Abhijit Duggal

Background: Human metapneumovirus (HMPV) is a significant cause of acute respiratory illness in both children and adults, yet its genomic epidemiology remains understudied compared to other respiratory viruses. Methods: Hybrid capture and whole-genome sequencing were performed on 616 HMPV-positive specimens from 2 cohorts: the household-based HIVE study (2010–2022) in Michigan and the multicenter IVY network (2022–2025) of hospitalized adults. Consensus sequences were generated using IRMA, clades were annotated using Nextclade, and phylogenetic trees were constructed separately for HMPV-A and HMPV-B using IQ-TREE and TreeTime. Analysis of selection by dN/dS was performed using SLAC. Results: We obtained complete genomes from 325 specimens. Our analyses revealed the continued predominance of the A2.2.2 clade and little geographic structure in the United States. Genomic diversity was highest in the glycoprotein (G); we identified a shift from variants bearing the 180nt duplication to ones with a 111nt duplication. Phylogenetic analyses supported the duplication-deletion model for the origin of the duplications. The conserved fusion (F) protein showed limited antigenic variation and low rates of nonsynonymous substitutions Conclusions: These findings underscore the utility of enhanced genomic surveillance for understanding HMPV evolution and informing vaccine development. There was little genomic diversity in vaccine-targeted epitopes.

Human metapneumovirus (HMPV) is a significant cause of acute respiratory illness in both children and adults, yet its genomic epidemiology remains understudied compared to other respiratory viruses. Here, we report an expanded genomic surveillance of HMPV in the United States, utilizing 325 newly sequenced samples from two cohorts: the household-based HIVE study (2010–2022) in Michigan and the multicenter IVY network (2022–2025) of hospitalized adults. Our analyses revealed the continued predominance of the A2.2.2 clade and little geographic structure in the US. Genomic diversity is highest in the glycoprotein (G); we identified a shift from variants bearing the 180nt duplication to ones with a 111nt duplication. Phylogenetic analyses supported the duplication-deletion model for the origin of the duplications. The conserved fusion (F) protein shows limited antigenic variation and low rates of nonsynonymous substitutions, suggesting stability in epitopes targeted by vaccine candidates. These findings underscore the utility of enhanced genomic surveillance for understanding HMPV evolution and informing vaccine development. Summary: Genomic surveillance of HMPV in the United States over a 15 year period reveals extensive genetic diversity and more rapid evolution in the G protein compared to the F protein, which is targeted by vaccines under development.

The definition of acute respiratory distress syndrome (ARDS) has been updated several times since the syndrome was first described in 1967. The aim of the initial definition was to better study this disease and standardize its care. Each iteration has brought its own set of nuances and challenges. In 2024, a new global definition of ARDS was proposed. This review highlights the evolution of ARDS definitions over the years and discusses the key components of the new proposed global definition.

IMPORTANCE: Vasopressin is used in one-third of patients with septic shock to augment hemodynamics and reduce overall catecholamine exposure. However, the optimal clinical context in which to initiate vasopressin is unknown. OBJECTIVES: To determine the association between norepinephrine-equivalent dose, lactate concentration, and time duration from shock onset at vasopressin initiation with in-hospital mortality DESIGN, SETTING, AND PARTICIPANTS: Retrospective, observational evaluation utilizing Medical Information Mart for Intensive Care-IV and electronic ICU Collaborative Research Database databases of adult patients with septic shock based on modified Sepsis-3 criteria receiving continuous infusion catecholamines. MAIN OUTCOMES AND MEASURES: The associations of norepinephrine-equivalent dose, lactate concentration, and time duration from shock onset at vasopressin initiation with in-hospital mortality were evaluated with multivariable regression models. RESULTS: In total, 1409 patients from 209 hospitals were included. At vasopressin initiation patients had a median (interquartile range) norepinephrine-equivalent dose 28.4 µg/min (16.4–42.6 µg/min), lactate concentration 3.7 mmol/L (2.5–6.2 mmol/L), and 5.6 hours (2.0–13.5 hr) had elapsed since shock onset. All three variables of interest were associated with in-hospital mortality. Three restricted cubic spline knots were identified where the relationship between norepinephrine-equivalent dose and in-hospital mortality changed substantially: 9, 28, and 72 µg/min. The odds of in-hospital mortality increased by 90% and 3.9-fold when comparing vasopressin initiation at norepinephrine-equivalent doses of 28 µg/min and 72 µg/min to 9 µg/min, respectively (adjusted odds ratio [OR], 1.90 [95% CI, 1.49–2.41] and 3.93 [95% CI, 2.74–5.64]). The odds of in-hospital mortality increased by 16% for every mmol/L in the lactate concentration at vasopressin initiation (adjusted OR, 1.16 [95% CI, 1.11–1.21]). Finally, the odds of in-hospital mortality increased by 3% for every hour in the time duration from shock onset to vasopressin initiation (adjusted OR, 1.03 [95% CI, 1.01–1.04]). CONCLUSIONS AND RELEVANCE: Earlier adjunctive vasopressin initiation may decrease mortality in patients with septic shock.

IMPORTANCE: Receipt of fluid and vasopressors, common treatments in septic shock, may affect cardiac function. OBJECTIVES: We sought to determine whether a liberal or restrictive fluid resuscitation strategy was associated with changes in cardiac function. DESIGN: We prospectively studied a subset of patients enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial, performing echocardiography at baseline and at 24 hours after randomization. Among patients who had an echocardiogram performed at 24 hours, we measured left ventricular global longitudinal strain (LV GLS) and right ventricular free-wall longitudinal strain (RVFWLS). We performed linear regressions with dependent variables of LV GLS, change in LV GLS (ΔLV GLS), and RVFWLS using treatment assignment as an independent variable. We adjusted for ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity, mean arterial pressure, and history of congestive heart failure and myocardial infarction. SETTING: Emergency department and ICUs. PATIENTS: Adults with sepsis enrolled in the CLOVERS trial. MAIN OUTCOMES AND MEASURES: We enrolled 180 patients. Our analytic cohort comprised 131 patients with an echocardiogram performed at 24 hours. We observed no differences between treatment arms with respect to demographic, clinical, or echocardiographic data at baseline. We observed no association between restrictive fluid assignment and LV GLS (coefficient, 1.22; p = 0.23), ΔLV GLS (–1.97; p = 0.27), or RVFWLS (2.33; p = 0.19). CONCLUSIONS AND RELEVANCE: In a subset of patients enrolled in CLOVERS, we observed no association between receipt of fluid and vasopressors and short-term changes in cardiac function. Decreased enrollment may limit inferences.