IMPORTANCE During the coronavirus disease 2019 pandemic, there may be too few ventilators to meet medical demands. It is unknown how many US states have ventilator allocation guidelines and how these state guidelines compare with one another. OBJECTIVE To evaluate the number of publicly available US state guidelines for ventilator allocation and the variation in state recommendations for how ventilator allocation decisions should occur and to assess whether unique criteria exist for pediatric patients. EVIDENCE REVIEW This systematic review evaluated publicly available guidelines about ventilator allocation for all states in the US and in the District of Columbia using department of health websites for each state and internet searches. Documents with any discussion of a process to triage mechanical ventilatory support during a public health emergency were screened for inclusion. Articles were excluded if they did not include specific ventilator allocation recommendations, were in draft status, did not include their state department of health, or were not the most up-to-date guideline. All documents were individually assessed and reassessed by 2 independent reviewers from March 30 to April 2 and May 8 to 10, 2020. FINDINGS As of May 10, 2020, 26 states had publicly available ventilator guidelines, and 14 states had pediatric guidelines. Use of the Sequential Organ Failure Assessment score in the initial rank of adult patients was recommended in 15 state guidelines (58%), and assessment of limited life expectancy from underlying conditions or comorbidities was included in 6 state guidelines (23%). Priority was recommended for specific groups in the initial evaluation of patients in 6 states (23%) (ie, Illinois, Maryland, Massachusetts, Michigan, Pennsylvania, and Utah). Many states recommended exclusion criteria in adult (11 of 26 states [42%]) and pediatric (10 of 14 states [71%]) ventilator allocation. Withdrawal of mechanical ventilation from a patient to give to another if a shortage occurs was discussed in 22 of 26 adult guidelines (85%) and 9 of 14 pediatric guidelines (64%). CONCLUSIONS AND RELEVANCE These findings suggest that although allocation guidelines for mechanical ventilatory support are essential in a public health emergency, only 26 US states provided public guidance on how this allocation should occur. Guidelines among states, including adjacent states, varied significantly and could cause inequity in the allocation of mechanical ventilatory support during a public health emergency, such as the coronavirus disease 2019 pandemic.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike. IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.

IMPORTANCE Crisis Standards of Care (CSC) are guidelines for rationing health care resources during public health emergencies. The CSC adopted by US states ration intensive care unit (ICU) admission using the Sequential Organ Failure Assessment (SOFA) score, which is used to compare expected in-hospital mortality among eligible patients. However, it is unknown if Black and White patients with equivalent SOFA scores have equivalent in-hospital mortality.OBJECTIVE To investigate whether reliance on SOFA is associated with bias against Black patients in CSC. DESIGN, SETTING, AND PARTICIPANTSThis cohort study was conducted using data from the eICU Collaborative Research Database of patients admitted to 233 US ICUs in 2014 to 2015. Included individuals were Black and White adult patients in the ICU, who were followed up to hospital discharge. Data were analyzed from May 2020 through April 2021.EXPOSURE SOFA scores at ICU admission. MAIN OUTCOMES AND MEASURESHierarchical logistic regression with hospital fixed effects was used to measure the interaction between race and SOFA as a factor associated with in-hospital mortality, as well as the odds of death among Black and White patients with equivalent priority for resource allocation according to the SOFA-based ranking rules of 3 statewide CSC (denoted A, B, and C) under shortage conditions that were severe (ie, only patients with the highest priority would be eligible for allocation), intermediate (ie, patients in the highest 2 tiers would be eligible for allocation), or low (ie, only patients with the lowest priority would be at risk of exclusion). RESULTS Among 111 885 ICU encounters representing 95 549 patients, there were 16 688 encounters with Black patients (14.9%) and 51 464 (46.0%) encounters with women and the mean (SD) age was 63.3 (16.9) years. The median (interquartile range) SOFA score was not statistically significantly different between Black and White patients (4 [2-6] for both groups; P = .19), but mortality was lower among Black individuals compared with White individuals with equivalent SOFA scores (odds ratio [OR], 0.98; 95% CI, 0.97-0.99; P < .001). This was associated with lower mortality among Black patients compared with White patients prioritized for resource allocation in 3 CSC under shortage conditions that were severe

Although sepsis has been characterized as a dysregulated immune response to an ongoing or suspected infection, the role of the microbiome as a key influencer of the septic response is emerging. The unavoidable disruption of the microbiome while treating sepsis with antibiotics can itself result in immune system dysregulation, further exacerbating the course and outcome of sepsis. Alterations in the gut microbiome as a result of sepsis and its treatment have been implicated in the organ dysfunction typical of sepsis across a wide variety of tissues including the lung, kidney and brain. A number of microbiota directed interventions are currently under investigation in the setting of sepsis including fecal transplant, the administration of dietary fiber in enteral feeding products and the use of antibiotic scavengers that are directed at attenuating the effects of antibiotics on the gut microbiota while allowing them to concentrate at the primary sites of infection. Taken together, the emerging role of the gut microbiome in sepsis touches various elements of the pathophysiology of sepsis and its treatment, and provides yet another reason to consider the judicious use of antibiotics via antibiotic stewardship programs.

Described herein is the development of a control strategy resulting in exclusion of a persistent impurity (6) formed by a palladium (II)-mediated homocoupling of boronic acid (3) during a Suzuki cross-coupling reaction. Nearly complete suppression of the undesired homocoupling reaction was achieved through two process modifications. Thus, addition of a mild reducing agent, potassium formate, and use of a facile nitrogen subsurface sparge prior to introduction of the catalyst resulted in nearly complete exclusion of homocoupling dimer 6. These modifications apparently minimized the concentration of free Pd(II) in the reaction mixture without causing significant reduction of the oxidative addition product. In addition, use of palladium black as a heterogeneous coupling catalyst rendered the palladium control strategy trivial. Thus, the catalyst was separated from the product solution through use a clarifying filtration, resulting in near quantitative separation of palladium from LY 451395 (5). These conditions were successfully executed in three campaigns using 3-, 5-, 12-, and 22-L glassware.