Faculty Bibliography

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.ajpath.2020.07.001. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

The dynamics of viral load (VL) of the 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2) and its association with different clinical parameters remain poorly characterized in the US patient population. Herein, we investigate associations between VL and parameters, such as severity of symptoms, disposition (admission versus direct discharge), length of hospitalization, admission to the intensive care unit, length of need for oxygen support, and overall survival in a cohort of 205 patients from a tertiary care center in New York City. VL was determined using quantitative PCR and log10 transformed for normalization. Univariate and multivariate regression models were used to test these associations. We found that diagnostic viral load is significantly lower in hospitalized patients than in patients not hospitalized (log10 VL = 3.3 versus 4.0; P = 0.018) after adjusting for age, sex, race, body mass index, and comorbidities. Higher VL was associated with shorter duration of the symptoms in all patients and hospitalized patients only and shorter hospital stay (coefficient = -2.02, -2.61, and -2.18; P < 0.001, P = 0.002, and P = 0.013, respectively). No significant association was noted between VL, admission to intensive care unit, length of oxygen support, and overall survival. Our findings suggest a higher shedding risk in less symptomatic patients, an important consideration for containment strategies in severe acute respiratory syndrome coronavirus 2. Furthermore, we identify a novel association between viral load and history of cancer. Larger studies are warranted to validate our findings.

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.

Background: The Mediator Complex (MED) is a large multi-subunit protein which interacts directly with RNA Polymerase II and transcription factors for general regulation of protein expression. Recently, Mediator Complex 7 (MED7) has been shown to be underexpressed in high grade invasive mammary carcinomas in comparison to lower grade invasive carcinomas. No study has yet investigated the expression of MED7 in ductal carcinoma in situ (DCIS). In our study, we set out to evaluate the biological significance of MED7 in DCIS.
Design(s): MED7 immunostaining was performed with a rabbit monoclonal antibody (EPR15410, Abcam- Ab187146, Cambridge, UK). The H-score method was utilized for quantifying MED7 nuclear expression in DCIS. This method combines nuclear staining intensity and the percentage of positive cells. Staining intensity (0-3) is multiplied by percentage of positive DCIS cells (0-100) leading to the H-score, with a range of 0-300 for each case. We investigated breast core biopsies with DCIS; 20 were high grade, 14 were intermediate grade, and 15 were low grade. The hormone receptor status of each case was also recorded. GraphPad PRISM 7.0 software was used for statistical analysis.
Result(s): The mean H-Score for high grade DCIS cases was 146, intermediate grade was 219, and low grade was 228 (p <0.0001, Kruskal-Wallis test). The mean H-score for high grade DCIS cases was significantly lower than that of low and intermediate grade DCIS (p <0.0001 and p = 0.0004, respectively, Dunn's test). The MED7 H-Score was significantly lower in ER negative cases compared to that seen in ER positive cases (p <0.0001). Area under the curve (AUC) in the ROC curve for MED7 H-Scores in high grade versus non-high grade DCIS cases was 0.9276 (p <0.0001). (Table presented)
Conclusion(s): Our results suggest that MED7 expression is significantly down regulated in high grade and ER-negative DCIS cases, thus implying a significant biological role of MED7 in the progression of DCIS. Taken together, our data establishes MED7 H-score as a tangible tool for evaluating high grade DCIS. Further studies are underway to establish a practical cut-off value for the MED7 H-Score for high grade DCIS. We believe that these important early steps investigating MED7 are crucial in clarifying its important role in the development and progression of breast and other cancers