Stability of SARS-CoV-2 variants of concern (Delta and Omicron) on surfaces at room temperature.

Surfaces contaminated with infectious SARS-CoV-2 particles have the potential to cause human infection and any increase in surface survivability of a SARS-CoV-2 variant may increase its prevalence over other variants. This study investigated whether there were differences in surface persistence between Delta and Omicron variants leading to Omicron's dominance globally. Stainless steel coupons were inoculated with suspensions of either Delta or Omicron variant and exposed to typical environmental conditions within a containment level 3 laboratory. Coupons were recovered at different timepoints and enumerated using plaque assay. Both variants were recoverable for >48 h on the coupons. Omicron showed a greater reduction of viability after 48 h compared to Delta with a 20-fold decrease versus 15-fold respectively, but this difference was not statistically significant (p = 0.424). These results indicate that Omicron's surface persistence is unlikely to contribute to it becoming the dominant variant over Delta.

Impact of the SARS-CoV-2 pandemic on the health of individuals with intoxication-type metabolic diseases-Data from the E-IMD consortium.

The SARS-CoV-2 pandemic challenges healthcare systems worldwide. Within inherited metabolic disorders (IMDs) the vulnerable subgroup of intoxication-type IMDs such as organic acidurias (OA) and urea cycle disorders (UCD) show risk for infection-induced morbidity and mortality. This study (observation period February 2020 to December 2021) evaluates impact on medical health care as well as disease course and outcome of SARS-CoV-2 infections in patients with intoxication-type IMDs managed by participants of the European Registry and Network for intoxication type metabolic diseases Consortium (E-IMD). Survey's respondents managing 792 patients (n = 479 pediatric; n = 313 adult) with intoxication-type IMDs (n = 454 OA; n = 338 UCD) in 14 countries reported on 59 (OA: n = 36; UCD: n = 23), SARS-CoV-2 infections (7.4%). Medical services were increasingly requested (95%), mostly alleviated by remote technologies (86%). Problems with medical supply were scarce (5%). Regular follow-up visits were reduced in 41% (range 10%-50%). Most infected individuals (49/59; 83%) showed mild clinical symptoms, while 10 patients (17%; n = 6 OA including four transplanted MMA patients; n = 4 UCD) were hospitalized (metabolic decompensation in 30%). ICU treatment was not reported. Hospitalization rate did not differ for diagnosis or age group (p = 0.778). Survival rate was 100%. Full recovery was reported for 100% in outpatient care and 90% of hospitalized individuals. SARS-CoV-2 impacts health care of individuals with intoxication-type IMDs worldwide. Most infected individuals, however, showed mild symptoms and did not require hospitalization. SARS-CoV-2-induced metabolic decompensations were usually mild without increased risk for ICU treatment. Overall prognosis of infected individuals is very promising and IMD-specific or COVID-19-related complications have not been observed.

Mortality rates among hospitalized patients with COVID-19 treated with convalescent plasma: A Systematic review and meta-analysis (preprint)

Abstract IMPORTANCE. Many hospitalized patients with COVID-19 have been treated with convalescent plasma. However, it is uncertain whether this therapy lowers mortality and if so, if the mortality benefit is larger among specific subgroups, such as recipients of plasma with high antibody content and patients treated early in the disease course. OBJECTIVE. To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. DATA SOURCES. On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature. STUDY SELECTION. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3,841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of five reviewers. DATA EXTRACTION AND SYNTHESIS. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using inverse-variance random-effects model. MAIN OUTCOMES AND MEASURES. Prespecified end point was all-cause mortality during hospitalization. RESULTS. Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses demonstrated that transfusion of COVID-19 convalescent plasma was associated with a significant decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio (OR), 0.87 [95% CI, 0.76-1.00]) and matched cohort studies (OR, 0.77 [95% CI, 0.64-0.94]). Meta-analysis of subgroups revealed two important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared to convalescent plasma containing low antibody levels (OR, 0.85 [95% CI, 0.73 to 0.99]). Second, earlier treatment with COVID-19 convalescent plasma was associated with a significant decrease in mortality compared with the later treatment cohort (OR, 0.63 [95% CI, 0.48 to 0.82]). CONCLUSIONS AND RELEVANCE. COVID-19 convalescent plasma use was associated with a 13% reduced risk in mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

OS USOS DE AGAMBEN EM TEMPOS DE PANDEMIA

O presente trabalho realiza uma análise do papel paradoxal cumprido pelos escritos do filósofo Giorgio Agamben na pandemia do coronavírus. Com diversas intervenções minimizando a gravidade da pandemia e criticando as medidas sanitárias adotadas pelo governo italiano, Agamben se tornou objeto constante de crítica. Apesar de sua postura pessoal, contudo, o presente trabalho busca mostrar a utilidade da filosofia de Agamben para entender o nosso contexto atual.Alternate :This work offers an analysis of the paradoxical role played by the writings of Giorgio Agamben during the covid pandemic. With several interventions minimizing the seriousness of the disease and criticizing the sanitary measures adopted by the Italian government, Agamben became object of constant criticisms. Despite his stance, however, this work aims to show the utility of Agamben's philosophy to understand our present context.

Exploring COVID-19 vaccine uptake, hesitancy, and disease-related beliefs in people with multiple sclerosis

Introduction: People with multiple sclerosis (MS) are vulnerable to severe outcomes from COVID-19 infection and were prioritised for COVID-19 vaccination in Australia from March 2021. Despite this, vaccine hesitancy may hinder optimal vaccination uptake. Aim(s): This study explored COVID-19 vaccine uptake, beliefs, and hesitancy in people with MS. Method(s): People with MS receiving MS healthcare management at two Australian health services were invited to participate in an online survey, between September and October 2021. The survey collected sociodemographic and disease-specific characteristics, as well as vaccine status, vaccine hesitancy and beliefs towards COVID-19 vaccination using validated scales: the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale, and the Disease Influenced Vaccine Acceptance Scale-Six. Regression analyses were used. Result(s): Of the 281 people with MS (mean age 47.7 [SD 12.8] years;75.8% females) who participated, 82.9% had received >=1 COVID-19 vaccine dose. There were 17.1% who were unvaccinated, of which 51.2% reported they were likely to accept vaccination in future. Younger participants were less likely to be vaccinated (B[SE] 0.05[0.01]), as were those within 1-5 years disease duration (B[SE] -1.17[0.39]), all p<0.05. Compared to vaccinated participants, unvaccinated participants reported higher vaccine hesitancy (B[SE] 9.66 [0.72]), greater negative attitudes around vaccine complacency and confidence (B[SE] 13.36[1.40]), greater complacency toward COVID-19 in the context of MS (B[SE] 1.80[0.50]), and higher MS interaction concerns (B[SE] 3.38[0.52]), all p<0.001. Participants who reported no impact of MS on their daily life had lower concerns about the impact of COVID-19 vaccination on MS treatments or disease progression, compared with those reporting MS impacted their daily life all of the time (B[SE] -2.00[0.66], p=0.002). Conclusion(s): General and disease-specific COVID-19 vaccine concerns may influence uptake for people with MS. Understanding the reasons for hesitancy and how they correlate with MS disease and treatment interaction concerns may inform tailored education messages at individual and population levels that addresses these concerns, particularly for ongoing booster doses.

Applying Marketing Intelligence System in Improving Marketing Performance for Jordanian Corporations During COVID19 Pandemic

The research looks at how a marketing intelligence system might help Jordanian businesses improve their marketing effectiveness in the wake of the COVID19 Pandemic. The study’s sample size includes 234 Jordanian marketing managers. A stratified random sample of 146 Jordanian firms was chosen, and 118 valid questionnaires were obtained from marketing managers for statistical analysis, yielding an 80.8% response rate. According to the findings, the marketing intelligence system is crucial in influencing the company’s marketing performance, and its simple and practical design increases the possibility of benefiting from it in improving the company’s marketing performance. The researchers recommend allocating a separate department for marketing intelligence systems in order to maximize the system’s benefit in terms of improving Jordanian corporations’ marketing performance, as well as involving the department’s director in various strategic decisions affecting the company. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The aerobiology of SARS-CoV-2 in UK hospitals and the impact of aerosol generating procedures (preprint)

BackgroundSARS-CoV-2 nosocomial transmission to patients and healthcare workers (HCWs) has occurred throughout the COVID-19 pandemic. Aerosol generating procedures (AGPs) seemed particularly risky, and policies have restricted their use in all settings. We examined the prevalence of aerosolized SARS-CoV-2 in the rooms of COVID-19 patients requiring AGP or supplemental oxygen compared to those on room air. MethodsSamples were collected prospectively near to adults hospitalised with COVID-19 at two tertiary care hospitals in the UK from November 2020 - October 2021. The Sartorius MD8 AirPort air sampler was used to collect air samples at a minimum distance of 1.5 meters from patients. RT-qPCR was used following overnight incubation of membranes in culture media and extraction. ResultsWe collected 219 samples from patients rooms: individuals on room air (n=67), receiving oxygen (n=65) or AGP (n=67). Of these, 54 (24.6%) samples were positive for SARS-CoV-2 viral RNA. The highest prevalence was identified in the air around patients receiving oxygen (32.3%, n=21, CI95% 22.2 to 44.3%) with AGP and room air recording prevalence of (20.7%, n=18, CI95% 14.1 - 33.7%) and (22.3%, n=15, CI95% 13.5 - 30.4%) respectively. We did not detect a significant difference in the observed frequency of viral RNA between interventions. InterpretationSARS-CoV-2 viral RNA was detected in the air of hospital rooms of COVID-19 patients, and AGPs did not appear to impact the likelihood of viral RNA. Enhanced respiratory protection and appropriate infection prevention and control measures are required to be fully and carefully implemented for all COVID-19 patients to reduce risk of aerosol transmission.

Coagulation profile of human COVID-19 convalescent plasma.

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

THE GAMESTOP EPISODE: WHAT HAPPENED AND WHAT DOES IT MEAN?

The decline in trading fees and commissions is offset by net interest on customers' cash balances, stock lending fees, and payment for order flow (PFOF) by wholesale market makers that execute the trades. Robinhooďs platform had experienced service interruptions during the early pandemic period of high stock market volatility in March 2020, leading to investigations by the SEC, FINRA, and authorities in several states. The House Financial Services and Senate Banking Committees held public hearings in February, March, and May, summoning a Robinhood founder, an investor active on Reddit, the head of Citadel Securities, a market maker making PFOF to Robinhood, and others to testify. There had been a steady increase in the ratio of debt to GDP in the United States prior to the crisis, led primarily by households and the financial sector. Since 2008, the increase has continued, now as a result of large-scale borrowing by the federal government and nonfinancial corporate sectors, and, most recently, the sharp increase associated with the Covid pandemic.

Entrepreneurial responses to uncertainties during the COVID-19 recovery: A longitudinal study of B&Bs in Zhangjiajie, China.

The COVID-19 pandemic has brought sweeping changes to global tourism alongside large-scale travel restrictions, posing complex challenges to entrepreneurs and firms seeking to find their footing in a turbulent climate. This study presents a theoretical framework linking uncertainty, capital, and innovation to analyse how bed-and-breakfast small and medium-sized enterprises have innovatively responded to unprecedented obstacles during COVID-19 recovery. Three-stage longitudinal interviews were conducted with more than 30 entrepreneurs between April and November 2020 to unpack their ongoing responses to the pandemic. The recovery process was found to be non-linear due to the shifting nature of sources of uncertainty and changes in entrepreneurs' capital. These alterations shaped interviewees' responses, especially in terms of product and marketing innovations, which ultimately generated new uncertainty.

An outbreak of SARS-CoV-2 in a public-facing office in England, 2021 (preprint)

Between August-September 2021, an outbreak of SARS-CoV-2, with an attack rate of 55% (22/40 workers), occurred in a public-facing office in England. To identify workplace and worker-related risk factors, a comprehensive investigation involving surface sampling, environmental assessment, molecular and serological testing, and worker questionnaires was performed between 3 September and 27 October 2021. The results affirm the utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies.

Operational Innovation in the Provision of Pediatric Extracorporeal Membrane Oxygenation for Multisystem Inflammatory Syndrome in Children.

Treatment of multisystem inflammatory syndrome in children (MIS-C) can require significant critical care resources. Our aim is to alert mixed pediatric and adult hospitals worldwide of the possibility that pediatric and adult patients may simultaneously require cannulation to extracorporeal membrane oxygenation (ECMO) for MIS-C and severe COVID-19. We conducted a retrospective review of operations required to treat cardiogenic shock in 3 pediatric patients with a diagnosis of MIS-C admitted to a single medium-sized pediatric referral center located within a large academic medical center over a 14-day period. At this time, a large number of adult patients required ECMO for severe COVID-19 at our institution. Of the 11 pediatric patients who presented with MIS-C during the first surge of 2020, 2 patients required cannulation to venoarterial extracorporeal membrane oxygenation (VA-ECMO), and a third patient developed a life-threatening arrhythmia requiring transfer to a neighboring institution for consideration of VA-ECMO when our institution's ECMO capacity had briefly been reached. Pediatric referral centers located within institutions providing ECMO to adult patients with severe COVID-19 may benefit from frequent and direct communication with their adult and regional colleagues to devise a collaborative plan for safe and timely provision of ECMO to patients with MIS-C as the ongoing pandemic continues to consume this limited, lifesaving resource.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Risk, uncertainty and ambiguity amid Covid-19: A multi-national analysis of international travel intentions.

This study analyses how Covid-19 shapes individuals' international tourism intentions in context of bounded rationality. It provides a novel analysis of risk which is disaggregated into tolerance/aversion of and competence to manage risks across three different aspects: general, domain (tourism) and situational (Covid-19). The impacts of risk are also differentiated from uncertainty and ambiguity. The empirical study is based on large samples (total = 8962) collected from the world's top five tourism source markets: China, USA, Germany, UK and France. Various risk factors show significant predictive powers of individual's intentions to defer international tourism plans amid Covid-19. Uncertainty and ambiguity intolerance is shown to lead to intentions to take holidays relatively sooner rather than delaying the holiday plans.

An Innovative Approach to Modeling VIPER Rover Software Life Cycle Cost

NASAs Volatiles Investigating Polar Exploration Rover (VIPER) will be the first robotic mission to prospect for water ice near the south pole of the Moon in late 2023 on a 100 Earth-day mission. The information that the VIPER rover provides will help improve understanding of the composition, distribution, and accessibility of Lunar polar volatiles and will help determine howthe Moons resources can support future human space exploration. VIPER, however, represents a radical departure from the way that NASA has traditionally developed planetary robotic missions. A key consequence of these differences is that estimating the cst of VIPERs rover software is challenging and complex. For example, VIPER is being developed using management procedures typically applied to NASA research and technology projects, rather than space flight programs. In addition, key portions of the rovers software are being designed as ground software to run on mission control computers (rather than on board the rover as flight software as with prior planetary missions) taking advantage of continuous, interactive data communications between the Moon and Earth and higher performance computing available on the ground. Moreover, the rovers software is being engineered using Agile software development practices and incorporates a significant amount of open-source code rather than following traditional (spir al, waterfall, etc.) development methods and mouse code. In this paper, we present an innovative process to estimate the life cycle cost of VIPERs rover software. We first describe how we modeled the architecture and code counts for three software elements: Rover Flight Software (RFSW), Rover Ground Software (RGSW), and Rover Simulation Software (RSIM). We then discuss key challenges and unique aspects of our approach, such as the lack of Lunar rover analogies, the need to integrate and test large opersource software, and the strategie developed to account for use of nonspace flight management practices and the impact of the COVID-19 pandemic We conclude with a summary of our results, including cumulative distribution, nearest neighbors and clusteanalysis, as well as heuristics used to confirm the reasonableness of the cost estimate.

Early safety indicators of COVID-19 convalescent plasma in 5000 patients.

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.