Acceptability of Telemedicine in a Geriatric Outpatient Practice During the COVID-19 Pandemic.

Background: Telemedicine utilization has increased dramatically during the COVID pandemic. Few studies have evaluated the use and acceptability of telemedicine in older populations. This study examined the use and acceptability of telemedicine with older adults in an urban, geriatric practice. Methods: An anonymous survey was sent to patients seen at an urban, geriatric practice using MyChart in EPIC in March 2021. This population of patients is 55 years and older, 50% Black, 40% white, 3% Latino, 3% Asian, and 4% other. This panel is comprised of 71% Medicare, 23% non-Medicare/non-Medicaid, and 6% Medicaid. The total panel of patients includes ∼1,400 patients. The percent of patients on MyChart at the time of the survey was 78%. Thus, about 1,092 patients received the survey. Results: Of the 1,092 patients who received the survey, 247 (22.6%) responded. Around 80.37% of respondents rated their overall experience with telemedicine as good or excellent. Theme areas emerged around the advantages and disadvantages of telemedicine. A majority (70.28%) of respondents rated themselves as Somewhat Confident to Very Confident in use of telemedicine without family/friend assistance. A majority (74.16%) of respondents stated they plan to use telemedicine again. Conclusions: This survey demonstrated the feasibility and acceptability of telemedicine in an urban, geriatric population. A limit to this study is that the survey was administered on-line, so that participants may be biased regarding use of online technology. However, this study showed that the vast majority of older adults were confident in using telemedicine as an alternative to in-person visits during the COVID pandemic and plan on using it again.

Investigating changes in longitudinal associations between declining bus ridership, bus service, and neighborhood characteristics

Amid the recent transit ridership decline, gaining an understanding of the factors affecting ridership becomes crucial for transit agencies to utilize limited resources effectively. I use generalized linear multilevel negative binomial models to investigate the longitudinal relationship and changes in the associations between neigh-borhood-level bus ridership and a series of socio-economic and bus service factors in Philadelphia between 2014 and 2018. Data come from passenger boarding at bus stops in Philadelphia. Results show that the associations between bus ridership, population and the number of jobs, and the percent of zero-car households are positive, but weakened over time. The associations between ridership and bus service supply are inelastic. The findings have implications on transit agencies' resource allocation and service adjustments as they recover from the ridership and revenue losses during the COVID-19 pandemic while facing competition from new travel options such as Uber and Lyft.

Post-Transplantation Cyclophosphamide for the Prevention of Graft-Versus-Host Disease Should Not Limit Transplantation for Acute Lymphoblastic Leukemia in People with Trisomy 21

Introduction: Use of hematopoietic cell transplantation (HCT) in patients with trisomy 21 (+21) is infrequent given concerns about increased toxicity with cytotoxic chemotherapy.1 Due to increasing evidence of benefit from post-HCT cyclophosphamide (PTCy) for graft-vs.-host disease (GVHD) prophylaxis and lack of prior descriptions in patients with +21,2-4 we report on 2 patients with +21 and acute lymphoblastic leukemia (ALL) who underwent HCT with PTCy. Method(s): Retrospective data were collected from 2 patients with ALL and +21 who underwent allogeneic HCT with PTCybased GVHD prophylaxis from 2019 to 2021. Data collected included age, disease risk, HCT-CI, GVHD incidence, and survival. Result(s): Patient 1 is a 22-year-old male and patient 2 a 25-year-old female. Both had Ph-negative, B-cell ALL. Patient 1 had ETV6/RUNX1 rearrangement, del 12p, gain of X, and he had recurrence of measurable residual disease (MRD) after initial MRD-negative CR with two lines of therapy pre-HCT. Patient 2 had normal cytogenetics and relapsed disease with 4 prior lines of therapy. Both achieved MRD-negativity pre-HCT. Both received fludarabine and melphalan conditioning, and patient 1 also received thiotepa 2.5 mg/kg. PTCy was given on days +3 and 4 at 50 mg/kg with sirolimus and tacrolimus for GVHD prophylaxis. Patient 1 had a haploidentical donor and received one dose of rabbit ATG (1 mg/kg) on day +5. Patient 2 had a matched unrelated donor. There was no significant delay in engraftment of ANC (day 16-19) or platelets (day 15-16). Patient 2 developed acute GVHD at day 30 (stage I skin, stage II GI) that resolved with steroids which were tapered off by day 96 without recurrence. Sirolimus stopped at day 79 (pt 1) and 103 (pt 2) and tacrolimus was stopped at day 274 (pt 1) and 469 (pt 2). Patient 1 developed a sirolimus-induced pericardial effusion at day 84 which did not recur after sirolimus discontinuation. Patient 2 developed moyamoya 8 months post-HCT during tacrolimus taper without other GVHD symptoms. Response to steroids was noted, so tacrolimus was restarted for residual neurological deficit. Neither patient developed chronic GVHD or left ventricular ejection fraction decline, and neither patient had disease relapse at follow-up of 30 and 16 months respectively. Patient 2 developed COVID pneumonia 16 months post-HCT and died while in CR. Patient 1 remains alive, in CR, and off immunosuppression nearly 3 years post HCT. Conclusion(s): Allogeneic HCT with PTCy at standard doses did not appear prohibitively toxic in patients with +21 when administered after reduced-intensity conditioning. In this case series, GVHD rates seemed consistent with larger series in patients without +21. Moyamoya development is associated with autoimmunity in patients with +21 and hence may have been GVHD-related5. Trisomy 21 should not be a barrier to patients otherwise eligible for HCT, even with PTCy prophylaxis.Copyright © 2023 American Society for Transplantation and Cellular Therapy

De‐prosecution and death: A reply to an imprecise and ideological critique

In an original article, I analyzed a potential causal link between the policy of de‐prosecution in Philadelphia and an increase in homicides. Utilizing the traditional synthetic control method with extensive descriptive data and a donor pool of the other 99 largest cities in the United States, the results demonstrated a statistically significant increase of over 74 homicides per year in Philadelphia during 2015‐19 associated with de‐prosecution (p<.05). A reaction essay addressing the original article on de‐prosecution has been submitted. In this reply, I correct inaccuracies in the reaction essay, explain the validity of methodological choices, discuss the reaction's misunderstanding of certain quantitative issues, and expose the ideological purposes of the reaction. In addition, I have included updated parallel research addressing the issue of de‐prosecution and examine the theoretical impact of the Covid‐19 pandemic on the interaction between de‐prosecution and homicides.

Outcomes of SARS-CoV-2 infection in Ph-neg chronic myeloproliferative neoplasms: results from the EPICOVIDEHA registry.

Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19-197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58-77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357-3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363-3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363-3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary: EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease.The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN.To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020.The database provided clinical data of 398 patients with MPN incurring COVID-19:Patients were mostly elderly (median age was 69 years);Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN;Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19.Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted byOlder age;Comorbidities;Exposure to immunosuppressive therapies.Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold byOlder age;Comorbidities;Exposure to immunosuppressive therapies before the infection.In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.

SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021.

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

Asciminib (Scemblix): A third-line treatment option for chronic myeloid leukemia in chronic phase with or without T315I mutation.

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To review the pharmacology, efficacy, safety, dosing and administration, and place in therapy of asciminib, an oral tyrosine kinase inhibitor (TKI) used as a third-line treatment option for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase. SUMMARY: CML is a rare cancer caused by a chromosomal translocation that forms a fusion of the BCR and ABL1 genes on chromosomes 22 and 9. Until recently, patients for whom first-line treatment options failed were treated with TKIs that bind to the adenosine triphosphate-binding site on BCR-ABL1. However, because of similar mechanisms of action, there continues to be an unmet need in patients for whom at least 2 TKIs have failed or those with a T315I mutation unable to tolerate ponatinib. In October 2021, the Food and Drug Administration approved asciminib (Scemblix), the first TKI specifically targeting the ABL1 myristoyl pocket (STAMP) via allosteric binding, as a third-line option for patients with chronic-phase (CP)-CML. Asciminib received accelerated approval due to meeting its primary endpoint at week 24, demonstrating a major molecular response rate of 25.5% for patients on asciminib compared to 13.2% for those receiving bosutinib. In addition, patients on asciminib achieved a higher rate of complete cytogenetic response at 40.8% compared to a rate of 24.2% for bosutinib. Clinicians prescribing asciminib should monitor for increased levels of pancreatic enzymes, hypertension, cardiovascular toxicity including ischemic and thromboembolic conditions, and decreased numbers of neutrophils and platelets, as these may require treatment interruption, dose reduction, or treatment discontinuation. CONCLUSION: Asciminib is a unique targeted TKI that provides clinicians with an additional third-line and beyond treatment option for adults with CP-CML regardless of mutation status as well as a second TKI treatment option for patients harboring a T315I mutation.

TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA DURING COVID-19

Background: During the coronavirus pandemic, the risk of severe COVID-19 and mortality are higher in certain groups, in particular in patients with oncohematological diseases. Acute lymphoblastic leukemia (ALL) is a special group of oncohematological diseases in which mortality in the era of COVID-19 has increased 2-3 times. Currently, there is no consensus on the treatment of ALL during coronavirus infection. Aims: To determine the basic principles and features of the management of patients with ALL during COVID-19. Methods: 46 patients with ALL and COVID-19 (men 52.2%, women 47.8%) aged 18-74 years (median-44.5) were treated at the Moscow City Clinical Hospital 52 on 01.04.20-01.11.21. B-ALL was 58.7% (27 patients), T-ALL - 34.8% (16 patients), biphenotypic - 4.3% (2 patients), not defined - 2.2% (1 patient), Ph-positive ALL - 17.4% (8 patients). The status of the disease of patients upon admission to the Hospital differed: debut of ALL - 20 patients (43.5%), remission - 16 patients (34.8%), relapse and refractory course - 10 patients (21.7%). All patients were treated COVID-19 in accordance with the current guidelines for the prevention, diagnosis and treatment of COVID- 19 (interleukin 6 inhibitor, anticoagulant and antibacterial therapy, glucocorticoids (GCs), human immunoglobulin (IG) against COVID-19). According to vital indications and with stabilization of the patient's condition, 18 patients (39.1%) received chemotherapy (CT). Results: There were no deaths in the group of patients with remission of ALL. In patients with the debut of ALL, mortality was 45% (9 patients), in relapse and refractory course - 50% (5 patients) (p=0.005). Mortality in the group who did not receive CT was 35.7%, and in the group who received CT - 22.2%. 6 patients with Ph-positive ALL (75.0%) continued therapy with tyrosine kinase inhibitors (TKI). According to the protocol for the treatment of ALL, full doses of GCs (100%) and anthracyclines (ATC) (100%) were used, lumbar punctures (LP) and intrathecal (IT) injections of CT (100%) were continued. Due to the high risk of thrombotic complications in COVID-19 and asparaginase therapy, anticoagulant therapy was performed (100%). Prevention of pneumocystis pneumonia (PCP) (89.1%), antifungal (37.0%) and antibacterial (87.0%) therapy were carried out in the treatment of COVID-19. With the persistence of COVID-19 and the absence of antibodies to COVID-19, 2 patients received repeated transfusion of human IG against COVID-19. Summary/Conclusion: During the COVID-19 pandemic, patients in remission of ALL coronavirus infection are treated and controlled. Treatment of COVID-19 in patients with ALL is carried out according to general protocols for the treatment of COVID-19, taking into account the peculiarities of nosology (agranulocytosis, high risk of PCP and fungal infection with long-term therapy of GCs, persistence of COVID-19). When the patient's condition is stabilized, the issue of CT should be decided individually in each case, taking into account all the risks of ALL and COVID-19. During CT, use full doses of GCs, ATC. In patients with mild and moderate COVID-19, continue LP and IT injections of CT, therapy with TKI.

Policing the largest drug market on the eastern seaboard: officer perspectives on enforcement and community safety

Purpose>The Kensington transit corridor runs between Huntingdon and Allegheny stations in the Kensington area of Philadelphia, Pennsylvania, and is one of the largest illicit drug areas in the country. The authors report qualitative findings from ride-alongs with transit police officers assigned to a vehicle patrol dedicated to reducing the response time to opioid overdoses in and around the transit system (trains and buses) in this large open-air drug market. This study's focus was on management and mitigation of the criminogenic harms associated with the illicit drug environment.Design/methodology/approach>For ten months, transit officers patrolled the Kensington transit corridor in a dedicated vehicle (callsign “Oscar One”). Oscar One operated during either an early (8 a.m. to 4 p.m.) or late (4 p.m. to midnight) shift, between September 2020 and June 2021. 269 shifts were randomly selected for Oscar One from 574 possible shifts. Researchers accompanied Oscar One for 51 observations (19%), 45 of which were completed by the authors. Semi-structured interviews occurred during these shifts, as well as ethnographic field observations.Findings>Four main themes emerged from the study. These centered on the role of law enforcement in a large drug market, the politics of enforcement within the city of Philadelphia, the policing world around risk and proactive engagement post–George Floyd, and the sense of police being overwhelmed on the front-line of community safety.Originality/value>Police officers have a community safety as well as a law enforcement mandate, and this study explores the community safety and harm mitigation role from their perspective. The article draws on their words, based on approximately 400 h of field observation.

Blinatumomab and inotuzumab ozogamicin for acute lymphoblastic leukaemia: data from the South East Scotland Cancer Network

Current therapy for adults with B-cell acute lymphoblastic leukaemia (B-ALL) remains suboptimal, despite good initial remission rates. Adults with relapsed or refractory B-ALL (R/R B-ALL) represent a challenge with historically poor outcome;the introduction of targeted agents has expanded options but there is no consensus management. Blinatumomab is a bispecific T-cell engager antibody construct against CD19 (Scottish Medicine consortium, SMC, approval February 2020);inotuzumab is a monoclonal anti-CD22 antibody conjugated to calicheamicin (SMC approval May 2018). Trial data have shown both agents improved remission rates and survival when compared with standard chemotherapy with manageable toxicity profiles, although adverse events including neurological toxicity and cytokine release syndrome (CRS) have been reported. We describe the experience of blinatumomab and inotuzumab in a BCSH level three unit from February 2017 to August 2021. Eleven patients-six male, five female, mean age 41.5 years (range 22-55) received a monoclonal antibody;blinatumomab ( n = 8) and inotuzumab ( n = 3). Ten had B-ALL and one had mixed lineage leukaemia (MLL). All patients were Philadelphia negative. Cytogenetic abnormalities were present in four cases-Inv(20), trisomy 21 (patient with Down syndrome), tetraploidy with isochromosome 17q and one with a complex karyotype. Further molecular information was available for nine cases, and all were negative for TCF3-PBX1 t(1;19), ETV6-RUNX1 t(12;21) and KMT2A rearrangements (including the case with MLL). Four patients received blinatumomab due to refractory BALL. Two (50%) went on to receive an allogeneic transplant in CR1 (one MRD negative and the other MRD below limit of quantification). Both patients were able to maintain a performance status of 0-1 pretransplant. One patient (25%) died due to SARS-COV-2 infection and the fourth patient's care was lost to follow-up. Four patients received blinatumomab due to relapsed BALL, two had undergone allogeneic transplant in CR1. Two patients (50%) died of progressive B-ALL. One patient is currently on UKALL 2011 regimen B maintenance B2 (comorbidities preclude allogeneic transplant), the other patient remains in molecular remission having failed lymphocyte collection for chimeric antigen (CAR) T-cell therapy. Three patients received inotuzumab for relapsed B-ALL. Two (66%) had a previous allogeneic transplant in CR1-one of whom went on to receive donor lymphocyte infusion (DLI) postinotuzumab while the other patient went on to have a second allogeneic transplant. The third patient relapsed on maintenance chemotherapy and has been referred for allogeneic transplant. Infective episodes occurred in 45% (all received blinatumomab) including one death from SARS-COV-2 pneumonitis. Following blinatumomab CRS and neurotoxicity (tonic-clonic seizures) occurred (both n = 1). No significant toxicities were observed in the three patients who received inotuzumab, although this likely reflects small patient numbers rather than a true difference between the two agents. Despite improved responses in R/R B-ALL with these therapies as single agents for the majority they do not offer cure. While toxicity was recorded it did not negatively impact PS. CAR T-cell therapy has demonstrated high initial remission rates in heavily treated B-ALL patients, including previous targeted therapy. Optimal sequencing of therapies remains to be defined alongside depth of response and duration of measurement.

A prospective phase 2 study testing high dose post-transplant cyclophosphamide as sole GHVD prophylaxis after matched allotransplant using baltimore-based reducedintensity conditioning regimens and PBSC as source of graft

Introduction: The use of high-dose post-transplant cyclophosphamide (PTCY) has revolutionized graft-versus-host disease (GVHD) prophylaxis and allowed to successfully reconsider haplotransplant in recent years. As this strategy significantly reduces the incidence of both acute and chronic GVHD, PTCY has been thereafter considered not only in matched settings but also as sole GVHD prophylaxis, at least when considering myeloablative allotransplant using matched sibling (MSD) or unrelated (MUD) donors and bone marrow as source of graft. Here, PTCY, as a sole GVHD prophylaxis, was tested in a reduced-intensity conditioning (RIC) setting, using peripheral blood stem cells (PBSC) as source of graft considering that this platform is currently broadly used worldwide in adults. Methods: This prospective monocentric phase 2 study was designed with the main objective to demonstrate the feasibility and safety of using only PTCY (without cyclosporine A nor mycophenolate mofetyl after transplant) in adults (18-70 years old) eligible for a RIC PBSC transplant with MSD or MUD. The Baltimore platform with 2 days of PTCY 50mg/kg/day on days 3 and 4 post infusion was considered as conditioning regimen, using fludarabine for lymphoid disease or clofarabine for myeloid disease. The primary objective was to appreciate the incidence of corticosteroid-resistant acute grade 3-4 GVHD (CR 3-4 GVHD) within 100 days post-transplant. According to statistical rules, patients have to be included in a step by step fashion (3, 3, 6, 15, 15 and 17 patients) for a total of 59 evaluable patients (meaning having received PTCY), in order to stop the protocol soon enough in case of excessive rate of deleterious severe acute GVHD (graded according to Mount Sinai International Consortium). Thus, the trial had to be stopped in case of documentation of > 2 CR 3-4 GVHD for the first 3 patients, >3 CR 3-4 GVHD for the first 6 patients, > 4 CR 3-4 GVHD for the first 12 patients, > 6 3-4 CR GVHD for the first 27 patients, > 8 CR 3-4 GVHD for the first 42 patients and finally as soon as > 9 CR 3-4 GVHD for the last included patients. All patients gave informed consent. The trial was registered at ClinicalTrials.gov Identifier: NCT03263767. Results: The results of the first 27 first patients (males n=17 and female n=10;median age: 59 years old (yo), range: 26-70) are reported here. They were included between February 2018 and November 2020. Diagnoses were AML (N=8), MDS (N=5), CMML (N=2), myelofibrosis (N=5), CML (N=1), DLBCL (N=1), T-cell lymphoma (N=1), Philadelphia positive B-ALL (N=1), CLL (N=1), lymphoblastic lymphoma (N=1) and mixed phenotype acute leukemia (N=1). Donors were MSD in 10 cases and MUD in 17. Only one primary graft failure was documented in a 61 yo MDS patient with active disease at transplant. He is however still alive in response after autologous reconstitution. With a median follow-up of 17.6 months (range: 10-42) for alive patients at the time of analysis (July 2021), 1-year and 2-year survivals were 80.9+7% and 74.7+9%, respectively, for both OS et DFS. GVHD-free/relapse-free survival (GRFS) at 1-year and 2-year was 58.7+9% and 52.2+10%, respectively. Three relapses (11%) and 6 deaths occurred. Deaths were due to acute GVHD in 4 patients (including 1 with sepsis and 1 with SARS-COVID 19 infection) and relapse in 2. Grade 2, 3 and 4 acute GVHD occurred in 11, 1 and 4 patients, respectively, for a total of 59% of grade 2-4 acute GVHD. CR 3-4 GVHD was observed in all of 5 patients with acute grade 3-4 GVHD and 4 died related to GVHD. Moderate/severe chronic GVHD occurred in 5/22 (22.7%) evaluable patients, including 4 still on immunosuppressive therapy at 40, 28, 25 and 16 months post-transplant. Overall non-relapse mortality (NRM) was 14.8% and related to acute GVHD. However, the number of cases conducting to stop the protocol was not reached. Conclusion: PTCY as a sole GVHD prophylaxis is here demonstrated as possible and relatively safe for adults receiving a matched PBSC Baltimore-based RIC allograft. The very good survivals reported he e may be related to a strong GVL effect associated with the high incidence of acute GVHD. However, because of this high incidence and the fact that NRM was related to GVHD after this first analysis, we have now made an amendment to test the addition to PTCY of one day of anti-thymoglobulin (ATG) 2.5 mg/kg on day-2 for the next 32 patients to be included. This second cohort receiving PTCY+ATG as a sole prophylaxis is ongoing.

Outcomes of Patients with Hematologic Malignancies and COVID-19: Perspective of a Large Hematology Center in Greece

The emergence of SARS-CoV-2, as of July 2021 has affected 469,042 individuals and accounted for 12,851 deaths nationally in Greece, according to WHO database. Mortality rate is higher in elderly patients (pts) and in pts with comorbidities, including malignancies. However, there is a growing interest on COVID-19 outcomes in pts with hematologic diseases. The aim of this study was to perform a systematic registration and analysis of the outcomes of pts with hematologic disease and COVID-19 in our center. The study is a single-center, retrospective study, conducted at a Hematology Department and HCT unit of a tertiary Hospital after approval from local Ethics Committee. We included pts with a hematologic disease and RT-PCR confirmed COVID-19 infection between October 2020 and July 2021. We reviewed hematological medical records to extract demographic and clinical data of COVID-19 infections. Most of the data have already been intergraded in ASH Research Collaborative Data Hub. Hematologic diseases were categorized to: Acute Myeloblastic Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Non-Hodgkin Lymphomas (NHL), Chronic Lymphocytic Leukemia (CLL), Hodgkin Lymphoma (HL), Multiple Myeloma (MM), Myelodysplastic Syndromes (MDS), Chronic Myeloid Leukemia (CML), Myeloproliferative Neoplasms (MPN, including all Philadelphia-negative MPN) and other hematologic conditions. We evaluated a total of 89 pts, 54% were male and 46% female, with a median age of 64.5 (20-86) and 59.5 (21-85) years respectively. 83% of pts were ≥40 years and 27% ≥70 years old. Most of them (92%) acquired infection outside a hospital setting. 13% of pts were asymptomatic and diagnosis was confirmed only with positive RT-PCR test. The most common represented malignancies were NHL 26%, CLL 20% and acute leukemias 13.5%, while 15% of pts underwent transplantation (HCT). Pts presented with moderate/severe COVID-19 were 55%, while 43% of hospitalized pts required Intensive Care Unit (ICU) admission. Overall, the death rate was 24%, while remarkably almost all pts required ICU support did not survive (mortality 94%). Higher mortality observed in patients with MDS (50%), MM (43%), CLL (39%), ALL (33%) and NHL (30%). Further analysis showed a positive correlation between mortality and male gender with 16 deaths out of 21 (p =.0245), as well as mortality and ICU admission (p <.001). A chi-square test of independence was performed to examine the relation between age and COVID-19 severity, without any statistically significant result [x 2 (2, N = 87) = 3.475, p =.176]. Whereas the only significant correlation between age and mortality was among age groups 18-39 and >70 years (p =.0146). Regarding treatment, pts were divided into two subgroups, 78% of them received anticancer therapy at least once in their lives, while 22% of them have never been on treatment, mainly pts with CLL and indolent NHL. 62% of the first subgroup manifested moderate/severe COVID-19 infection requiring hospitalization with 28% death rate, while the same rates in the 2 nd subgroup were 30% and 10% respectively. Although there was a significant correlation between the treatment status and the severity of COVID-19 infection (p =.020), the above was not translated in statistically higher death rate in the first subgroup (p =.14). There was also a correlation between HCT and COVID-19 severity in general (p =.005), with autologous HCT having statistically higher mortality than the allogeneic subgroup (p =.032). Α similar analysis in CLL and NHL groups showed no relation among treatment status, COVID-19 severity, and mortality (p values.638 and.115/.34 and.62 respectively). As anticipated in hematological pts, the immunocompromised nature of the underlying disease makes them extremely vulnerable to COVID-19 infection regardless of their treatment status, a fact that is also reflected in mortality despite ICU admission and support. In general, the severity of infection is correlated to anticancer therapy, while mortality to male sex, ICU admission and autologous HCT. Larger number of pts are necessary for further studies to better understand the parameters that impact the outcome of COVID-19 in hematological pts. Hematology departments should remain COVID-19 free zones, dedicated only to hematologic treatment and pts should strictly comply with social distancing. It remains to see if vaccines can play a key role to protect this special group of pts. [Formula presented] Disclosures: Anagnostopoulos: Abbvie: Other: clinical trials;Sanofi: Other: clinical trials;Ocopeptides: Other: clinical trials;GSK: Other: clinical trials;Incyte: Other: clinical trials;Takeda: Other: clinical trials;Amgen: Other: clinical trials;Janssen: Other: clinical trials;novartis: Other: clinical trials;Celgene: Other: clinical trials;Roche: Other: clinical trials;Astellas: Other: clinical trials.

Immunotherapy with GcMAF revisited - A critical overview of the research of Nobuto Yamamoto.

This overview describes the research of Nobutu Yamamoto (Philadelphia) concerning immunotherapy with GcMAF for patients with cancer and for patients infected with pathogenic envelope viruses. GcMAF (Group-specific component Macrophage-Activating Factor) is a mammalian protein with an incredible potency to directly activate macrophages. Since the late 1980s Yamamoto's investigations were published in numerous journals but in order to understand the details of his research, a minute survey of many of his patents was required. But even then, regrettably, a precise description of his experiments was sometimes lacking. This overview tries to summarize all of Yamamoto's research on GcMAF, as well as some selected more recent papers from other investigators, who tried to verify and/or reproduce Yamamoto's reports. In my opinion the most important result of the GcMAF research deserves widespread renewed attention: human GcMAF injections (100 ng per week, intramuscular or intravenous) can help to cure patients with a great variety of cancers as well as patients infected with pathogenic envelope viruses like the human immunodeficiency virus 1 (HIV-1), influenza, measles and rubella (and maybe also SARS-CoV-2). From Yamamoto's data it can be calculated that GcMAF is a near-stoichiometric activator of macrophages. Yamamoto monitored the progress of his immunotherapy via the serum level of an enzyme called nagalase (α-N-acetylgalactosaminidase activity at pH 6). I have extensively discussed the properties and potential catalytic site of this enzyme activity in an Appendix entitled: "Search for the potential active site of the latent α-N-acetylgalactosaminidase activity in the glycoproteins of some envelope viruses".

Crises and Contestations: The Promise and Peril of Designing a Green New Deal

It is clear that we are facing a tipping point in global politics, climate change and social justice. Much has been trumpeted under the banner of the 'Green New Deal'. Billy Fleming, the Wilks Family Director of the Ian L McHarg Center at the Weitzman School of Design, University of Pennsylvania, describes the history and various approaches encompassed within this ubiquitous epithet and how designers can get involved.

Fractionated Inotuzumab Ozogamicin Combined with Low-Intensity Chemotherapy Provides Very Good Outcome in Older Patients with Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: First Results from the EWALL-INO Study

On behalf of the GRAALL group, the Czech Republic ALL group, the Finland ALL group and the EWALL group. Introduction. Treatment of older patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains an unmet medical need. Inotuzumab ozogamicin (INO), an anti-CD22 antibody conjugated to calicheamicin, is approved for the treatment of relapsed/refractory BCP-ALL in adults, sinusoidal obstruction syndrome (SOS) being the major adverse event associated with INO. A previous first line study conducted by the MDACC in pts 60 years or older successfully used INO in combination with a lower intensity version of the hyper-CVAD (mini-hyper-CVD). Due to the occurrence of SOS, the total doses were fixed at 1.3 mg/m² for cycle 1 followed by 3 cycles at 1 mg/m² (Kantarjian H et al. Lancet Oncol, 2018). Here, we aimed to assess the activity and safety of fractionated INO at a reduced dosage in combination with low-intensity chemotherapy as frontline therapy for older pts with CD22+ Philadelphia chromosome-negative (Ph-neg) BCP-ALL. Methods. EWALL-INO is a single arm prospective phase 2 multicentric study conducted in European centers belonging to the EWALL group. Eligibility criteria were pts aged 55y or older, performance status ≤2, and newly diagnosed CD22+ (20% or more of positive blast cells) Ph-neg BCP-ALL without central nervous system involvement. After a prephase including 5 days (D) of dexamethasone (DEX) 10mg per D and a single intrathecal injection (IT), the induction regimen was begun and split in 2 parts. Induction part I (Induc1) consisted of one triple IT, vincristine (VCR) 2 mg (1 mg over 70y) D1 D8 D15 D22 and DEX 20 mg D1D2 D8D9 D15D16 D22D23 combined with 3 injections of INO (0.8 mg/m² D1, 0.5 mg/m² D8 and D15). Induction part II (Induc2) was offered to pts in CR or CRp (CR with platelets < 100 G/l) after Induc1 or as salvage therapy. Induc2 consisted of DEX 20mg D1D8, cyclophosphamide (CY) 300 mg/m² D1 to D3, one triple IT D2 and 2 injections of INO (0.5 mg/m² D1 and D8). Pts in CR/CRp were programmed to receive 6 blocks of consolidation (Ara-C 1.5g/m²/12h adapted to renal clearance D1D2 and DEX 10mg/12h D1D2, cycles 1 and 4;Methotrexate (MTX) 1.5 g/m² over 24h D1, VCR 1 or 2 mg D1, one triple IT D2 and 6-mercaptopurin (6-MP) D1 to D7, cycles 2 and 5;CY 500 mg/m² D1D2, VP16 75 mg/m² D1D2, one triple IT D2 and MTX 25 mg/m² D1, cycles 3 and 6) followed by a POMP maintenance (VCR, 6-MP, MTX, DEX) during 18 months. Allograft was allowed after at least 3 blocks of consolidation at the discretion of the investigators. The evaluable population was pts who received at least 1 dose of INO. Analyses were by modified intention to treat and performed JUN 28, 2021. All pts gave informed consent. The study is registered at ClinicalTrials.gov under the NCT number: NCT03249870. Results. Between DEC 29, 2017 and JUN 22, 2021, 115 pts (out of 130 planned pts) were enrolled including 6 pts with screen failure. The first 90 eligible pts (up to MAR 1, 2021) were considered for this analysis to obtain a minimum of 4 months follow-up. Median age was 69y (range 55-84) and median follow-up for alive pts was 1.18 years (range 0.3-3.5). At time of analysis, 90 and 88 pts had started induc1 and induc2, respectively. Treatment related mortality was 2.2% (2/90) and CR/CRp rate was 85.5% (77/90, 6 CRp) after induc1. Three cases relapsed between induc1 and induc2 and 5 pts were salvaged by induc2 allowing to a CR/CRp rate of 87.7% (79/90, 8 CRp) after induc2. One pts died from refractory disease during induc2. One, 2, 3 4 and 5 injections of INO were administered to 2 (2.2%), 2(2.2%), 11 (12.2%), 2 (2.2%) and 73 pts (81.1%) respectively. Only 6 pts were allografted. One-year OS was estimated to be 78.5% (95%CI 68-85.9) and median OS was not reached. One-year relapse free survival was 74.5% (95CI 63.5-82.6) (Figure 1). Grade 3-4 liver toxicity was observed in 8 pts (8.8%) during the study including 3 pts (3.3%) developing SOS, 2 related to INO during induc1 and one occurred after transplant. Twenty-nine pts died during the follow-up, 16 from relapses (overall incidence 18%) and 13 from adverse events (overall incidence 14.4%), including one COVID19 fatal infection during consolidation. Conclusion. Fractionated inotuzumab ozogamicin at reduced doses (0.8/0.5/0.5/0.5 mg/m²) combined with low-intensity chemotherapy is a very active and well tolerated frontline therapy for older patients with CD22+ Ph-neg BCP-ALL. [Formula presented] Disclosures: Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Huguet: Novartis: Other: Advisor;Jazz Pharmaceuticals: Other: Advisor;Celgene: Other: Advisor;BMS: Other: Advisor;Amgen: Other: Advisor;Pfizer: Other: Advisor. Raffoux: ABBVIE: Consultancy;PFIZER: Consultancy;CELGENE/BMS: Consultancy;ASTELLAS: Consultancy. Boissel: CELGENE: Honoraria;Servier: Consultancy, Honoraria;Incyte: Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Bristol-Myers Squibb: Honoraria, Research Funding;PFIZER: Consultancy, Honoraria;JAZZ Pharma: Honoraria, Research Funding;SANOFI: Honoraria. Dombret: Amgen: Honoraria, Research Funding;Incyte: Honoraria, Research Funding;Jazz Pharmaceuticals: Honoraria, Research Funding;Novartis: Research Funding;Pfizer: Honoraria, Research Funding;Servier: Research Funding;Abbvie: Honoraria;BMS-Celgene: Honoraria;Daiichi Sankyo: Honoraria. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. OffLabel Disclosure: Inotuzumab ozogamicin as first line therapy in newly diagnosed CD22+ Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia

Autoantibodies Against Type I IFNs in Patients with Ph-Negative Myeloproliferative Neoplasms

Background. The classic Ph-negative myeloproliferative neoplasms (MPN) are a group of clonal haematopoietic disorders, including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF), whose shared and diverse phenotypic signatures are caused by a dysregulated JAK/STAT signal transduction because of acquired somatic mutations. It has been demonstrated that autoimmune diseases and MPN can be associated (Kristinsson et al., Haematologica. 2010 Jul;95(7):1216-20.), suggesting a common background of immune dysregulation (Barosi, Curr Hematol Malig Rep. 2014 Dec;9(4):331-9). SARS-CoV-2 infection displays extreme inter-individual clinical variability, ranging from silent infection to lethal disease. It has been described that at least 10% of patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia have neutralizing autoantibodies (AAbs) against type I IFNs, that precede SARS-CoV-2 infection (Bastard et al., Science. 2020 Oct 23;370(6515):eabd4585). In this study we searched for AAbs against type I IFNs in a cohort of MPN patients to evaluate the prevalence of these AAbs in the MPN population and to check for clinical correlations, including severity of COVID-19. Methods. Plasma samples from consecutively referred MPN patients were prospectively collected between November 2020 and June 2021 and frozen at -30°C immediately after collection. Levels of AAbs against type I IFN subtypes including IFNs alpha, beta and omega were measured using the enzyme-linked immunosorbent assay (ELISA) and a neutralization assay, as previously reported (Bastard et al., Science. 2020 Oct 23;370(6515):eabd4585;Moreews et al., Sci Immunol. 2021 May 25;6(59):eabh1516). Results. We included a total of 219 MPN patients (101 ET, 76 PV, 36 MF and 6 MPN unclassificable). Neutralizing AAbs to type I IFNs were detected in 29 patients (13.2%, 95%CI: 9.1% - 18.5%). Comparing patients with and without AAbs we observed a significant difference in terms of distribution of MPN diagnosis (P = 0.029) and driver mutations (P = 0.019), while we did not observe a difference in terms of age, sex, and treatment (Table 1). Overall, 29 patients (13%) got SARS-CoV-2 infection and 8 of them (28%) required hospitalization due to severe COVID-19. AAbs against type I IFNs were detected in 4 of the 29 SARS-CoV-2 infected patients. A higher rate of hospitalization for severe COVID-19 was observed in patients with AAbs to type I IFNs (2 of 4 patients, 50%) compared to those without these AAbs (6 of 25 patients, 24%), although the difference did not reach a statistical significance (P = 0.300). Conclusions. In this study, we detected a prevalence of AAbs against type I IFNs which is much higher in our MPN cohort (13%) than in the general population (2-3%). We also found a correlation between the presence of AAbs to type I IFNs and both the hematological diagnosis and the driver mutation. Despite a comparable prevalence of SARS-CoV-2 infection between MPN patients with or without AAbs to type I IFNs, we observed a different rate of hospitalization due to severe COVID-19 which is almost twice in those with AAbs against type I IFNs compared to those without these AAbs. However, this difference did not reach a statistical significance, probably because of the low number of SARS-CoV-2 infection in the subgroup of patients with AAbs against type I IFNs. Thus, further studies to analyse the prevalence of AAbs against type I IFNs in patients with MPN, their association with other forms of auto-immunity and severe COVID-19 are warranted. [Formula presented] Disclosures: Arcaini: Gilead Sciences: Research Funding;Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy;Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses;Celgene: Speakers Bureau. Rumi: Novartis, Abbvie: Consultancy.

Acute and Post-Acute COVID-19 Severity and Mortality in Patients with Hematologic Malignancies: A Population-Based Registry Study

Introduction: The severity of acute clinical outcomes and mortality in hematologic malignancy (HM) patients infected by SARS-CoV-2 was exhaustively documented in the first weeks of the pandemic. A consistent increased mortality compared to non-cancer patients was observed across studies. In this study we aimed to estimate survival in COVID-19 HM patients by type of malignancy, to describe acute and post-acute clinical outcomes, and to compare outcomes in early and later pandemic periods. Methods: In this population-based registry study sponsored by the Madrid Society of Hematology (Asociación Madrileña de Hematología y Hemoterapia), we collected de-identified data on clinical characteristics, treatment and acute and post-acute outcomes in adult patients with hematologic malignancies and confirmed SARS-CoV-2 infection within the Madrid region of Spain. Our case series included all eligible patients admitted to 26 regional health service hospitals and 5 private healthcare centers between February 28, 2020 and February 18, 2021 with a coverage of 98% on a population of 6.6 million inhabitants. The study outcomes were all-cause mortality, severity of disease (WHO), oxygen support, ICU admission, and follow-up symptoms and signs and complications. Survival probabilities were estimated with the actuarial method and reported overall and stratified by type of malignancy and for two study periods (early cohort,-COVID-19 diagnosis from February 28 to 31 May, 2020, and later cohort, up to February 18, 2021). Results: Of the 1408 patients reported to the HEMATO-MADRID COVID-19 registry, 1166 were included in the present analyses;839 (72%) had a lymphoid malignancy, including 325 (28%) with non-Hodgkin lymphoma, 50 (4%) with Hodgkin lymphoma and 263 (23%) with multiple myeloma;and 327 (28%) had a myeloid malignancy, including 115 (10%) with myelodysplastic syndrome, 92 (8%) with acute myeloid leukemia (AML) and 87 (7%) with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. Overall COVID-19 clinical severity was classified as critical in 19% of patients, severe in 36%, moderate in 22%, and mild in 22%;10% were admitted to an ICU;8% were on mechanical ventilation and 19% on noninvasive ventilation. Mild disease increased between early and later period from 15% to 38% of patients;severe disease decreased from 42% to 24%, p<0.001. COVID-19 treatment with steroids increased from 38% to 59%, p<0.001. At follow-up, 22% reported persistent symptoms related to COVID-19 at 2 months, 16% at 4 months and 14% at 6 months. 381 of 1166 (33%) patients died. Overall 30-day survival was 68%;2 and 3-month overall survival probabilities were 56% and 53%, respectively. Survival was more favorable for patients with myeloproliferative neoplasms (82%, 69% and 65% at 30-days, 2 and 3 months, respectively) than for those with lymphoid malignancies (68%, 56% and 54%) or myelodysplastic syndrome/acute myeloid leukemia (61%, 51%, 46%), p=001. 285 (37%) patients died in the early period vs 96 (24%) in the later, p<0.001, but median (interquartile range) follow-up time was much higher in the early vs later, 45 (20-116) days vs. 26 (11-86), respectively. Overall survival was not different between periods, p=0.5 (hazard ratio [95%C], 0.93 [0.73-1.17]). In the later cohort, 30 and 60-day survival probabilities were 71% and 56% vs. 67% and 56% in the early cohort Conclusions. A population-based registry in Spain provided strong evidence that although COVID-19 severity decreased over year 1 of the pandemic, mortality remained high, and survival was stable over time in the group of patients with hematological malignancy infected by SARS-Coc-2. A relevant proportion of the infected patients (1 in 6) referred persistent symptoms attributable to COVID-19. The improved clinical management of severe COVID-19 in non-cancer patients that followed the dissemination of evidence-based recommendations did not translate in more favorable survival in patients with hematological malignancies. Research is needed to address the specific characteristics nd improve the clinical management of this vulnerable population. Disclosures: Martinez-Lopez: Novartis: Consultancy, Speakers Bureau;BMS: Consultancy, Research Funding, Speakers Bureau;Janssen: Consultancy, Speakers Bureau;Incyte: Consultancy, Research Funding, Speakers Bureau;Roche: Consultancy, Research Funding, Speakers Bureau;Astellas: Research Funding, Speakers Bureau. Jiménez-Yuste: Pfizer: Consultancy, Honoraria, Research Funding;Grifols: Consultancy, Honoraria, Research Funding;CSL Behring: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Bayer: Consultancy, Honoraria, Research Funding;NovoNordisk: Consultancy, Honoraria, Research Funding;BioMarin: Consultancy;Sobi: Consultancy, Honoraria, Research Funding;Octapharma: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding. Kwon: Gilead: Honoraria.

Dynamic Panel Data Modeling and Surveillance of COVID-19 in Metropolitan Areas in the United States: Longitudinal Trend Analysis.

BACKGROUND: The COVID-19 pandemic has had profound and differential impacts on metropolitan areas across the United States and around the world. Within the United States, metropolitan areas that were hit earliest with the pandemic and reacted with scientifically based health policy were able to contain the virus by late spring. For other areas that kept businesses open, the first wave in the United States hit in mid-summer. As the weather turns colder, universities resume classes, and people tire of lockdowns, a second wave is ascending in both metropolitan and rural areas. It becomes more obvious that additional SARS-CoV-2 surveillance is needed at the local level to track recent shifts in the pandemic, rates of increase, and persistence. OBJECTIVE: The goal of this study is to provide advanced surveillance metrics for COVID-19 transmission that account for speed, acceleration, jerk and persistence, and weekly shifts, to better understand and manage risk in metropolitan areas. Existing surveillance measures coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until, and after, an effective vaccine is developed. Here, we provide values for novel indicators to measure COVID-19 transmission at the metropolitan area level. METHODS: Using a longitudinal trend analysis study design, we extracted 260 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in the 25 largest US metropolitan areas as a function of the prior number of cases and weekly shift variables based on a dynamic panel data model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Minneapolis and Chicago have the greatest average number of daily new positive results per standardized 100,000 population (which we refer to as speed). Extreme behavior in Minneapolis showed an increase in speed from 17 to 30 (67%) in 1 week. The jerk and acceleration calculated for these areas also showed extreme behavior. The dynamic panel data model shows that Minneapolis, Chicago, and Detroit have the largest persistence effects, meaning that new cases pertaining to a specific week are statistically attributable to new cases from the prior week. CONCLUSIONS: Three of the metropolitan areas with historically early and harsh winters have the highest persistence effects out of the top 25 most populous metropolitan areas in the United States at the beginning of their cold weather season. With these persistence effects, and with indoor activities becoming more popular as the weather gets colder, stringent COVID-19 regulations will be more important than ever to flatten the second wave of the pandemic. As colder weather grips more of the nation, southern metropolitan areas may also see large spikes in the number of cases.

Universal testing for severe acute respiratory syndrome coronavirus 2 in 2 Philadelphia hospitals: carrier prevalence and symptom development over 2 weeks.

Background: The coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2 has challenged obstetrical care providers. Universal testing on labor and delivery units has been implemented by many hospitals to ensure patient and staff safety. Asymptomatic carrier rates are expected to vary based on geographic differences in disease prevalence, although differences within the same city have not been reported previously. In addition, clinical follow-up of women who had a negative result for severe acute respiratory syndrome coronavirus 2 during obstetrical hospitalization has not been included in any previous reports. Objective: This study aimed to describe the prevalence of positive severe acute respiratory syndrome coronavirus 2 test results among asymptomatic pregnant women at 2 Philadelphia obstetrical hospitals, characterize the clinical course of those who had a positive result, and report symptom development among all women tested in the 2 weeks after hospitalization. Study Design: This is an observational study of asymptomatic pregnant women who underwent severe acute respiratory syndrome coronavirus 2 testing at 2 academic health centers (Hospital of the University of Pennsylvania and Pennsylvania Hospital) in Philadelphia, Pennsylvania, between April 13, 2020, and April 26, 2020. All women tested were contacted via telephone for symptom follow-up at 1 and 2 weeks after discharge. Asymptomatic positive test rates are reported for the overall population and by hospital. The hospital and 2-week posthospital course are described for women who had a positive result for severe acute respiratory syndrome coronavirus 2. Posthospital symptom development among women who had a negative result for severe acute respiratory syndrome coronavirus 2 is also described. Results: A total of 318 asymptomatic women underwent severe acute respiratory syndrome coronavirus 2 testing during this 2-week period; 8 women had a positive result. The overall asymptomatic test positive rate was 2.5%. The rate at Hospital of the University of Pennsylvania was 3.8% compared with 1.3% at Pennsylvania Hospital (P=.283). Of note, 3 women (37.5%) who were initially asymptomatic developed mild symptoms in the 2 weeks after a positive test result. Repeat severe acute respiratory syndrome coronavirus 2 testing was performed in 14 of the 310 women (4.5%) who initially had a negative result; 2 women (0.6%) had a positive result on repeat testing. Moreover, 242 (78.1%) and 213 (68.7%) of the 310 women who had a negative result for severe acute respiratory syndrome coronavirus 2 at the time of the initial hospitalization were followed up via telephone at 1 and 2 weeks after admission, respectively. Viral symptoms, including fevers, chills, shortness of breath, or cough, were self-reported in 4.5% and 4.2% of these women at 1 and 2 weeks after discharge, respectively. Conclusion: The asymptomatic positive severe acute respiratory syndrome coronavirus 2 test rate among an obstetrical population in Philadelphia differed between 2 hospitals and was lower than that described in other geographic regions. This supports the importance of institution-specific testing protocols. The development of symptomatic severe acute respiratory syndrome coronavirus 2 infection after hospitalization among women with initial negative test results is uncommon.

SARS-CoV-2 Genomic Variation in Space and Time in Hospitalized Patients in Philadelphia.

The severe acute respiratory coronavirus 2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. The epidemic accelerated in Philadelphia, PA, in the spring of 2020, with the city experiencing a first peak of infections on 15 April, followed by a decline through midsummer. Here, we investigate spread of the epidemic in the first wave in Philadelphia using full-genome sequencing of 52 SARS-CoV-2 samples obtained from 27 hospitalized patients collected between 30 March and 17 July 2020. Sequences most commonly resembled lineages circulating at earlier times in New York, suggesting transmission primarily from this location, though a minority of Philadelphia genomes matched sequences from other sites, suggesting additional introductions. Multiple genomes showed even closer matches to other Philadelphia isolates, suggestive of ongoing transmission within Philadelphia. We found that all of our isolates contained the D614G substitution in the viral spike and belong to lineages variously designated B.1, Nextstrain clade 20A or 20C, and GISAID clade G or GH. There were no viral sequence polymorphisms detectably associated with disease outcome. For some patients, genome sequences were determined longitudinally or concurrently from multiple body sites. In both cases, some comparisons showed reproducible polymorphisms, suggesting initial seeding with multiple variants and/or accumulation of polymorphisms after infection. These results thus provide data on the sources of SARS-CoV-2 infection in Philadelphia and begin to explore the dynamics within hospitalized patients.IMPORTANCE Understanding how SARS-CoV-2 spreads globally and within infected individuals is critical to the development of mitigation strategies. We found that most lineages in Philadelphia had resembled sequences from New York, suggesting infection primarily but not exclusively from this location. Many genomes had even nearer neighbors within Philadelphia, indicating local spread. Multiple genome sequences were available for some subjects and in a subset of cases could be shown to differ between time points and body sites within an individual, indicating heterogeneous viral populations within individuals and raising questions on the mechanisms responsible. There was no evidence that different lineages were associated with different outcomes in patients, emphasizing the importance of individual-specific vulnerability.