SuPAR, biomarkers of inflammation, and severe outcomes in patients hospitalized for COVID-19: The International Study of Inflammation in COVID-19.

Severe coronavirus disease 2019 (COVID-19) is a hyperinflammatory syndrome. The biomarkers of inflammation best suited to triage patients with COVID-19 are unknown. We conducted a prospective multicenter observational study of adult patients hospitalized specifically for COVID-19 from February 1, 2020 to October 19, 2022. Biomarkers measured included soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, interleukin-6, procalcitonin, ferritin, and D-dimer. In-hospital outcomes examined include death and the need for mechanical ventilation. Patients admitted in the United States (US, n = 1962) were used to compute area under the curves (AUCs) and identify biomarker cutoffs. The combined European cohorts (n = 1137) were used to validate the biomarker cutoffs. In the US cohort, 356 patients met the composite outcome of death (n = 197) or need for mechanical ventilation (n = 290). SuPAR was the most important predictor of the composite outcome and had the highest AUC (0.712) followed by CRP (0.642), ferritin (0.619), IL-6 (0.614), D-dimer (0.606), and lastly procalcitonin (0.596). Inclusion of other biomarkers did not improve discrimination. A suPAR cutoff of 4.0 ng/mL demonstrated a sensitivity of 95.4% (95% CI: 92.4%-98.0%) and negative predictive value (NPV) of 92.5% (95% CI: 87.5%-96.9%) for the composite outcome. Patients with suPAR < 4.0 ng/mL comprised 10.6% of the cohort and had a 0.8% probability of the composite outcome. Applying this cutoff to the validation cohort yielded a sensitivity of 93.8% (90.4%-96.7%) and NPV of 95.5% (93.1%-97.8%) for the composite outcome. Among commonly measured biomarkers, suPAR offered stronger discriminatory ability and may be useful in triaging low-risk patients with COVID-19.

Differences in Inflammation, Treatment, and Outcomes Between Black and Non-Black Patients Hospitalized for COVID-19: A Prospective Cohort Study.

PURPOSE: Racial disparities in coronavirus disease 2019 (COVID-19) outcomes have been described. We sought to determine whether differences in inflammatory markers, use of COVID-19 therapies, enrollment in clinical trials, and in-hospital outcomes contribute to racial disparities between Black and non-Black patients hospitalized for COVID-19. METHODS: We leveraged a prospective cohort study that enrolled 1325 consecutive patients hospitalized for COVID-19, of whom 341 (25.7%) were Black. We measured biomarkers of inflammation and collected data on the use COVID-19-directed therapies, enrollment in COVID-19 clinical trials, mortality, need for renal replacement therapy, and need for mechanical ventilation. RESULTS: Compared to non-Black patients, Black patients had a higher prevalence of COVID-19 risk factors including obesity, hypertension, and diabetes mellitus and were more likely to require renal replacement therapy (15.8% vs 7.1%, P < .001) and mechanical ventilation (37.2% vs 26.6%, P < .001) during their hospitalization. Mortality was similar between both groups (15.5% for Blacks vs 14.0% for non-Blacks, P = .49). Black patients were less likely to receive corticosteroids (44.9% vs 63.8%, P< .001) or remdesivir (23.8% vs 57.8%, P < .001) and were less likely to be enrolled in COVID-19 clinical trials (15.3% vs 28.2%, P < .001). In adjusted analyses, Black race was associated with lower levels of C-reactive protein and soluble urokinase receptor and higher odds of death, mechanical ventilation, and renal replacement therapy. Differences in outcomes were not significant after adjusting for use of remdesivir and corticosteroids. CONCLUSIONS: Racial differences in outcomes of patients with COVID-19 may be related to differences in inflammatory response and differential use of therapies.

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID-19.

Background Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) is thought to affect COVID-19 through modulating levels of angiotensin-converting enzyme 2, the cell entry receptor for SARS-CoV2. We sought to assess the association between ACEi/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVID-19. Methods and Results We leveraged the ISIC (International Study of Inflammation in COVID-19), identified patients admitted for symptomatic COVID-19 between February 1, 2020 and June 1, 2021 for COVID-19, and examined the association between in-hospital ACEi/ARB use and all-cause death, need for ventilation, and need for dialysis. We estimated the causal effect of ACEi/ARB on the composite outcomes using marginal structural models accounting for serial blood pressure and serum creatinine measures. Of 2044 patients in ISIC, 1686 patients met inclusion criteria, of whom 398 (23.6%) patients who were previously on ACEi/ARB received at least 1 dose during their hospitalization for COVID-19. There were 215 deaths, 407 patients requiring mechanical ventilation, and 124 patients who required dialysis during their hospitalization. Prior ACEi/ARB use was associated with lower levels of soluble urokinase plasminogen activator receptor and C-reactive protein. In multivariable analysis, in-hospital ACEi/ARB use was associated with a lower risk of the composite outcome of in-hospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36-0.65]). Conclusions In patients hospitalized for COVID-19, ACEi/ARB use was associated with lower levels of inflammation and lower risk of in-hospital outcomes. Clinical trials will define the role of ACEi/ARB in the treatment of COVID-19. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

In-hospital cardiac arrest in critically ill patients with covid-19: multicenter cohort study.

OBJECTIVES: To estimate the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and cardiopulmonary resuscitation in critically ill adults with coronavirus disease 2019 (covid-19). DESIGN: Multicenter cohort study. SETTING: Intensive care units at 68 geographically diverse hospitals across the United States. PARTICIPANTS: Critically ill adults (age ≥18 years) with laboratory confirmed covid-19. MAIN OUTCOME MEASURES: In-hospital cardiac arrest within 14 days of admission to an intensive care unit and in-hospital mortality. RESULTS: Among 5019 critically ill patients with covid-19, 14.0% (701/5019) had in-hospital cardiac arrest, 57.1% (400/701) of whom received cardiopulmonary resuscitation. Patients who had in-hospital cardiac arrest were older (mean age 63 (standard deviation 14) v 60 (15) years), had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of intensive care unit beds compared with those who did not have in-hospital cardiac arrest. Patients who received cardiopulmonary resuscitation were younger than those who did not (mean age 61 (standard deviation 14) v 67 (14) years). The most common rhythms at the time of cardiopulmonary resuscitation were pulseless electrical activity (49.8%, 199/400) and asystole (23.8%, 95/400). 48 of the 400 patients (12.0%) who received cardiopulmonary resuscitation survived to hospital discharge, and only 7.0% (28/400) survived to hospital discharge with normal or mildly impaired neurological status. Survival to hospital discharge differed by age, with 21.2% (11/52) of patients younger than 45 years surviving compared with 2.9% (1/34) of those aged 80 or older. CONCLUSIONS: Cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival, particularly among older patients.

Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI.

BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.

Postoperative Complications of Ab Interno Gelatin Microstent.

PURPOSE: To report 4 previously undescribed postoperative complications in 4 cases of ab interno XEN45 Gel Stent (XEN) implantation following uncomplicated surgeries. PATIENTS AND METHODS: A total of 51 consecutive XEN implantations performed between July 1, 2017 and April 30, 2018 were reviewed. All cases were performed by 7 experienced glaucoma surgeons affiliated with the William Beaumont Hospital, Department of Ophthalmology. Cases with postoperative complications were identified, and a literature review was performed on PubMed.gov between April 5, 2018 and June 2, 2018 to identify previously unreported XEN complications. RESULTS: Case 1 consisted of an 86-year-old woman who suffered a suprachoroidal hemorrhage and associated rhegmatogenous retinal detachment following XEN implantation. One month after sclerotomy drainage and pars plana vitrectomy repair, an amputated XEN was found to have eroded through the conjunctiva. Case 2 consisted of a 68-year-old man with persistent elevated intraocular pressure due to recurrent Tenon's capsule fibrosis who developed complete XEN retraction into the subconjunctival space. Cases 3 and 4 consisted of a 68-year-old man and a 78-year-old woman who developed occlusion of the microstent's internal ostium by a partially detached Descemet's membrane. Case 3 maintained normal intraocular pressure on timolol, whereas case 4 resulted in bleb failure, despite Nd:YAG laser lysis of the occluded XEN internal ostium. CONCLUSIONS: Although the XEN is a promising new surgical option for the management of primary open-angle glaucoma, it can present unique postoperative challenges that are still being elucidated. Timely intervention or prevention of these complications can be improved by early surgeon recognition and effective communication with comanaging ophthalmologists.