Healthcare workers (HCWs) are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes Coronavirus Disease (COVID-19). We aim to assess the seroprevalence of SARS-CoV-2 IgG among healthcare workers and compare risk-factors between seropositive and seronegative HCWs. In this observational study, serum samples were collected from HCWs between July 13th to 26th, 2020 at Boston Medical Center (BMC). Samples were subsequently tested for SARS-CoV-2 IgG antibody using the Abbott SARS-CoV-2 IgG assay. Participants also answered a questionnaire capturing data on demographics, history of COVID-19 symptoms, occupation, infection prevention and control measures. Overall, 95 of 1743 (5.5%) participants tested positive for SARS-CoV-2 IgG. Of these, 1.8% of the participants had mild or no COVID-19 symptoms and did not require a diagnostic test. Seropositivity was not associated with gender, occupation, hand hygiene and personal protective equipment (PPE) practices amongst HCWs. However, lack of physical distancing among health care workers in work areas and break room was associated with seropositivity (p = 0.05, p = 0.003, respectively). The majority of the HCWs are negative for SARS-CoV-2 IgG. This data highlights the need to promote infection prevention measures, and the importance of distance amongst co-workers to help mitigate infection rates.

Background Longitudinal serology studies can assist in analyzing kinetics of antibodies to the SARS-CoV-2 virus, helping to inform public health decision-making. Our study aims to characterize circulating antibody trends over 18 months in vaccinated participants with and without evidence of COVID-19 infection. Methods A cohort of healthcare workers employed at Boston Medical Center were followed, collecting serum samples and survey data over six timepoints from July 2020 through December 2021 (n = 527). History of SARS-CoV-2 infection, vaccination and booster status were confirmed, where possible, using electronic medical records. Serum was assessed for the qualitative detection of anti-N IgG and the semi-quantitative detection of anti-S IgG antibody levels. Piecewise regression models were utilized to characterize the antibody kinetics overtime. Results Anti-S IgG titers remained above the positivity threshold following infection and/or vaccination throughout the 18-month follow-up. Among participants with no evidence of COVID-19 infection, titers declined significantly faster in the initial 90 days post-full vaccination (β=-0.056) from December 2020 to March 2021 compared to the decline observed following booster dose uptake (β=-0.023) (p < 0.001). Additionally, COVID-19 infection prior to vaccination significantly attenuated the decline of anti-S IgG when compared to the infection-naïve participants following vaccine uptake (p < 0.001). Lastly, fewer boosted participants contracted Omicron (12.7%) than fully vaccinated (17.6%). Among the Omicron-positive participants, anti-S IgG titers were lower, but not significantly, than those who did not test positive when comparing by vaccination status. Conclusions These findings provide novel 18-month kinetics of anti-S IgG antibodies and further highlight the durability of hybrid immunity, underlining the strong humoral response stimulated by combined infection and vaccination.

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Background Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-associated mortality in women. In particular, triple-negative BC (TNBC) has the highest rate of mortality due in large part to the lack of targeted treatment options for this subtype. Thus, there is an urgent need to identify new molecular targets for TNBC treatment. RALA and RALB are small GTPases implicated in growth and metastasis of a variety of cancers, although little is known of their roles in BC. Methods The necessity of RALA and RALB for TNBC tumor growth and metastasis were evaluated in vivo using orthotopic and tail-vein models. In vitro, 2D and 3D cell culture methods were used to evaluate the contributions of RALA and RALB during TNBC cell migration, invasion, and viability. The association between TNBC patient outcome and RALA and RALB expression was examined using publicly available gene expression data and patient tissue microarrays. Finally, small molecule inhibition of RALA and RALB was evaluated as a potential treatment strategy for TNBC in cell line and patient-derived xenograft (PDX) models. Results Knockout or depletion of RALA inhibited orthotopic primary tumor growth, spontaneous metastasis, and experimental metastasis of TNBC cells in vivo. Conversely, knockout of RALB increased TNBC growth and metastasis. In vitro, RALA and RALB had antagonistic effects on TNBC migration, invasion, and viability with RALA generally supporting and RALB opposing these processes. In BC patient populations, elevated RALA but not RALB expression is significantly associated with poor outcome across all BC subtypes and specifically within TNBC patient cohorts. Immunohistochemical staining for RALA in patient cohorts confirmed the prognostic significance of RALA within the general BC population and the TNBC population specifically. BQU57, a small molecule inhibitor of RALA and RALB, decreased TNBC cell line viability, sensitized cells to paclitaxel in vitro and decreased tumor growth and metastasis in TNBC cell line and PDX models in vivo. Conclusions Together, these data demonstrate important but paradoxical roles for RALA and RALB in the pathogenesis of TNBC and advocate further investigation of RALA as a target for the precise treatment of metastatic TNBC.

Background The United States has been facing a worsening opioid epidemic over the past two decades. The veteran population represents a large and vulnerable group with a higher burden of mental health comorbidities. The purpose of this study was to analyze the impact of lumbar spine surgery on postoperative opioid usage in the United States veteran population. Methods A retrospective cohort study was conducted using the Veterans Affairs Informatics and Computing Infrastructure database. Patients who underwent lumbar spine surgery were stratified into three groups by their preoperative opioid claims within 365 days of surgery. Postoperative cumulative morphine milligram equivalents (MME) were tracked for each group and the paired Wilcoxon signed rank test was used to compare cumulative preoperative MME (days −365–0) to cumulative postoperative MME (days 91–455). Results At one year, 30.6% of patients in the high preoperative opioid group and 73.1% of patients in the low preoperative opioid group were no longer using opioids. In the opioid naive cohort, 10.0% of patients were still using opioids at one year. Among all patients, median cumulative postoperative MME was significantly less than median cumulative preoperative MME (P<0.001). High preoperative opioid usage of more than 3 claims was most significantly associated with continued postoperative opioid usage (odds ratio 12.55, P<0.001). From 2010 to 2020 the proportion of patients with preoperative opioid claims decreased (58.8% to 34.8%). Conclusions In the veteran population, lumbar spine surgery was effective in getting 50% of patients who were on opioids preoperatively to discontinue opioids postoperatively. Even minimal exposure to opioids preoperatively resulted in a 2.69-time increase in risk of being on opioids at one year versus opioid naive patients. This study affirms that despite being a high-risk population, the veteran population has a similar response to lumbar spine surgery as the general population in regards to opioid dependence.