Longitudinal Characterization of a Neutralizing and Total Antibody Response in Patients with Severe COVID-19 and Fatal Outcomes.

The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations in severe COVID-19 cases. Until now, the importance of developing a neutralizing antibody response in the acute phase and its relationship with progression to severe disease or fatal outcome among hospitalized patients remains unclear. In this study, we aim to characterize and compare longitudinally the primary humoral immune host response in the early stages of the disease, looking for an association between neutralization, antibody titers, infective viral lineage, and the clinical outcome in hospitalized and non-hospitalized patients. A total of 111 patients admitted at INER from November 2021 to June 2022 were included. We found that patients with negative or low neutralization showed a significant reduction in survival probability compared to patients with medium or high neutralization. We observed a significant decrease in the median of neutralization in patients infected with viral variants with changes in RBD of the spike protein. Our results suggest that developing an early and robust neutralizing response against SARS-CoV-2 may increase survival probability in critical patients.

A(H3N2) antigenic variation of influenza is associated with low vaccine efficacy in the early 2018 influenza season in Mexico City.

OBJECTIVES: We evaluated the VE and the mutations of the viruses present in the Mexican population at the beginning of 2018. METHODS: We diagnosed influenza in outpatients with a high-performance Rapid Influenza Diagnostic Test (RIDT) qRT-PCR. Descriptive statistics were used to describe the study population, while the chi-square test was used to determine clinical variables. VE was analyzed through a negative test design. We sequenced the hemagglutinin (HA) gene, performed a phylogenetic analysis, and analyzed the nonsynonymous substitutions both in and outside antigenic sites. RESULTS: Of the 240 patients analyzed, 42.5% received the trivalent vaccine, and 37.5% were positive for influenza. The VE for the general population for any influenza virus type or subtype was 37.0%, while the VE for the predominant influenza A(H3N2) subtype was the lowest (19.7%). The phylogenetic analysis of HA showed the co-circulation of clades and subclades 3C.2a1, 3C.2a1b, 3C.2a2, 3C.2a2re, 3C.2a3, and 3C.3a with identities approximately 97-98% similar to the vaccine composition. CONCLUSION: Low VE was related to the co-circulation of multiple clades and subclades of influenza A(H3N2), with sufficient genetic and phenotypic distance to allow for the infection of vaccinated individuals.

Ivermectin: A Controversial Focal Point during the COVID-19 Pandemic.

The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. The challenge the world is facing is that of trying to find a possible treatment, and a viable and expedient option for addressing this challenge is the repurposing of drugs. However, in some cases, although these drugs are approved for use in humans, the mechanisms of action involved are unknown. In this sense, to justify its therapeutic application to a new disease, it is ideal, but not necessary, to know the basic mechanisms of action involved in a drug's biological effects. This review compiled the available information regarding the various effects attributed to Ivermectin. The controversy over its use for the treatment of COVID-19 is demonstrated by this report that considers the proposal unfeasible because the therapeutic doses proposed to achieve this effect cannot be achieved. However, due to the urgent need to find a treatment, an exhaustive and impartial review is necessary in order to integrate the knowledge that exists, to date, of the possible mechanisms through which the treatment may be helpful in defining safe doses and schedules of Ivermectin.

Risk of Pulmonary Fibrosis and Persistent Symptoms Post-COVID-19 in a Cohort of Outpatient Health Workers.

Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5−3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.

Cigarette Smoking Alters the Expression of Circulating microRNAs and Its Potential Diagnostic Value in Female Lung Cancer Patients.

Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS-), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS-), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS- patients from H/CS- controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Socioeconomic factors influencing hospitalized patients with pneumonia due to influenza A(H1N1)pdm09 in Mexico.

BACKGROUND: In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. METHODOLOGY AND PRINCIPAL FINDINGS: A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. CONCLUSIONS: Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These socioeconomic factors may explain the different patterns of morbidity and mortality for H1N1 influenza observed among different countries and regions.

[An unusual outbreak of histoplasmosis in residents of the state of Mexico]. / Brote inusual de histoplasmosis en residentes del estado de México.

OBJECTIVE: The aim of this study was to establish whether there was a histoplasmosis outbreak among a group of residents of Naucalpan (State of Mexico, a non-endemic area for histoplasmosis) and to ascertain the source through which they were infected. MATERIAL AND METHODS: Anyone associated with the Index Case in the same period with a flu-like infection was considered as a suspected case. Diagnosis was confirmed by clinical examination positive, cultures and positive immunological tests. Date and form of potential exposure were obtained through interviews. Material potentially contaminated with bird or bat droppings was sought and analyzed by PCR. RESULTS: The outbreak was associated with a trip to El Tamarindo (Veracruz, near the Gulf of Mexico). Patients got sick after digging a hole in the floor inside a house where a treasure had been supposedly buried by a death relative. The pathogen was detected in soil samples at 10 cm below the surface. CONCLUSIONS: The study showed that patients contracted histoplasmosis in El Tamarindo, a community where there had been no prior cases of this disease.

Reducing occurrence and severity of pneumonia due to pandemic H1N1 2009 by early oseltamivir administration: a retrospective study in Mexico.

BACKGROUND: Anti-viral treatment has been used to treat severe or progressive illness due to pandemic H1N1 2009. A main cause of severe illness in pandemic H1N1 2009 is viral pneumonia; however, it is unclear how effective antiviral treatment is against pneumonia when administered >48 hours after symptom onset. Therefore, we aimed to determine how time from symptom onset to antiviral administration affected the effectiveness of antiviral treatment against pneumonia due to pandemic (H1N1) 2009. METHODS/PRINCIPAL FINDINGS: A retrospective medical chart review of 442 patients was conducted in a hospital in Mexico. Subjects had tested positive for pandemic H1N1 2009 virus by real-time reverse-transcriptase-polymerase-chain-reaction and were administered oseltamivir. Median time from symptom onset to oseltamivir administration was 5.0 days (range, 0-43). 442 subjects, 71 (16.1%) had severe pneumonia which required mechanical ventilation, 191 (43.2%) had mild to moderate pneumonia, and 180 (40%) did not have pneumonia. Subjects were divided into four groups based on time to oseltamivir administration: ≤2, 3-7, 8-14, and >14 days. Severity of respiratory features was associated with time to treatment, and multivariate analysis indicated that time to oseltamivir administration was associated with severity of respiratory features. A proportional odds model indicated that 50% probability for occurrence of pneumonia of any severity and that of severe pneumonia in patients who would develop pneumonia reached at approximately 3.4 and 21 days, respectively, after symptom onset. Patients with a shorter time to oseltamivir administration were discharged earlier from the hospital. CONCLUSIONS: Earlier initiation of oseltamivir administration after symptom onset significantly reduced occurrence and severity of pneumonia and shortened hospitalization due to pandemic H1N1 2009. Even when administered >48 hours after symptom onset, oseltamivir showed considerable potential for reducing pneumonia. Application of these results would benefit patients affected by future influenza pandemics.

Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-control study in Mexico City.

OBJECTIVE: To evaluate the association of 2008-9 seasonal trivalent inactivated vaccine with cases of influenza A/H1N1 during the epidemic in Mexico. DESIGN: Frequency matched case-control study. SETTING: Specialty hospital in Mexico City, March to May 2009. PARTICIPANTS: 60 patients with laboratory confirmed influenza A/H1N1 and 180 controls with other diseases (not influenza-like illness or pneumonia) living in Mexico City or the State of Mexico and matched for age and socioeconomic status. MAIN OUTCOME MEASURES: Odds ratio and effectiveness of trivalent inactivated vaccine against influenza A/H1N1. RESULTS: Cases were more likely than controls to be admitted to hospital, undergo invasive mechanical ventilation, and die. Controls were more likely than cases to have chronic conditions that conferred a higher risk of influenza related complications. In the multivariate model, influenza A/H1N1 was independently associated with trivalent inactivated vaccine (odds ratio 0.27, 95% confidence interval 0.11 to 0.66) and underlying conditions (0.15, 0.08 to 0.30). Vaccine effectiveness was 73% (95% confidence interval 34% to 89%). None of the eight vaccinated cases died. CONCLUSIONS: Preliminary evidence suggests some protection from the 2008-9 trivalent inactivated vaccine against pandemic influenza A/H1N1 2009, particularly severe forms of the disease, diagnosed in a specialty hospital during the influenza epidemic in Mexico City.

Simulacro ante una pandemia de influenza en el Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas / Simulacrum at The National Institute of Respiratory Diseases in the presence of an influenza pandemia

La influenza, enfermedad respiratoria altamente contagiosa causada por un influenza virus, se ha presentado desde tiempos remotos. En tiempos de Hipócrates se describieron eventos con todas las características de probables epidemias de influenza sucedidas en la época helénica. El término se originó en Italia, siglo XV, pues las epidemias sucedidas en esa época se atribuían a la "influencia de las estrellas". No se puede determinar cuándo ocurrirá una pandemia; sin embargo, se sabe que se presenta con cierta regularidad. La primera epidemia de influenza descrita como tal y generalmente aceptada, ocurrió en Europa en diciembre de 1173; la primera pandemia descrita que afectó a Europa, Asia y el Norte de África fue en 1580, y la primera que afectó al Continente Americano ocurrió en 1647¹. Es por ello que la Organización Mundial de la Salud solicitó a los países participantes desarrollar los planes de preparación y respuesta para hacer frente a esta eventualidad. México participa por medio de numerosas entidades a nivel federal, instituciones y organismos nacionales con el objeto de proteger a la población de una pandemia mediante acciones efectivas y oportunas. El Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, desarrolló una estrategia propia basándose en las seis líneas de acción contenidas en el Plan Nacional, lo que le permitirá tener las guías y elementos necesarios para formular su propio Plan de Preparación y Respuesta ante una Pandemia de Influenza. Las seis líneas de acción de acuerdo con el Plan Nacional son: 7. Difusión y comunicación social, 2. Coordinación, 3. Vigilancia epidemiológica, 4. Atención médica, 5. Reserva estratégica y 6. Investigación y desarrollo. Se describen los preparativos, curso y resultados de un simulacro de pandemia de influenza.

Influenza is a highly contagious disease caused by a virus; the disease is known since the times of Hippocrates, who described events with all the characteristics of influenza epidemics during his times. Apparently, the term was coined in Italy during the XV century because the disease was attributed to the "influence" of the stars. The first formally described influenza epidemic probably dates back to December 1173; the first pandemic, in 1580, affected Europe, Asia and North Africa; the first affecting the American Continent occurred in 1647. The countries from the WHO have been asked to develop plans to face the real possibility of a new pandemic, this caused by an avian virus; Mexico has participated through the joint effort of many institutions at federal, state and municipal levels, including the Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (National Institute of Respiratory Diseases) were we have developed a strategy of six lines of action to face this pandemia: Diffusion and social communication, coordination, epidemiologic surveillance, medical services, strategic reserve, development and research. The preparations, course and results of an influenza pandemic simulacrum are described.

Brote por Salmonella enteritidis en trabajadores de un hospital / An outbreak of Salmonella gastroenteritis among hospital worker

Objetivo. Describir y determinar las causas de un brote de enfermedad gastrointestinal por Salmonella enteritidis, ocurrido en junio de 1998, entre el personal trabajador de la salud (TS) que labora en un hospital de tercer nivel de atención, en la ciudad de México. Material y métodos. Se incluyó a todo aquel empleado que presentó diarrea o fiebre asociada a síntomas gastrointestinales, a partir del día 8 de junio de ese año, posterior a la ingestión de alimentos en el comedor del hospital (caso), y en aquellos asintomáticos (controles) que ingirieron alimentos durante el mismo periodo y en el mismo lugar. Se les aplicó un cuestionario para conocer los alimentos ingeridos, se realizó hemocultivo a sujetos con fiebre mayor de 38 ºC y coprocultivo a todos, incluido el personal de la cocina. En el análisis estadístico se utilizó razón de momios (RM), intervalos de confianza al 95 por ciento (IC 95 por ciento), ji cuadrada y valor de p= 0.05 para conocer la significancia estadística. Resultados. Desarrollaron síntomas 155 TS, y de éstos 129 completaron la encuesta; se encuestaron además 150 TS asintomáticos. Los síntomas más comunes fueron diarrea (85 por ciento), dolor abdominal (84 por ciento), cefalea (81.4 por ciento), náusea (78.3 por ciento) y escalofríos (74.4 por ciento). Ocho hemocultivos fueron negativos; 59 casos (46 por ciento) y seis controles (4 por ciento) tuvieron coprocultivos positivos a Salmonella enteritidis. De los alimentos ingeridos, las tortas de carne capeadas con huevo (RM 19.39, IC 95 por ciento 9.09-41.4), la crema de mamey, así como el yogur fueron significativamente más frecuentes en casos que en controles. Los cultivos de los alimentos resultaron negativos. Conclusión. Muy probablemente este brote se debió a la ingestión de alimentos contaminados (tortas preparadas con huevo, papa y carne) con insuficiente cocción. Este brote enfatiza la necesidad de mantener un programa de evaluación de la calidad de los alimentos en hospitales. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html