Real-World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) were authorized for the treatment of COVID-19 outpatients based on clinical trials completed early in the pandemic, which were underpowered for mortality and subgroup analyses. Real-world data studies are promising for further assessing rapidly deployed therapeutics. RESEARCH QUESTION: Did mAb treatment prevent progression to severe disease and death across pandemic phases and based on risk factors, including prior vaccination status? STUDY DESIGN AND METHODS: This observational cohort study included nonhospitalized adult patients with SARS-CoV-2 infection from November 2020 to October 2021 using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAb treatment under emergency use authorization. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and hospitalization severity. RESULTS: Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 patients not receiving mAbs. Compared with mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR, 0.48; 95% CI, 0.38-0.60) and all-cause mortality (0.1% vs 0.9%; adjusted OR, 0.11; 95% CI, 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs 8.5 days) and lower risk of mechanical ventilation (4.6% vs 16.6%). Results were similar for preventing hospitalizations during the Delta variant phase (adjusted OR, 0.35; 95% CI, 0.25-0.50) and across subgroups. Number-needed-to-treat (NNT) to prevent hospitalization was lower for subgroups with higher baseline risk of hospitalization; for example, multiple comorbidities (NNT = 17) and not fully vaccinated (NNT = 24) vs no comorbidities (NNT = 88) and fully vaccinated (NNT = 81). INTERPRETATION: Real-world data revealed a strong association between receipt of mAbs and reduced hospitalization and deaths among COVID-19 outpatients across pandemic phases. Real-world data studies should be used to guide practice and policy decisions, including allocation of scarce resources.

Building a Real-Time Remote Patient Monitoring Patient Safety Program for COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) pandemic has forced providers to rapidly adopt telehealth tools to reduce staff exposure to ill persons, preserve personal protective equipment, and minimize impact of patient surges on facilities. Remote patient monitoring (RPM) can be used to monitor high-risk patients from their homes and open up hospital bed availability. The authors describe a pilot program to evaluate the impact of RPM in postdischarge monitoring of COVID-19 patients. High-risk patients discharging from the hospital received a wearable vital sign monitoring device to be worn for 8 consecutive days, allowing real-time data transmission to a virtual health center (VHC), which had been established prior to the pandemic, via a smart phone application. The data were monitored 24 hours a day by a VHC tech with built-in escalation protocols to a nurse and/or an attending physician if needed. Eighty patients were enrolled, 48% women with an age range of 19-83 years. Languages included Spanish (49%), English (47%), Burmese (2%), and Swahili (1%). The most common comorbidities included hypertension (48%) and diabetes mellitus (48%). Oxygen was the most common addressed need; 8% requiring new oxygen and 8% benefitting from oxygen-weaning during the RPM time period. Ten percent patients had emergency department (ED) visits and 4% were readmitted within 30 days of discharge. The authors built and deployed an RPM program for postdischarge monitoring of high-risk patients. RPM can be quickly deployed to support COVID-19 patients postdischarge and assist with hospital capacity. RPM can be rapidly and successfully deployed during the COVID 19 pandemic to aid in transitions of care.

Digital restoration of the Wilson-Leonard 2 Paleoindian skull (~10,000 BP) from central Texas with comparison to other early American and modern crania.

OBJECTIVES: Craniofacial morphology (CFM) is often used to address questions about the biological affinities of the earliest Americans, or Paleoindians, but resolution is complicated in part by a lack of well-preserved crania. The Wilson-Leonard 2 (WL-2) Paleoindian skull from Texas has never been fully analyzed because it is crushed and cannot be physically reconstructed. This study employs a digital restoration for comprehensive assessment and analysis of WL-2. MATERIALS AND METHODS: High-resolution CT data and geometric morphometrics are used to restore the WL-2 skull and analyze its morphology using 65 craniometric measurements acquired on the restoration. These data allow for a full morphological description and multivariate (Mahalanobis Distance and Principal Component) comparisons to other Paleoindians and recent populations. RESULTS: WL-2 has a long, narrow braincase, and a short, modestly prognathic face. Compared with other Paleoindians, she is individually similar to several skulls from Brazil, but aligns most closely with pooled samples from the US and Mexico. WL-2 is most similar to recent populations from Europe, Asia, and the Americas, and markedly different to those from Africa and Australia. DISCUSSION: The overall morphology of WL-2 and her association with Asians and Europeans align well with trends identified in other CFM analyses. Her affinity to recent Amerindians contrasts with the findings of many previous CFM studies, but is seemingly consistent with molecular analyses suggesting a close relationship between some Paleoindians and modern American Indians. This study demonstrates the potential for using digital anthropological methods to study other Paleoindian crania whose data value is limited by physical destruction and/or deformation.

Solar-Aligned Pictographs at the Paleoindian Site of Painel do Pilão along the Lower Amazon River at Monte Alegre, Brazil.

The archaeological sites near Monte Alegre, along Brazil's lower Amazon River, provide new information on the little-known activities and symbolism of South American Paleoindians toward the end of the Ice Age. While paleoindian sites like Monte Verde in Chile, or Guitarrero Cave in Peru, are located near the pacific coast, Monte Alegre lies much further inland, 680 km upriver from the mouth of the Amazon River and the Atlantic Coast. With excavated wood charcoal radiocarbon dated as early as 13,200 calibrated years ago, the hill-as a source of sandstone and quartz lithics-supplied early pioneers with adequate tools needed for colonizing the interior of the continent. Once there, they painted rock art on the landscape, which bears a record of the sun's horizon positions throughout the year. At just 2° south of the equator, Monte Alegre shows no overt seasonal changes beyond fluctuating rainfall amounts, unlike at higher latitudes where temperature, amount of daylight, foliage, and forms of precipitation markedly change. Near the equator, solar and stellar horizon sightings most visibly track the passage of time and seasonal cycles. However, horizons are often hidden behind high forest canopy throughout much of the Amazon Rainforest; but in the Monte Alegre hill ridges looming above the river, paleoindians could hike above the canopy to peer at the horizon, more effectively synchronizing their activities to ecological cycles. This research suggests that Monte Alegre paleoindians delimited the azimuthal range of the sun in a solar year with notational pictographs aligned to horizon sightings at Painel do Pilão, and leaving a painted grid of tally marks that might have served as a rudimentary early calendar. The broad-reaching implication for early Americans is that through the strategic placement of rock art, these ancient artists fostered predictive archaeorecording from which resources could be optimally extracted, ceremonial activities could be consistently scheduled, and gatherings for social and economic exchange could be more efficiently coordinated.

Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from Recife, Brazil.

BACKGROUND: The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. METHODOLOGY/PRINCIPAL FINDINGS: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. CONCLUSIONS/SIGNIFICANCE: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions.

All-cause mortality after diabetes-related amputation in Barbados: a prospective case-control study.

OBJECTIVE: To determine the mortality rate after diabetes-related lower-extremity amputation (LEA) in an African-descent Caribbean population. RESEARCH DESIGN AND METHODS: We conducted a prospective case-control study. We recruited case subjects (with diabetes and LEA) and age-matched control subjects (with diabetes and no LEA) between 1999 and 2001. We followed these groups for 5 years to assess mortality risk and causes. RESULTS: There were 205 amputations (123 minor and 82 major). The 1-year and 5-year survival rates were 69 and 44% among case subjects and 97 and 82% among control subjects (case-control difference, P < 0.001). The mortality rates (per 1,000 person-years) were 273.9 (95% CI 207.1-362.3) after a major amputation, 113.4 (85.2-150.9) after a minor amputation, and 36.4 (25.6-51.8) among control subjects. Sepsis and cardiac disease were the most common causes of death. CONCLUSIONS: These mortality rates are the highest reported worldwide. Interventions to limit sepsis and complications from cardiac disease offer a huge potential for improving post-LEA survival in this vulnerable group.