IMPORTANCEThe psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined.OBJECTIVE To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission.DESIGN, SETTING, AND PARTICIPANTS This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states.EXPOSURE Having a family member in the ICU with COVID-19.MAIN OUTCOMES AND MEASURES Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). RESULTS A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients' child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P < .001) than male participants, whereas Hispanic participants scored a mean of 2.7 points higher compared with non-Hispanic participants (95% CI, 1.0-4.3; P = .002). Those with graduate school experience had an adjusted mean score of 3.3 points lower (95% CI, 1.5-5.1; P < .001) compared with those with up to a high school degree or equivalent. Qualitative analyses found no substantive differences in the emotional or communication-related experiences between those with high vs low PTSD scores, but those with higher scores exhibited more distrust of practitioners. CONCLUSIONS AND RELEVANCEIn this cohort study, symptoms of PTSD among family members of ICU patients with COVID-19 were high. Hispanic ethnicity and female gender were associated with higher symptoms. Those with higher scores reported more distrust of practitioners.

Objective This living systematic review aims to integrate the morphological and tissue-based molecular characterization of oral lesions occurring in individuals infected by COVID-19 (OLICs). Materials and Design This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Web of Science, Scopus, Ovid, Embase, and LILACS were searched to identify reports on OLICs with morphological and/or tissue-based molecular data. Results Four studies reporting five cases were included. Three patients were male, and the mean age of the individuals was 47.6 years. The most reported anatomical location was the palate (n = 4), whereas ulcers were the most frequent clinical presentation (n = 3). Histopathologically, all cases revealed cell vacuolization and exocytosis in the epithelial layer. In the mesenchymal layer, inflammatory cell infiltrate and thrombi/microvascular thrombosis were observed in three cases. Immunohistochemical reactions were performed in two cases. Both cases were negative for HHV-1, HHV-2, and CMV. One case revealed positivity for SARS-CoV-2 spike protein. No other molecular tests were found for the characterization of OLIC. Conclusions The pathological characteristics of OLICs are still unspecific. However, with the ongoing COVID-19 pandemic and well-documented new cases, whether OLICs are due to coinfections or has a primary origin can be determined.

Within medicine, there is a growing focus on understanding the care that is provided at the end of life (1). Although the ability to capture preferences for life-sustaining treatments in routinely collected healthcare data is limited, one existing option is the International Classification of Diseases, Ninth Revision (ICD-9), code V49.86, signifying "do-not-resuscitate status." This code may potentially be used to examine the care of patients with do-notresuscitate (DNR) status (2, 3); to examine trends, patterns, and variation in end-of-life decision making (4); or potentially to adjust for patient preferences when examining the quality of care (5). However, performance characteristics for this code are unknown. Therefore, we performed a single-center validation study to determine the sensitivity and specificity of the V49.86 code for identifying whether hospitalized patients had a DNR status at any time during their hospitalization. We hypothesized that the code would be specific but not sensitive for the presence of DNR status. MethodsThis study was approved by the Columbia University Medical Center (CUMC) Institutional Review Board (IRB-AAAP2112 New York, NY). Written informed consent was waived. Data for this study were extracted from the CUMC Clinical Data Warehouse, a repository of electronic medical records for all hospitalizations at CUMC. We included all adult admissions (age >18 yr) from August 1, 2013, through August 31, 2015, including repeat hospitalizations. We collected demographic and clinical variables, including age, sex, race, whether patients were admitted to an intensive care unit (ICU), discharge destination, and all diagnoses received during the hospitalization. Although our unit of analysis LETTERSAuthor disclosures are available with the text of this letter at www.atsjournals.org.

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ImportancePreclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology.ObjectiveTo evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor–biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II.Design, Setting, and ParticipantsTwo randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022.InterventionsA 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo.Main Outcomes and MeasuresThe primary outcome was oxygen-free days, an ordinal outcome that classifies a patient’s status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension.ResultsBoth trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, −2.3 [95% CrI, −4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, −2.4 [95% CrI, −5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo.Conclusions and RelevanceIn adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04924660

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Background Although use of mechanical circulatory support is increasing, it is unclear how providing such care affects clinicians’ moral distress. Objective To measure moral distress among intensive care unit clinicians who commonly care for patients receiving mechanical circulatory support. Methods In this prospective study, the Moral Distress Scale-Revised was administered to physicians, nurses, and advanced practice providers from 2 intensive care units in an academic medical center. Linear regression was used to assess whether moral distress was associated with clinician type, burnout, or desire to leave one’s job. Clinicians’ likelihood of reporting frequent moral distress when caring for patients receiving mechanical circulatory support vs other critically ill patients also was assessed. Results The sample comprised 102 clinicians who had a mean (SD) score of 100.5 (51.6) on the Moral Distress Scale- Revised. After adjustment for clinician characteristics, moral distress was significantly higher in registered nurses than physicians/advanced practice providers (115.9 vs 71.0, P &lt; .001), clinicians reporting burnout vs those who did not (114.7 vs 83.1, P = .003), and those considering leaving vs those who were not (121.1 vs 89.2, P = .001). Clinicians were more likely to report experiencing frequent moral distress when caring for patients receiving mechanical circulatory support (26.5%) than when caring for patients needing routine care (10.8%; P = .004), but less likely than when caring for patients with either chronic critical illness (57.8%) or multisystem organ failure (56.9%; both P &lt; .001). Conclusion Moral distress was high among clinicians who commonly care for patients receiving mechanical circulatory support, suggesting that use of this therapy may affect well-being among intensive care unit clinicians.

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