mexico with 22.9%. Hypertension was among the top (12.1%) comorbidities, followed by diabetes with 8.3% and obesity at 4.5%. In multivariate analyses, the leading and significant comorbidities were hypertension (r = 0.83, p = 0.02), diabetes (r = 0.91, p = 0.01), and obesity (r = 0.86, p = 0.03). Mortality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Conclusion: Overall, COVID-19 patients in Latin America display cough, fatigue, and fever as main symptoms. Up to 53% of patients with COVID-19 have GI manifestations. Different clinical symptoms were associated with COVID-19 in Latin American countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed and can be established from this meta-analysis.

Role of Systemic and Nasal Glucocorticoid Treatment in the Regulation of the Inflammatory Response in Patients with SARS-Cov-2 Infection.

The Chinese outbreak of SARS-CoV-2 during 2019 has become pandemic and the most important concerns are the acute respiratory distress syndrome (ARDS) and hyperinflammation developed by the population at risk (elderly and/or having obesity, diabetes, and hypertension) in whom clinical evolution quickly progresses to multi-organ dysfunction and fatal outcome. Immune dysregulation is linked to uncontrolled proinflammatory response characterized by the release of cytokines (cytokines storm). A proper control of this response is mandatory to improve clinical prognosis. In this context, glucocorticoids are able to change the expression of several genes involved in the inflammatory response leading to an improvement in acute respiratory distress. Although there are contradictory data in the literature, in this report we highlight the potential benefits of glucocorticoids as adjuvant therapy for hyperinflammation control; emphasizing that adequate dosage, timing, and delivery are crucial to reduce the dysregulated peripheral-and neuro-inflammatory response with minimal adverse effects. We propose the use of the intranasal route for glucocorticoid administration, which has been shown to effectively control the neuro-and peripheral-inflammatory response using low doses without generating unwanted side effects.

Reconversion of neurosurgical practice in times of the SARS-CoV-2 pandemic: a narrative review of the literature and guideline implementation in a Mexican neurosurgical referral center.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has forced the modification of surgical practice worldwide. Medical centers have been adapted to provide an efficient arrangement of their economic and human resources. Although neurosurgeons are not in the first line of management and treatment of COVID-19 patients, they take care of patients with neurological pathology and potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, the authors describe their institutional actions against the pandemic and compare these actions with those in peer-reviewed publications. METHODS: The authors conducted a search using the MEDLINE, PubMed, and Google Scholar databases from the beginning of the pandemic until July 11, 2020, using the following terms: "Neurosurgery," "COVID-19/SARS-CoV-2," "reconversion/modification," "practice," "academy," and "teaching." Then, they created operational guidelines tailored for their institution to maximize resource efficiency and minimize risk for the healthcare personnel. RESULTS: According to the reviewed literature, the authors defined the following three changes that have had the greatest impact in neurosurgical practice during the COVID-19 pandemic: 1) changes in clinical practices; 2) changes in the medical care setting, including modifications of perioperative care; and 3) changes in the academic teaching methodology. CONCLUSIONS: The Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez" is one of the major referral centers for treating highly complex neurosurgical pathologies in Mexico. Its clinical and neurosurgical practices have been modified with the implementation of specific interventions against the spread of COVID-19. These practical and simple actions are remarkably relevant in the context of the pandemic and can be adopted and suited by other healthcare centers according to their available resources to better prepare for the next event.