Regional epidemic dynamics and Delta variant diversity resulted in varying rates of spread of Omicron-BA.1 in Mexico (preprint)

The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In Mexico, this subvariant 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 the country. Unlike previous SARS-CoV-2 variants, BA.1 did not acquire local substitutions nor exhibited a geographically distinct circulation pattern in Mexico. However, a regional difference in the speed of the replacement of the Delta variant was observed, as some northern states showed persistence of Delta lineages well into February 2022. Mexican states were divided into four regions (North, Central North, Central South, and Southeast) based on the lineage circulation before the dominance of BA.1 to study possible causes for this difference. For each region, the time to fixation of BA.1, the diversity of Delta sublineages in the weeks preceding BA.1 entry, the population density, and the level of virus circulation during the inter-wave interval were determined. An association between a faster Omicron spread and lower Delta diversity, as well as fewer COVID-19 cases during the Delta-BA.1.x inter-wave period, was observed. For example, the North region exhibited the slowest spread but had the highest diversity of Delta sublineages and the greatest number of inter-wave cases relative to the maximum amount of the virus circulating in the region, whereas the Southeast region showed the opposite. 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. Nonetheless, if there is a significant difference in the fitness of the variants or the time allowed for the competition is sufficient, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico. Impact statementThe surveillance of lineage circulation of SARS-CoV-2 has helped identify variants that have a transmission advantage and are of concern to public health and to track the virus dispersion accurately. However, many factors contributing to differences in lineage spread dynamics beyond the acquisition of specific mutations remain poorly understood. In this work, a description of BA.1 entry and dispersion within Mexico is presented, and which factors potentially affected the spread rates of the Omicron variant BA.1 among geographical regions in the country are analyzed, underlining the importance of population density, the proportion of active cases, and viral lineage diversity and identity before the entry of BA.1. Data summaryThis work was carried out using data shared through the GISAID initiative. All sequences and metadate are available through GISAID with the accession EPI_SET_220927gw, accession numbers and metadata are also reported in the supplemental material of this article. Epidemiological data was obtained though the Secretaria de Salud website (https://www.gob.mx/salud/documentos/datos-abiertos-152127),

Clinical and Virological Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in Vaccinated and Unvaccinated Patients in Mexico City (preprint)

Background: Coronavirus disease 2019 (COVID-19) vaccines are very effective at protecting against severe disease and death. However, the impact of the vaccine used, viral variants, and host factors on disease severity in vaccinated individuals remain poorly understood. Here we compared COVID-19 clinical presentations and outcomes in vaccinated and unvaccinated patients in a tertiary hospital in Mexico City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were also determined to study their potential impact on disease severity. Methods: From March to September 2021, clinical and demographic characteristics were obtained from 1,014 individuals with a documented SARS-CoV-2 infection, and viral variants were identified in a subset of 386 patients. We compared three groups of patients: 1) unvaccinated, 2) partially vaccinated, and 3) fully vaccinated, stratifying by age groups (<30 years, 31-60 years, and > 61 years) on the clinical outcomes, and including in-hospital mortality. We fitted different multivariate statistical models to evaluate the impact of vaccination status, SARS-CoV-2 lineages, vaccine types, and clinical parameters. Results: 1,014 patients were included, with 11% being outpatients and 88% hospitalized. 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%). The percentage of critical patients over 61 years was higher in unvaccinated than vaccinated individuals (75% vs. 56%, p < 0.001). We found immune disease (OR: 3.12, 95% CI: 1.09-8.34, p = 0.02) and age above 61 years old (OR: 3.51, 95% CI: 2.3-5.2, p = 5.9e-10) as risk factors. While fully vaccination was found as the most protective factor against in-hospital death (OR: 0.25, 95% CI: 0.12-0.46, p = 2.89e-05). Conclusions: This study suggests that vaccination and particularly full vaccination is essential to reduce mortality in a comorbid population such as that of Mexico. When analyzing the presence of comorbidities and advanced ages as risk factors, complete vaccination was the most significant protective factor against death by COVID-19. We found no strong association between SARS-CoV-2 lineages or vaccine type and disease severity.

Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes (preprint)

COVID-19 outbreak has caused over 3 million deaths worldwide. Understanding disease pathology 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 particularly important since it’s known that the respiratory microbiota interacts 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 with healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure across study groups and correlated the results with clinical data. We found differences in diversity and abundance of bacteria between groups, higher levels of dysbiosis in the respiratory microbiota of COVID-19 patients (regardless of severity level), differences in diversity structure among mild, severe, and fatal COVID-19, and the presence of specific bacteria that correlated with clinical variables associated with increased mortality risk. Our data suggest that host-related and environmental factors could be affecting the respiratory microbiota before SARS-CoV-2 infection, potentially compromising the immunological response of the host against disease and promoting secondary bacterial infections. For instance, the high levels of dysbiosis coupled with low microbial structural complexity in the respiratory microbiota of COVID-19 patients, possibly resulted from antibiotic uptake and comorbidities, could have consequences for the host and microbial community level. Altogether, our findings identify the respiratory microbiota as a potential factor associated with COVID-19 severity.

Emergence and spread of the potential variant of interest (VOI) B.1.1.519 predominantly present in Mexico. (preprint)

SARS-CoV-2 variants have emerged in late 2020 and there are at least three variants of concern (B.1.1.7, B.1.351, P1) reported by WHO. These variants have several substitutions in the Spike protein that affect receptor binding; they present increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we are reporting 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, which rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.

Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial. (preprint)

Health care workers are at high risk of being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Our aim is to evaluate the efficacy and safety of hydroxychloroquine (HCQ) for prophylaxis of COVID19 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 COVD19 patients. Main outcome was time to symptomatic SARS-CoV2 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 = 0.09). No severe COVID19 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: Although the number of symptomatic infections in health personnel was lower in the HCQ group, the difference was not statistically significant. The trial is underpowered due to the failure to complete the estimated sample size.