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It is convenient to study complete genome sequences of human respiratory syncytial virus (hRSV) for ongoing genomic characterization and identification of highly transmissible or pathogenic variants. Whole genome sequencing of hRSV has been challenging from respiratory tract specimens with low viral loads. Herein, we describe an amplicon-based protocol for whole genome sequencing of hRSV subgroup A validated with 24 isolates from nasopharyngeal swabs and infected cell cultures, which showed cycle threshold (Ct) values ranging from 10 to 31, as determined by quantitative reverse-transcription polymerase chain reaction. MinION nanopore generated 3200 to 5400 reads per sample to sequence over 93% of the hRSV-A genome. Coverage of each contig ranged from 130× to 200×. Samples with Ct values of 20.9, 25.2, 27.1, 27.7, 28.2, 28.8, and 29.6 led to the sequencing of over 99.0% of the virus genome, indicating high genome coverage even at high Ct values. This protocol enables the identification of hRSV subgroup A genotypes, as primers were designed to target highly conserved regions. Consequently, it holds potential for application in molecular epidemiology and surveillance of this hRSV subgroup.

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Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered) and use of antibiotics differ in their microbial community composition. We found important differences in the diversity and composition of the microbiota between deceased and recovered patients. In particular, we detected a high abundance of opportunistic pathogens such as Granulicatella, in patients either deceased or with antibiotic treatment. Also, we found antibiotic treatment correlated with lower diversity of microbial communities and with lower probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.

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PURPOSE: The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In this work, a characterization of the spread of this variant in Mexico is presented. METHODS: The time to fixation of BA.1, the diversity of Delta sublineages, the population density, and the level of virus circulation during the inter-wave interval were determined to analyze differences in BA.1 spread. RESULTS: BA.1 began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in Mexico. Unlike previous variants, BA.1 did not exhibit a geographically distinct circulation pattern. However, a regional difference in the speed of the replacement of the Delta variant was observed. CONCLUSIONS: Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics, in addition to population density. Nonetheless, if there is a significant difference in the fitness of the variants, or if the time allowed for the competition is sufficiently long, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico.

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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.

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Coronavirus disease 2019 (COVID-19) vaccines effectively protect against severe disease and death. However, the impact of the vaccine used, viral variants, and host factors on disease severity remain poorly understood. This work aimed to compare COVID-19 clinical presentations and outcomes in vaccinated and unvaccinated patients in Mexico City. From March to September 2021, clinical, demographic characteristics, and viral variants were obtained from 1014 individuals with a documented SARS-CoV-2 infection. We compared unvaccinated, partially vaccinated, and fully vaccinated patients, stratifying by age groups. We also fitted multivariate statistical models to evaluate the impact of vaccination status, SARS-CoV-2 lineages, vaccine types, and clinical parameters. Most hospitalized patients were unvaccinated. In patients over 61 years old, mortality was significantly higher in unvaccinated compared to fully vaccinated individuals. In patients aged 31 to 60 years, vaccinated patients were more likely to be outpatients (46%) than unvaccinated individuals (6.1%). We found immune disease and age above 61 years old to be risk factors, while full vaccination was found to be the most protective factor against in-hospital death. This study suggests that vaccination is essential to reduce mortality in a comorbid population such as that of Mexico.

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INTRODUCTION: Health care workers are at high risk of being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our aim is to evaluate the efficacy and safety of hydroxychloroquine (HCQ) for prophylaxis of coronavirus disease 19 (COVID-19) in health personnel exposed to patients infected by SARS-CoV-2. METHODS: Double-blind randomized, placebo-controlled single center clinical trial. Included subjects were health care workers caring for severe COVID-19 patients. Main outcome was time to symptomatic SARS-CoV-2 infection. RESULTS: 127 subjects with a confirmed baseline negative RT-PCR SARS-CoV2 test were included in the trial. 62 assigned to HCQ and 65 to placebo. One subject (1.6%) in the HCQ group and 6 (9.2%) subjects in the placebo group developed COVID-19 (Log-Rank test p = 0.07). No severe COVID-19 cases were observed. The study was suspended because of a refusal to participate and losses to follow up after several trials reported lack of effectiveness of hydroxychloroquine in hospitalized patients with COVID-19. CONCLUSION: The effect size of hydroxychloroquine was higher than placebo for COVID-19 symptomatic infection in health personnel, although this was not statistically significant. The trial is underpowered due to the failure to complete the estimated sample size.

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During the first year of the SARS-CoV-2 pandemic in Mexico, more than two million people were infected. In this study, we analyzed full genome sequences from 27 February 2020 to 28 February 2021 to characterize the geographical and temporal distribution of SARS-CoV-2 lineages and identify the most common circulating lineages during this period. We defined six different geographical regions with particular dynamics of lineage circulation. The Northeast and Northwest regions were the ones that exhibited the highest lineage diversity, while the Central south and South/Southeast regions presented less diversity with predominance of a certain lineage. Additionally, by late February 2021, lineage B.1.1.519 represented more than 89% of all circulating lineages in the country.

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The COVID-19 outbreak has caused over three million deaths worldwide. Understanding the pathology of the disease and the factors that drive severe and fatal clinical outcomes is of special relevance. Studying the role of the respiratory microbiota in COVID-19 is especially important as the respiratory microbiota is known to interact with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared it to healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure between the study groups and correlated the results with clinical data. We found differences in the microbial composition for COVID-19 patients, healthy controls, and non-COVID-19 pneumonia controls. In particular, we detected a high number of potentially opportunistic pathogens associated with severe and fatal levels of the disease. Also, we found higher levels of dysbiosis in the respiratory microbiota of patients with COVID-19 compared to the healthy controls. In addition, we detected differences in diversity structure between the microbiota of patients with mild, severe, and fatal COVID-19, as well as the presence of specific bacteria that correlated with clinical variables associated with increased risk of mortality. In summary, our results demonstrate that increased dysbiosis of the respiratory tract microbiota in patients with COVID-19 along with a continuous loss of microbial complexity structure found in mild to fatal COVID-19 cases may potentially alter clinical outcomes in patients. Taken together, our findings identify the respiratory microbiota as a factor potentially associated with the severity of COVID-19.

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SARS-CoV-2 variants emerged in late 2020, and at least three variants of concern (B.1.1.7, B.1.351, and P1) have been reported by WHO. These variants have several substitutions in the spike protein that affect receptor binding; they exhibit increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we report the identification of a potential variant of interest, harboring the mutations T478K, P681H, and T732A in the spike protein, within the newly named lineage B.1.1.519, that rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.

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BACKGROUND: Data on short-term peripheral intravenous catheter-related bloodstream infections per 1,000 peripheral venous catheter days (PIVCR BSIs per 1,000 PVC days) rates from Latin America are not available, so they have not been thoroughly studied. METHODS: International Nosocomial Infection Control Consortium (INICC) members conducted a prospective, surveillance study on PIVCR BSIs from January 2010 to March 2018 in 100 intensive care units (ICUs) among 41 hospitals, in 26 cities of 9 countries in Latin America (Argentina, Brazil, Colombia, Costa Rica, Dominican-Republic, Ecuador, Mexico, Panama, and Venezuela). The Centers for Disease Control and Prevention (CDC) National Health Safety Network (NHSN) definitions were applied, and INICC methodology and INICC Surveillance Online System software were used. RESULTS: In total, 10,120 ICU patients were followed for 40,078 bed days and 38,262 PVC days. In addition, 79 PIVCR BSIs were identified, with a rate of 2.06 per 1,000 PVC days (95% confidence interval [CI], 1.635-2.257). The average length of stay (ALOS) of patients without a PIVCR BSI was 3.95 days, and the ALOS was 5.29 days for patients with a PIVCR BSI. The crude extra ALOS was 1.34 days (RR, 1.33; 95% CI, 1.0975-1.6351; P = .040).The mortality rate in patients without PIVCR BSI was 3.67%, and this rate was 6.33% in patients with a PIVCR BSI. The crude extra mortality was 1.70 times higher. The microorganism profile showed 48.5% gram-positive bacteria (coagulase-negative Staphylococci 25.7%) and 48.5% gram-negative bacteria: Acinetobacter spp, Escherichia coli, and Klebsiella spp (8.5% each one), Pseudomonas aeruginosa (5.7%), and Candida spp (2.8%). The resistances of Pseudomonas aeruginosa were 0% to amikacin and 50% to meropenem. The resistance of Acinetobacter baumanii to amikacin was 0%, and the resistance of coagulase-negative Staphylococcus to oxacillin was 75%. CONCLUSIONS: Our PIVCR BSI rates were higher than rates from more economically developed countries and were similar to those of countries with limited resources.

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