Objective: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic. Methods: We conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19. Results: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twentythree of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group). Conclusions: Implementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises.

The liver is an organ that, when dysfunctional in a septic patient, is strongly associated with morbidity and mortality. Understanding the pathophysiology of liver failure during sepsis may lead to improved diagnostics and potential therapeutic targets. Historically, programmed cell death receptor (PD) ligand 1 (PD-L1) has been considered the primary ligand for its checkpoint molecule counterpart, PD-1, with PD-L2 rarely in the immunopathological spotlight. PD-1 and PD-L1 contribute to liver dysfunction in a murine cecal ligation and puncture (CLP) model of sepsis, but virtually nothing is known about PD-L2’s role in sepsis. Therefore, our central hypothesis was that sepsis-induced changes in hepatic PD-L2 expression contributed to worsened liver function and, subsequently, more pronounced morbidity and mortality. We found that although PD-L1 gene deficiency attenuated the hepatic dysfunction seen in wild-type mice after CLP, the loss of PD-L2 appeared to actually worsen indices of liver function along with a trend toward higher liver tissue vascular permeability. Conversely, some protective effects of PD-L2 gene deletion were noted, such as reduced liver/peritoneal bacterial load and reduced IL-6, IL-10, and macrophage inflammatory protein 2 levels following CLP. These diverse actions, as well as the unique expression pattern of PD-L2, may explain why no overt survival advantage could be witnessed in the septic PD-L2−/− mice. Taken together, these data suggest that although PD-L2 has some selective effects on the hepatic response seen in the septic mouse, these factors are not sufficient to alter septic mortality in this adult murine model. NEW & NOTEWORTHY Our study shows not only that ligands of the checkpoint protein PD-1 respond inversely to a stressor such as septic challenge (PD-L2 declines, whereas PD-L1 rises) but also that aspects of liver dysfunction increase in septic mice lacking the PD-L2 gene. Furthermore, these differences in PD-L2 gene-deficient animals culminated in the abrogation of the survival advantage seen in the septic PD-L1-knockout mice, suggesting that PD-L2 may have roles beyond a simple immune tolerogen.

Sepsis remains a major public health concern, characterized by marked immune dysfunction. Innate lymphoid cells develop from a common lymphoid precursor but have a role in orchestrating inflammation during innate response to infection. Here, we investigate the pathologic contribution of the group 2 innate lymphoid cells (ILC2s) in a murine model of acute septic shock (cecal ligation and puncture). Flow cytometric data revealed that ILC2s increase in number and percentage in the small intestine and in the peritoneal cells and inversely decline in the liver at 24 hours after septic insult. Sepsis also resulted in changes in ILC2 effector cytokine (IL-13) and activating cytokine (IL-33) in the plasma of mice and human patients in septic shock. Of interest, the sepsis-induced changes in cytokines were abrogated in mice deficient in functionally invariant natural killer T cells. Mice deficient in IL-13-producing cells, including ILC2s, had a survival advantage after sepsis along with decreased morphologic evidence of tissue injury and reduced IL-10 levels in the peritoneal fluid. Administration of a suppressor of tumorigenicity 2 (IL-33R) receptor-blocking antibody led to a transient survival advantage. Taken together, these findings suggest that ILC2s may play an unappreciated role in mediating the inflammatory response in both mice and humans; further, modulating ILC2 response in vivo may allow development of immunomodulatory strategies directed against sepsis.