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ntary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.
In early 2020, Ecuador reported one of the highest surges of per capita deaths across the globe.
We collected a comprehensive dataset containing individual death records between 2015 and 2020 from the Ecuadorian National Institute of Statistics and Census and the Ecuadorian Ministry of Government. We computed the number of excess deaths across time, geographical locations and demographic groups using Poisson regression methods.
Between January 1
and September 23
, 2020, the number of excess deaths in Ecuador is 36,402 (95% CI 35,762-36,827) or 208 per 10
population, which is 171% of the expected deaths in that period in a typical year. Only 20% of the excess deaths are attributable to confirmed COVID-19 deaths. Strikingly, in provinces that were most affected by COVID-19, such as Guayas and Santa Elena, the all-cause deaths are more than double the expected number of deaths that would have occurred in a normal year. The extent of excess deaths in men is higher than in women, and the number of excess deaths increases with age. Indigenous populations had the highest level of excess deaths among all ethnic groups.
Overall, the exceptionally high level of excess deaths in Ecuador highlights the enormous burden and heterogeneous impact of COVID-19 on mortality especially in older age groups and indigenous populations in Ecuador that was not fully revealed by COVID-19 death counts. Together with the limited testing in Ecuador, our results suggest that the majority of the excess deaths were likely to be undocumented COVID-19 deaths.
Overall, the exceptionally high level of excess deaths in Ecuador highlights the enormous burden and heterogeneous impact of COVID-19 on mortality especially in older age groups and indigenous populations in Ecuador that was not fully revealed by COVID-19 death counts. Together with the limited testing in Ecuador, our results suggest that the majority of the excess deaths were likely to be undocumented COVID-19 deaths.
Sequencing of the SARS-CoV-2 viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.
SARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during November 22-December 2, 2020 and January 10-29, 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.
A total of 12,124 tests were performed yielding 1,099 positives. selleck chemicals From these, 811 high quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.9% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to "West Coast" variants were at higher risk of infection compared to household contacts exposed to lineages luring January 2021, suggesting its modestly higher transmissibility.
Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.
Ninety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.
Viral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m
(aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044).
We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.
We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence was 34%, with higher prevalence in children compared to adults. Having a seropositive household member was associated with a two-fold probability of individual seropositivity, suggesting a role for household transmission. Co-morbidities and preventive behaviors were not associated with SARS-CoV-2 seroprevalence.Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here we report that elevated interleukin-13 (IL-13) was associated with the need for mechanical ventilation in two independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab had less severe disease. In SARS-CoV-2 infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, in the lung, hyaluronan synthase 1 ( Has1 ) was the most downregulated gene and hyaluronan accumulation was decreased. Blockade of the hyaluronan receptor, CD44, reduced mortality in infected mice, supporting the importance of hyaluronan as a pathogenic mediator, and indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and hyaluronan has important implications for therapy of COVID-19 and potentially other pulmonary diseases.
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