Lessons learned from the use of COVID-19 convalescent plasma at Kaiser Permanente.

Background: In April 2020, the Mayo Clinic helped establish the US Food and Drug Administration Expanded Access Protocol for COVID-19 (coronavirus disease 2019) convalescent plasma (CCP). The effectiveness of CCP in the published literature is contradictory because some retrospective studies showed benefit in reducing mortality and severe illness, whereas prospective randomized controlled trials demonstrated no benefit of CCP. Objectives: To discuss (1) the implementation of CCP across Kaiser Permanente Southern California between April 2020 and April 2021, (2) retrospective multivariable analysis of 2,831 patients with COVID-19 who were transfused with CCP compared with 18,475 patients with COVID-19 who did not receive CCP, (3) how to reconcile contradictory published data regarding the efficacy of CCP, and (4) guidance regarding the future use of convalescent plasma in a large community hospital setting. Methods: Multivariable analysis was controlled for demographic characteristics, level of oxygen delivery, intensive care unit stay, selected laboratory findings, and other concurrent treatment-related variables. Tubing segments from 151 CCP units transfused between October 2020 and April 2021 were retrospectively tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike protein receptor-binding domain IgG. Multivariable analysis showed that CCP transfusion did not affect mortality rates at 30 days and 5 months (odds ratio, 1.04, 95% CI, 0.87-1.25, and hazard ratio, 1.05, 95% CI, 0.93-1.19). Conclusions: If convalescent plasma is offered as a therapeutic in a future viral pandemic, we recommend (1) transfusing only those patients who are negative for neutralizing antibodies, (2) transfusing very early during the disease course, (3) only using convalescent plasma with known levels of neutralizing antibodies, or (4) alternatively providing fractionated hyperimmune globulin.

Critical Capability Needs for Reduction of Transmission of SARS-CoV-2 Indoors.

Coordination of efforts to assess the challenges and pain points felt by industries from around the globe working to reduce COVID-19 transmission in the indoor environment as well as innovative solutions applied to meet these challenges is mandatory. Indoor infectious viral disease transmission (such as coronavirus, norovirus, influenza) is a complex problem that needs better integration of our current knowledge and intervention strategies. Critical to providing a reduction in transmission is to map the four core technical areas of environmental microbiology, transmission science, building science, and social science. To that end a three-stage science and innovation Summit was held to gather information on current standards, policies and procedures applied to reduce transmission in built spaces, as well as the technical challenges, science needs, and research priorities. The Summit elucidated steps than can be taken to reduce transmission of SARS-CoV-2 indoors and calls for significant investments in research to enhance our knowledge of viral pathogen persistence and transport in the built environment, risk assessment and mitigation strategy such as processes and procedures to reduce the risk of exposure and infection through building systems operations, biosurveillance capacity, communication form leadership, and stakeholder engagement for optimal response. These findings reflect the effective application of existing knowledge and standards, emerging science, and lessons-learned from current efforts to confront SARS-CoV-2.

Lessons learned in managing risk: Tools and strategies for confident operations from the CLEAN 2020 Summit.

Risk mitigation of COVID-19 in the indoor environment requires an articulated strategy for creating a bridge between science and the business community that focuses on knitting together four core capabilities-environmental microbiology, transmission science, building science, and social science-advancing scientific knowledge. The purpose of this article is to share insights from the CLEAN 2020 Summit, which assembled leaders from business, policy, standards development, science, and engineering working to mitigate risk of transmission in the built environment. The Summit worked to assess current challenges and pain points felt by industries from around the globe as well as innovative solutions applied to meet these challenges. Although SARS-CoV-2 and the COVID-19 diseases are unique, the foundation of knowledge to assess and mitigate the risk of viral transmission in the built environment is robust. There are opportunities to improve science and engineering technology solutions, processes, and procedures to better meet the dynamic needs of the evolving pandemic.

Nano-metal oxides: Exposure and engineering control assessment.

In January 2007, the National Institute for Occupational Safety and Health (NIOSH) conducted a field study to evaluate process specific emissions during the production of ENMs. This study was performed using the nanoparticle emission assessment technique (NEAT). During this study, it was determined that ENMs were released during production and cleaning of the process reactor. Airborne concentrations of silver, nickel, and iron were found both in the employee's personal breathing zone and area samples during reactor cleaning. At the completion of this initial survey, it was suggested that a flanged attachment be added to the local exhaust ventilation system. NIOSH re-evaluated the facility in December 2011 to assess worker exposures following an increase in production rates. This study included a fully comprehensive emissions, exposure, and engineering control evaluation of the entire process. This study made use of the nanoparticle exposure assessment technique (NEAT 2.0). Data obtained from filter-based samples and direct reading instruments indicate that reactor cleanout increased the overall particle concentration in the immediate area. However, it does not appear that these concentrations affect areas outside of the production floor. As the distance between the reactor and the sample location increased, the observed particle number concentration decreased, creating a concentration gradient with respect to the reactor. The results of this study confirm that the flanged attachment on the local exhaust ventilation system served to decrease exposure potential. Given the available toxicological data of the metals evaluated, caution is warranted. One should always keep in mind that occupational exposure levels were not developed specifically for nanoscale particles. With data suggesting that certain nanoparticles may be more toxic than the larger counterparts of the same material; employers should attempt to control emissions of these particles at the source, to limit the potential for exposure.

Multigeneration Cross-Contamination of Mail with Bacillus anthracis Spores.

The release of biological agents, including those which could be used in biowarfare or bioterrorism in large urban areas, has been a concern for governments for nearly three decades. Previous incidents from Sverdlosk and the postal anthrax attack of 2001 have raised questions on the mechanism of spread of Bacillus anthracis spores as an aerosol or contaminant. Prior studies have demonstrated that Bacillus atrophaeus is easily transferred through simulated mail handing, but no reports have demonstrated this ability with Bacillus anthracis spores, which have morphological differences that may affect adhesion properties between spore and formite. In this study, equipment developed to simulate interactions across three generations of envelopes subjected to tumbling and mixing was used to evaluate the potential for cross-contamination of B. anthracis spores in simulated mail handling. In these experiments, we found that the potential for cross-contamination through letter tumbling from one generation to the next varied between generations while the presence of a fluidizer had no statistical impact on the transfer of material. Likewise, the presence or absence of a fluidizer had no statistically significant impact on cross-contamination levels or reaerosolization from letter opening.

Refinement of the Nanoparticle Emission Assessment Technique into the Nanomaterial Exposure Assessment Technique (NEAT 2.0).

Engineered nanomaterial emission and exposure characterization studies have been completed at more than 60 different facilities by the National Institute for Occupational Safety and Health (NIOSH). These experiences have provided NIOSH the opportunity to refine an earlier published technique, the Nanoparticle Emission Assessment Technique (NEAT 1.0), into a more comprehensive technique for assessing worker and workplace exposures to engineered nanomaterials. This change is reflected in the new name Nanomaterial Exposure Assessment Technique (NEAT 2.0) which distinguishes it from NEAT 1.0. NEAT 2.0 places a stronger emphasis on time-integrated, filter-based sampling (i.e., elemental mass analysis and particle morphology) in the worker's breathing zone (full shift and task specific) and area samples to develop job exposure matrices. NEAT 2.0 includes a comprehensive assessment of emissions at processes and job tasks, using direct-reading instruments (i.e., particle counters) in data-logging mode to better understand peak emission periods. Evaluation of worker practices, ventilation efficacy, and other engineering exposure control systems and risk management strategies serve to allow for a comprehensive exposure assessment.

Anthrax letters in an open office environment: effects of selected CDC response guidelines on personal exposure and building contamination.

In 2001, letters filled with a powder containing anthrax (Bacillus anthracis) spores were delivered by mail to a number of governmental and media locations within the United States. In response, the U.S. Centers for Disease Control and Prevention (CDC) provided guidelines for office personnel who might encounter a letter containing suspicious powder. These guidelines were developed during the crisis and in the absence of experimental data from laboratory or field investigations. An obvious need thus exists for quantitative and scientific verification for validation of these guidelines. This study attempts to address this need, adapting earlier work that used a multiple small office test site to create a model system in an open office test site in a vacated office building in which Bacillus atrophaeus spores (as a simulant for B. anthracis spores) were released by opening a letter. Using SF(6) as a tracer gas, smoke tubes (containing stannic chloride) to visualize airflow, culturable aerosol sampling, and aerosol spectrometry we were able to characterize airflow and unmitigated spore aerosol dissemination within the office test site. Subsequently, two scripted test scenarios were used to reproduce selected portions of the existing CDC response guidelines and a modified version where the contaminated letter opener warned co-workers to evacuate then waited 5 min before doing so himself. By not leaving together with other co-workers, the risk of the letter opener cross-contaminating others was eliminated. The total potential spore aerosol exposure of the letter opener was not affected by remaining still and waiting 5 min to allow co-workers to escape first before leaving the office. Closing office doors and quickly deactivating the heating, ventilation, and air conditioning system significantly reduced spore aerosol concentrations outside the main open office in which they had been released.

Multigeneration cross contamination of mail with Bacillus species spores by tumbling.

In 2001, envelopes loaded with Bacillus anthracis spores were mailed to Senators Daschle and Leahy as well as to the New York Post and NBC News buildings. Additional letters may have been mailed to other news agencies because there was confirmed anthrax infection of employees at these locations. These events heightened the awareness of the lack of understanding of the mechanism(s) by which objects contaminated with a biological agent might spread disease. This understanding is crucial for the estimation of the potential for exposure to ensure the appropriate response in the event of future attacks. In this study, equipment to simulate interactions between envelopes and procedures to analyze the spread of spores from a "payload" envelope (i.e., loaded internally with a powdered spore preparation) onto neighboring envelopes were developed. Another process to determine whether an aerosol could be generated by opening contaminated envelopes was developed. Subsequent generations of contaminated envelopes originating from a single payload envelope showed a consistent two-log decrease in the number of spores transferred from one generation to the next. Opening a tertiary contaminated envelope resulted in an aerosol containing 10(3) B. anthracis spores. We developed a procedure for sampling contaminated letters by a nondestructive method aimed at providing information useful for consequence management while preserving the integrity of objects contaminated during the incident and preserving evidence for law enforcement agencies.

A new Lower Pleistocene archeological site in Europe (Vallparadis, Barcelona, Spain).

Here we report the discovery of a new late Lower Pleistocene site named Vallparadís (Barcelona, Spain) that produced a rich archeological and paleontological sequence dated from the upper boundary of the Jaramillo subchron to the early Middle Pleistocene. This deposit contained a main archeological layer with numerous artifacts and a rich macromammalian assemblage, some of which bore cut marks, that could indicate that hominins had access to carcasses. Paleomagnetic analysis, electron spin resonance-uranium series (ESR-US), and the biostratigraphic chronological position of the macro- and micromammal and lithic assemblages of this layer reinforce the proposal that hominins inhabited Europe during the Lower Pleistocene. The archeological sequence provides key information on the successful adaptation of European hominins that preceded the well-known fossil population from Atapuerca and succeeded the finds from Orce basin. Hence, this discovery enables us to close a major chronological gap in the early prehistory of Iberia. According to the information in this paper and the available data from these other sites, we propose that Mediterranean Western Europe was repeatedly and perhaps continuously occupied during the late Matuyama chron.

Responding to detection of aerosolized Bacillus anthracis by autonomous detection systems in the workplace.

Autonomous detection systems (ADSs) are under development to detect agents of biologic and chemical terror in the environment. These systems will eventually be able to detect biologic and chemical hazards reliably and provide approximate real-time alerts that an agent is present. One type of ADS that tests specifically for Bacillus anthracis is being deployed in hundreds of postal distribution centers across the United States. Identification of aerosolized B. anthracis spores in an air sample can facilitate prompt on-site decontamination of workers and subsequent administration of postexposure prophylaxis to prevent inhalational anthrax. Every employer who deploys an ADS should develop detailed plans for responding to a positive signal. Responding to ADS detection of B. anthracis involves coordinating responses with community partners and should include drills and exercises with these partners. This report provides guidelines in the following six areas: 1) response and consequence management planning, including the minimum components of a facility response plan; 2) immediate response and evacuation; 3) decontamination of potentially exposed workers to remove spores from clothing and skin and prevent introduction of B. anthracis into the worker's home and conveyances; 4) laboratory confirmation of an ADS signal; 5) steps for evaluating potentially contaminated environments; and 6) postexposure prophylaxis and follow-up.

Rapid detection and determination of the aerodynamic size range of airborne mycobacteria associated with whirlpools.

Novel environmental air and water mycobacteria sampling and analytical methods are needed to circumvent difficulties associated with the use of culture-based methodologies. To implement this objective, a commercial, clinical, genus DNA amplification method utilizing the polymerase chain reaction (PCR) was interfaced with novel air sampling strategies in the laboratory. Two types of air samplers, a three-piece plastic, disposable filter cassette and an eight-stage micro-orifice uniform deposit impactor (MOUDI), were used in these studies. In both samplers, 37-mm polytetrafluoroethylene (PTFE) filters were used. Use of the MOUDI sampler permitted the capture of airborne mycobacteria in discrete size ranges, an important parameter for relating the airborne mycobacteria cells to potential respirable particles (aerodynamic diameter <10 microm) capable of causing health effects. Analysis of the samples was rapid, requiring only 1-1.5 days, as no microbial culturing or DNA purification was required. This approach was then used to detect suspected mycobacteria contamination associated with pools at a large public facility. PCR was also used to analyze various water samples from these pools. Again, no culturing or sample purification was required. Water samples taken from all ultraviolet light/hydrogen peroxide-treated whirlpools tested positive for the presence of mycobacteria. No mycobacteria were detected in the chlorine-treated pools and the water main supply facility. All air samples collected in the proximity of the indoor whirlpools and the associated changing rooms were strongly positive for airborne mycobacteria. The airborne mycobacteria particles were predominantly collected on MOUDI stages 1-6 representing an aerodynamic size range of 0.5 to 9.9 microm. In conclusion, using this approach permits the rapid detection of mycobacteria contamination as well as the routine monitoring of suspected pools. The approach circumvents problems associated with culture-based methods such as fungal overgrowth on agar plates, and the presence of nonculturable or difficult to culture mycobacteria strains.