Human amnion epithelial cell therapy reduces hypertension-induced vascular stiffening and cognitive impairment.

Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8-12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9-11, P < 0.05). Administration of amnion epithelial cells attenuated these effects of angiotensin II (P < 0.05). Angiotensin II-induced cognitive impairment was prevented by amnion epithelial cell therapy (n = 7-9, P < 0.05). In the brain, amnion epithelial cells modulated some of the inflammatory genes that angiotensin II promoted differential expression of (n = 6, p-adjusted < 0.05). These findings suggest that amnion epithelial cells could be explored as a potential therapy to inhibit vascular pathology and cognitive impairment during hypertension.

Variability in SARS-Cov-2 IgG Antibody Affinity To Omicron and Delta Variants in Convalescent and Community mRNA Vaccinated Individuals

The emergence of Omicron and Delta variants of SARS-CoV-2 has begun a number of discussions regarding breakthrough infection, waning immunity, need and timing for vaccine boosters and whether existing mRNA vaccines for the wildtype strain are adequate. Our work leverages a biosensor-based technique to evaluate the binding efficacy of SARS-CoV-2 S1 specific salivary antibodies to the Omicron and Delta variants using a cohort of mRNA vaccinated (n=109) and convalescent (n=19) subjects. We discovered a wide range of binding efficacies to the variant strains, with a mean reduction of 60.5%, 26.7%, and 14.7% in measurable signal to the Omicron strain and 13.4%, 2.4%, and -6.4% percent mean reduction to the Delta Variant for convalescent, Pfizer, and Moderna vaccinated groups respectively. This assay may be an important tool in determining susceptibility to infection or need for booster immunization as the pandemic evolves. Key PointsO_LIAMPERIAL assay developed to quantify salivary SARS-CoV-2 S1 IgG antibodies to Omicron and Delta variants C_LIO_LIThere was a reduction in affinity to both Delta and Omicron Variants C_LIO_LIThe reduction in affinity was more pronounced to Omicron than for Delta Variants C_LIO_LIThere was a significant difference between IgG affinities in Individuals vaccinated with Pfizer versus Moderna Vaccines C_LI

A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron

The rapid emergence of new SARS-CoV-2 variants raises a number of public health questions including the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to better understand patterns of transmission and possible load on healthcare resources. Next-Generation Sequencing (NGS) is the primary method for detecting and tracing the emergence of new variants, but it is expensive, and it can take weeks before sequence data is available in public repositories. Here, we describe a Polymerase Chain Reaction (PCR)-based genotyping approach that is significantly less expensive, accelerates reporting on SARS-CoV-2 variants, and can be implemented in any testing lab performing PCR. Specific Single Nucleotide Polymorphisms (SNPs) and indels are identified that have high positive percent agreement (PPA) and negative percent agreement (NPA) compared to NGS for the major genotypes that circulated in 2021. Using a 48-marker panel, testing on 1,128 retrospective samples yielded a PPA and NPA in the 96.3 to 100% and 99.2 to 100% range, respectively, for the top 10 most prevalent lineages. The effect on PPA and NPA of reducing the number of panel markers was also explored. In addition, with the emergence of Omicron, we also developed an Omicron genotyping panel that distinguishes the Delta and Omicron variants using four (4) highly specific SNPs. Data from testing demonstrates the capability to use the panel to rapidly track the growing prevalence of the Omicron variant in the United States in December 2021.

The Kinetics of COVID-19 Vaccine Response in a Community Vaccinated Population

We used a noninvasive electrochemical quantitative assay for IgG antibodies to SARS-CoV-2 S1 in saliva to investigate the kinetics of antibody response in a community-based population who had received either the Pfizer or Moderna mRNA-based vaccines. Samples were received from a total of 97 individuals including a subset of 42 individuals who collected samples twice-weekly for 3 months or longer. In all, 840 samples were collected and analyzed. In all individuals, salivary antibody levels rose sharply in the 2-week period following their second vaccination, with peak antibody levels being at 10-20 days post-vaccination. We observed that 20%, 10% and 2.4% of individuals providing serial samples had a 90%, 95%, and 99% drop respectively from peak levels during the duration of monitoring and two patients fell to pre-vaccination levels (5%). The use of non-invasive quantitative salivary antibody measurement can allow widespread, cost-effective monitoring of vaccine response. Article Summary LineCOVID-19 antibodies were measured in saliva and 20% of vaccinated subjects experienced a 90% drop in peak antibody levels over the course of monitoring.

Rapid displacement of SARS-CoV-2 variant B.1.1.7 by B.1.617.2 and P.1 in the United States

This study reports on the displacement of Alpha (B.1.1.7) by Delta (B.1.617.2 and its substrains AY.1, AY.2, and AY.3) in the United States. By analyzing RT-qPCR testing results and viral sequencing results of samples collected across the United States, we show that the percentage of SARS-CoV-2 positive cases caused by Alpha dropped from 67% in May 2021 to less than 3.0% in just 10 weeks. We also show that the Delta variant has outcompeted the Iota (B.1.526) variant of interest and Gamma (P.1) variant of concern. An analysis of the mean quantification cycles (Cq) values in positive tests over time also reveal that Delta infections lead to a higher viral load on average compared to Alpha infections, but this increase is only 2 to 3x on average for our study design. Our results are consistent with the hypothesis that the Delta variant is more transmissible than the Alpha variant, and that this could be due to the Delta variants ability to establish a higher viral load earlier in the infection compared to the Alpha variant.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Can the sequential use of conventional silicone oil and heavy oil be a strategy for the management of proliferative vitreoretinopathy?

<p><b>INTRODUCTION</b>Densiron is a novel long-term tamponade. Its specific gravity is 1.06 g/mL and as such it is heavier than water and provides support for the inferior retina. As proliferative vitreoretinopathy (PVR) has a propensity for the inferior retina, we used Densiron on a consecutive series of 97 cases with inferior pathology. We hypothesised that the sequential use of conventional and heavy silicone oil is a strategy for the management of PVR.</p><p><b>MATERIALS AND METHODS</b>A consecutive interventional case series involving the use of Densiron for PVR cases was studied. Patients were selected if conventional silicone oil and Densiron were used sequentially. Anatomical success was defined as total re-attachment in the absence of any tamponade agent for at least 3 months post oil removal.</p><p><b>RESULTS</b>Of the 97 patients, 10 patients fulfilled the criteria. Surgery involving Densiron was successful in re-attaching the retina in 7 of 10 cases, with one sequence of alternating light then heavy oil operation, and with one further surgery using silicone oil in the remaining 3 cases. The mean LogMAR preoperative vision was 1.57 and the postoperative vision was 0.82. In 8 of 10 patients, the final vision was 20/200 or better; in 5 of 10 patients, 20/80 or better. The mean follow-up was 19.5 months (range, 9 to 45).</p><p><b>CONCLUSIONS</b>The sequential use of conventional silicone oil and Densiron may be a strategy in reducing the number of re-operations. Our case series shows that despite multiple surgical procedures, favourable visual outcome can be achieved.</p>