Type I interferon autoantibodies in patients with COVID-19 are associated with poor interferon responses and increased LAIR1 abundance in leukocytes.

Rationale: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. Objectives: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. Methods: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case–control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively. Measurements and Main Results: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24–33%) and 10% based on the SPPB (95% CI, 7–14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01–1.67) for FFP and 1.53 (95% CI, 1.19–1.59) for SPPB. Conclusions: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

Healthcare systems worldwide are responding to Coronavirus Disease 2019 (COVID-19), an emerging infectious syndrome caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. Patients with COVID-19 can progress from asymptomatic or mild illness to hypoxemic respiratory failure or multisystem organ failure, necessitating intubation and intensive care management. Healthcare providers, and particularly anesthesiologists, are at the frontline of this epidemic, and they need to be aware of the best available evidence to guide therapeutic management of patients with COVID-19 and to keep themselves safe while doing so. Here, the authors review COVID-19 pathogenesis, presentation, diagnosis, and potential therapeutics, with a focus on management of COVID-19–associated respiratory failure. The authors draw on literature from other viral epidemics, treatment of acute respiratory distress syndrome, and recent publications on COVID-19, as well as guidelines from major health organizations. This review provides a comprehensive summary of the evidence currently available to guide management of critically ill patients with COVID-19.

Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score–adjusted Cox models. We calculated postestimation marginalized standardized risks for 1‐year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1‐ and 4‐year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6‐36.0 and aHR 3.8; 95%CI: 1.8‐8.0, respectively). Each 1‐point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08‐1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%‐21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1‐13.2) but not over longer follow‐up. Preoperative frailty is associated with an increased risk of death after lung transplantation.

Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet production and phenotypes of resultant platelets. Here, we showed during sepsis that the spleen was a major site of megakaryopoiesis and platelet production. Sepsis provoked an adrenergic-dependent mobilization of megakaryocyte-erythrocyte progenitors (MEPs) from the bone marrow to the spleen, where IL-3 induced their differentiation into megakaryocytes (MKs). In the spleen, immune-skewed MKs produced a CD40 ligand^hi platelet population with potent immunomodulatory functions. Transfusions of post-sepsis platelets enriched from splenic production enhanced immune responses and reduced overall mortality in sepsis-challenged animals. These findings identify a spleen-derived protective platelet population that may be broadly immunomodulatory in acute inflammatory states such as sepsis.