Impact of triple intrathecal prophylaxis in acute lymphoblastic leukemia adults receiving HyperCVAD: A COVID-19 practice change.

Treatment of acute lymphoblastic leukemia (ALL) requires both systemically and locally directed therapies to prevent central nervous system (CNS) recurrence. In response to restrictions brought on by the COVID-19 pandemic, our institution adopted triple intrathecal (IT) chemotherapy for CNS prophylaxis during HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). We retrospectively reviewed records of newly diagnosed adult all patients who were consecutively treated with HyperCVAD between January 2011 and July 2022. Outcomes of patients who received triple IT chemotherapy and standard of care (SOC) CNS prophylaxis were compared. The primary endpoint was CNS relapse-free survival (RFS) while secondary endpoints included cumulative incidence of relapse, overall survival, number of outpatient, and total ITs per patient, and CNS treatment-related toxicities. A total of 37 patients including 21 in the triple IT and 16 in the SOC cohorts were evaluated. There were no differences between the triple IT and SOC cohorts with respect to CNS-RFS (89.6% vs. 80.4%; HR, 1.55; 95% CI, 0.45-5.39; p = .49), cumulative incidence of relapse (8.9% vs. 19.6%; HR, 1.14; 95% CI, 0.3-5.3; p = .87), and overall survival (89.6% vs. 85.7%; HR, 0.91; 95% CI, 0.20-4.21; p = .90) at 2-years. Significantly fewer IT doses were administered in the triple IT cohort (p = .011) and the number of additional outpatient appointments to administer IT chemotherapy were markedly reduced as 98.6% of IT doses were administered during scheduled admissions compared to 76.8% (p < .001). The adoption of triple IT chemotherapy did not increase CNS treatment-related toxicities but rather, the inverse was observed. Triple IT chemotherapy during HyperCVAD represents a feasible alternative to SOC CNS prophylaxis, especially during times of resource restriction and when minimization of patient exposures is desired.

Viral infectivity in pediatric SARS-CoV-2 clinical samples does not vary by age

At the start of the SARS-CoV-2 pandemic, there was much uncertainty about the role of children in infection and transmission dynamics. Through the course of the pandemic, it became clear that children were susceptible to SARS-CoV-2 infection, however they were experiencing a notable lack of severe disease outcomes as compared to the adult population. This trend held true with the emergence of new SARS-CoV-2 variants, even in pediatric populations that were ineligible to be vaccinated. The difference in disease outcomes has prompted questions about the virologic features of SARS-CoV-2 infection in this population. In order to determine if there was any difference in the infectivity of the virus produced by children infected with COVID-19, we compared viral RNA levels (clinical RT-qPCR CTs) and infectious virus titers from 144 SARS-CoV-2 positive clinical samples collected from children ages 0 to 18 years old. We found that age had no impact on the infectiousness of SARS-CoV-2 within our cohort, with children of all ages able to produce high levels of infectious virus.

Viral infectivity in pediatric SARS-CoV-2 clinical samples does not vary by age

At the start of the SARS-CoV-2 pandemic, there was much uncertainty about the role of children in infection and transmission dynamics. Through the course of the pandemic, it became clear that children were susceptible to SARS-CoV-2 infection, however they were experiencing a notable lack of severe disease outcomes as compared to the adult population. This trend held true with the emergence of new SARS-CoV-2 variants, even in pediatric populations that were ineligible to be vaccinated. The difference in disease outcomes has prompted questions about the virologic features of SARS-CoV-2 infection in this population. In order to determine if there was any difference in the infectivity of the virus produced by children infected with COVID-19, we compared viral RNA levels (clinical RT-qPCR CTs) and infectious virus titers from 144 SARS-CoV-2 positive clinical samples collected from children ages 0 to 18 years old. We found that age had no impact on the infectiousness of SARS-CoV-2 within our cohort, with children of all ages able to produce high levels of infectious virus.

Viral infectivity in pediatric SARS-CoV-2 clinical samples does not vary by age

At the start of the SARS-CoV-2 pandemic, there was much uncertainty about the role of children in infection and transmission dynamics. Through the course of the pandemic, it became clear that children were susceptible to SARS-CoV-2 infection, however they were experiencing a notable lack of severe disease outcomes as compared to the adult population. This trend held true with the emergence of new SARS-CoV-2 variants, even in pediatric populations that were ineligible to be vaccinated. The difference in disease outcomes has prompted questions about the virologic features of SARS-CoV-2 infection in this population. In order to determine if there was any difference in the infectivity of the virus produced by children infected with COVID-19, we compared viral RNA levels (clinical RT-qPCR CTs) and infectious virus titers from 144 SARS-CoV-2 positive clinical samples collected from children ages 0 to 18 years old. We found that age had no impact on the infectiousness of SARS-CoV-2 within our cohort, with children of all ages able to produce high levels of infectious virus.

Association of Symptoms After COVID-19 Vaccination With Anti-SARS-CoV-2 Antibody Response in the Framingham Heart Study.

This cohort study examines the association of self-reported postvaccination symptoms with anti­SARS-CoV-2 antibody response among Framingham Heart Study participants contributing to the Collaborative Cohort of Cohorts for COVID-19 Research study.

Establishment of a Captive Cave Nectar Bat (Eonycteris spelaea) Breeding Colony in Singapore.

Bats are known natural reservoirs of several highly pathogenic zoonotic viruses, including Hendra virus, Nipah virus, rabies virus, SARS-like coronaviruses, and suspected ancestral reservoirs of SARS-CoV-2 responsible for the ongoing COVID-19 pandemic. The capacity to survive infections of highly pathogenic agents without severe disease, together with many other unique features, makes bats an ideal animal model for studying the regulation of infection, cancer, and longevity, which is likely to translate into human health outcomes. A key factor that limits bat research is lack of breeding bat colonies. To address this need, a captive bat colony was established in Singapore from 19 wild-caught local cave nectar bats. The bats were screened for specific pathogens before the start of captive breeding. Custom-made cages and an optimized diet inclusive of Wombaroo dietary formula, liquid diet, and supplement of fruits enabled the bats to breed prolifically in our facility. Cages are washed daily and disinfected once every fortnight. Bats are observed daily to detect any sick bat or abnormal behavior. In addition, bats undergo a thorough health check once every 3 to 4 mo to check on their overall wellbeing, perform sampling, and document any potential pregnancy. The current colony houses over 80 bats that are successfully breeding, providing a valuable resource for research in Singapore and overseas.

COVID-19 Vaccination Hesitancy among Healthcare Workers-A Review.

The COVID-19 pandemic and its associated vaccine have highlighted vaccine hesitancy among healthcare workers (HCWs). Vaccine hesitancy among this group existed prior to the pandemic and particularly centered around influenza vaccination. Being a physician, having more advanced education, and previous vaccination habits are frequently associated with vaccine acceptance. The relationship between age and caring for patients on COVID-19 vaccination is unclear, with studies providing opposing results. Reasons for hesitancy include concerns about safety and efficacy, mistrust of government and institutions, waiting for more data, and feeling that personal rights are being infringed upon. Many of these reasons reflect previous attitudes about influenza vaccination as well as political beliefs and views of personal autonomy. Finally, several interventions to encourage vaccination have been studied, including education programs and non-monetary incentives with the most effective studies using a combination of methods.

PLACES: Local Data for Better Health.

Local-level data on the health of populations are important to inform and drive effective and efficient actions to improve health, but such data are often expensive to collect and thus rare. Population Level Analysis and Community EStimates (PLACES) (www.cdc.gov/places/), a collaboration between the Centers for Disease Control and Prevention (CDC), the Robert Wood Johnson Foundation, and the CDC Foundation, provides model-based estimates for 29 measures among all counties and most incorporated and census-designated places, census tracts, and ZIP Code tabulation areas across the US. PLACES allows local health departments and others to better understand the burden and geographic distribution of chronic disease-related outcomes in their areas regardless of population size and urban-rural status and assists them in planning public health interventions. Online resources allow users to visually explore health estimates geographically, compare estimates, and download data for further use and exploration. By understanding the PLACES overall approach and using the easy-to-use PLACES applications, practitioners, policy makers, and others can enhance their efforts to improve public health, including informing prevention activities, programs, and policies; identifying priority health risk behaviors for action; prioritizing investments to areas with the biggest gaps or inequities; and establishing key health objectives to achieve community health and health equity.

Safety of lung cancer surgery during COVID-19 in a pandemic epicenter.

BACKGROUND: The influence of SARS-CoV-2 on surgery for non-small cell lung cancer needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. OBJECTIVE: This study reports on the 90-day rate of infection as well as the morbidity and mortality of lung surgery for cancer in a tertiary care hospital located in a pandemic epicenter. METHODS: We conducted a retrospective review of a prospective database to identify consecutive patients who underwent lung cancer resection before (January 1, 2020-March 10, 2020, group 1; 57 patients) and during the COVID-19 pandemic (March 11, 2020-June 10, 2020, group 2; 41 patients). The primary end point was the occurrence of SARS-CoV-2 infection during the first 90-days after surgery. The secondary outcome measure was 90-day perioperative morbidity and mortality. RESULTS: Patient characteristics were not significantly different between the groups. Ninety-day COVID-19 infection rates was 7.3% (3 out of 41) for patients undergoing an operation during the pandemic and 3.5% (2 out of 57) in patients operated on immediately before the pandemic. All patients tested positive 10 to 62 days after the index surgical procedure following hospital discharge. Four COVID-19-positive patients were symptomatic and 4 out of 5 patients required hospitalization, were men, previous or current smokers with hyperlipidemia, and underwent a sublobar resection. Univariate analysis did not identify any differences in postoperative complications before or during the COVID-19 pandemic. Ninety-day mortality was 5% (2 out of 41) for lung cancer surgery performed during the pandemic, with all deaths occurring due to COVID-19, compared with 0% (0 out of 57) mortality in patients who underwent an operation before the pandemic. CONCLUSIONS: During the COVID-19 pandemic, COVID-19 infections occurred in 7.3% of patients who underwent surgery for non-small cell lung cancer. In this series all infections occurred after hospital discharge. Our results suggest that COVID-19 infections occurring within 90 days of surgery portend a 40% mortality, warranting close postoperative surveillance.

SARS CoV-2 seroprevalence in a US school district during COVID-19.

Reduced symptomatology and access to testing in children have led to underestimates of paediatric COVID-19 prevalence and raised concerns about school safety. To explore COVID-19 prevalence and risk factors in school settings, we conducted a SARS-CoV-2 serosurvey in a Vermont, USA school district in December 2020. Among 336 students (63%) and 196 teachers/staff (37%), adjusted seroprevalence was 4.7% (95% CI 2.9 to 7.2) and was lowest in preK-5 students (4-10 Years). Seroprevalence was 10-fold higher than corresponding state PCR data but was low overall with no evidence of onward transmissions. These results further support feasibility of in-person learning during COVID-19 with appropriate mitigation measures.

Hypophosphatemia is an independent risk factor for AKI among hospitalized patients with COVID-19 infection.

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.

Differentiating severe and non-severe lower respiratory tract illness in patients hospitalized with influenza: Development of the Influenza Disease Evaluation and Assessment of Severity (IDEAS) scale.

BACKGROUND: Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury. METHODS: We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010-2013 seasons. RESULTS: We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2-8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation <93% (47.6%) and respiratory rate >24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or <36.0°C (7.1% vs 27.1%), respiratory rate >24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation <90% (14.3% vs 31.4%), white blood cell count >15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%). CONCLUSION: We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.

Takotsubo syndrome after receiving the COVID-19 vaccine.

The coronavirus disease (COVID)-19 pandemic has affected millions worldwide with prevention efforts culminating in the development of a vaccine. An mRNA vaccine, developed by Moderna (Cambridge, MA, USA), mounts an immunologic response leading to antibody neutralization. Commonly reported vaccine side effects include myalgia, fever, and chills, with low reported rates of cardiovascular events. This case demonstrates the development of takotsubo syndrome (TTS) after administration of the COVID-19 vaccine. A 73-year-old woman with recently diagnosed myocardial infarction with no obstructive coronary atherosclerosis (MINOCA) presented with typical chest pain starting less than a day after receiving the Moderna vaccine. She had troponin elevations and new ST-segment abnormalities. Transthoracic echocardiogram (TTE) findings were consistent with mid-ventricular TTS. Treatment included diuretics, beta-blockers, and angiotensin receptor blockers. Prior to discharge, repeat imaging showed improvement in systolic function. This case presents a post-menopausal woman with a recent diagnosis of MINOCA who developed TTS shortly after receiving the COVID-19 vaccine. Risk factors including sex, age, MINOCA, anxiety about the vaccine, and possibly the vaccine itself may have all contributed to the TTS presentation. TTS may occur after COVID-19 vaccination, and appreciation of this potential rare association is important for evaluating vaccine safety and optimizing patient outcomes. .

Racial and Ethnic Disparities in Preoperative Surgical Wait Time and Renal Cell Carcinoma Tumor Characteristics.

Racial/ethnic minority groups have a disproportionate burden of kidney cancer. The objective of this study was to assess if race/ethnicity was associated with a longer surgical wait time (SWT) and upstaging in the pre-COVID-19 pandemic time with a special focus on Hispanic Americans (HAs) and American Indian/Alaska Natives (AIs/ANs). Medical records of renal cell carcinoma (RCC) patients who underwent nephrectomy between 2010 and 2020 were retrospectively reviewed (n = 489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination to date of nephrectomy. Out of a total of 363 patients included, 34.2% were HAs and 8.3% were AIs/ANs. While 49.2% of HA patients experienced a longer SWT (≥90 days), 36.1% of Non-Hispanic White (NHW) patients experienced a longer SWT. Longer SWT had no statistically significant impact on tumor characteristics. Patients with public insurance coverage had increased odds of longer SWT (OR 2.89, 95% CI: 1.53-5.45). Public insurance coverage represented 66.1% HA and 70.0% AIs/ANs compared to 56.7% in NHWs. Compared to NHWs, HAs had higher odds for longer SWT in patients with early-stage RCC (OR, 2.38; 95% CI: 1.25-4.53). HAs (OR 2.24, 95% CI: 1.07-4.66) and AIs/ANs (OR 3.79, 95% CI: 1.32-10.88) had greater odds of upstaging compared to NHWs. While a delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high-risk populations, such as HAs who have a prolonged SWT or choose active surveillance.

Modeling the impact of school reopening on SARS-CoV-2 transmission using contact structure data from Shanghai.

BACKGROUND: Mathematical modeling studies have suggested that pre-emptive school closures alone have little overall impact on SARS-CoV-2 transmission, but reopening schools in the background of community contact reduction presents a unique scenario that has not been fully assessed. METHODS: We adapted a previously published model using contact information from Shanghai to model school reopening under various conditions. We investigated different strategies by combining the contact patterns observed between different age groups during both baseline and "lockdown" periods. We also tested the robustness of our strategy to the assumption of lower susceptibility to infection in children under age 15 years. RESULTS: We find that reopening schools for all children would maintain a post-intervention R0 < 1 up to a baseline R0 of approximately 3.3 provided that daily contacts among children 10-19 years are reduced to 33% of baseline. This finding was robust to various estimates of susceptibility to infection in children relative to adults (up to 50%) and to estimates of various levels of concomitant reopening in the rest of the community (up to 40%). However, full school reopening without any degree of contact reduction in the school setting returned R0 virtually back to baseline, highlighting the importance of mitigation measures. CONCLUSIONS: These results, based on contact structure data from Shanghai, suggest that schools can reopen with proper precautions during conditions of extreme contact reduction and during conditions of reasonable levels of reopening in the rest of the community.

Lung Cancer Stage Shift as a Result of COVID-19 Lockdowns in New York City, a Brief Report.

INTRODUCTION: The COVID-19 pandemic reached New York City in early March 2020 resulting in an 11-week lockdown period to mitigate further spread. It has been well documented that cancer care was drastically affected as a result. Given New York City's early involvement, we attempted to identify any stage shift that may have occurred in the diagnoses of non-small cell lung cancer (NSCLC) at our institution as a result of these lockdowns. PATIENTS AND METHODS: We conducted a retrospective review of a prospective database of lung cancer patients at our institution from July 1, 2019 until March 31, 2021. Patients were grouped by calendar year quarter in which they received care. Basic demographics and clinical staging were compared across quarters. RESULTS: Five hundred and fifty four patients were identified that underwent treatment during the time period of interest. During the lockdown period, there was a 50% reduction in the mean number of patients seen (15 ± 3 vs. 28 ± 7, P = .004). In the quarter following easing of restrictions, there was a significant trend towards earlier stage (cStage I/II) disease. In comparison to quarters preceding the pandemic lockdown, there was a significant increase in the proportion of patients with Stage IV disease in the quarters following phased reopening (P = .026). CONCLUSION: After a transient but significant increase in Stage I/II disease with easing of restrictions there was a significant increase in patients with Stage IV disease. Extended longitudinal studies must be conducted to determine whether COVID-19 lockdowns will lead to further increases in the proportion of patients with advanced NSCLC.

Restricted human activities shift the foraging strategies of feral pigeons (Columba livia) and three other commensal bird species

Invasive species are a growing concern with increasing global connectivity. Feral pigeons (Columba livia) are widespread and invasive, thus their effective control is of keen international interest. The COVID-19 pandemic has offered an unprecedented opportunity to investigate the impact of a nation-wide Circuit Breaker (restricted human activities) in Singapore on first, the abundance of the feral pigeons and three urban commensals—the Javan myna (Acridotheres javanicus), common myna (A. tristis), and house crow (Corvus splendens) in different food source types;and second, the activity budgets of feral pigeons. A significant and progressive decline in feral pigeon abundance was observed in open food centres and feeding hotspots after the Circuit Breaker was implemented. While the house crow and common myna were less affected, the Javan myna abundance increased moderately at refuse collection centres during the Circuit Breaker and decreased significantly in green spaces after the Circuit Breaker. Changes in food abundance could also predict changes in feral pigeon abundance and its effect was greatest in feeding hotspots. A greater proportion of feral pigeons was observed foraging and moving with a smaller proportion seen resting with probable consequences on their reproductive capacity. Our study also cautions against drawing inferences on biological responses due to similar social restrictions without careful consideration of other ecological factors, like average flock size and time of the day, which also affected the proportion of pigeons foraging on natural versus anthropogenic food. In summary, our results advocate a food limitation approach to control the feral pigeon populations.