8 research outputs found
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
Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.
OBJECTIVE: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation
AngiotensinâConverting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVIDâ19
Background Use of angiotensinâconverting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) is thought to affect COVIDâ19 through modulating levels of angiotensinâconverting enzyme 2, the cell entry receptor for SARSâCoV2. We sought to assess the association between ACEi/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVIDâ19. Methods and Results We leveraged the ISIC (International Study of Inflammation in COVIDâ19), identified patients admitted for symptomatic COVIDâ19 between February 1, 2020 and June 1, 2021 for COVIDâ19, and examined the association between inâhospital ACEi/ARB use and allâcause 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 COVIDâ19. 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 Câreactive protein. In multivariable analysis, inâhospital ACEi/ARB use was associated with a lower risk of the composite outcome of inâhospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36â0.65]). Conclusions In patients hospitalized for COVIDâ19, ACEi/ARB use was associated with lower levels of inflammation and lower risk of inâhospital outcomes. Clinical trials will define the role of ACEi/ARB in the treatment of COVIDâ19. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866
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-19ârelated 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 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
Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVIDâ19
Background Venous thromboembolism (VTE) contributes significantly to COVIDâ19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVIDâ19. Whether suPAR levels identify patients with COVIDâ19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVIDâ19 with suPAR and Dâdimer levels measured on admission. In 1960 patients (mean age, 58âyears; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and FineâGray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and Dâdimer levels. There was a positive association between suPAR and Dâdimer (ÎČ=7.34; P=0.002). Adjusted for clinical covariables, including Dâdimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51â4.75]; P<0.001). Findings were consistent when stratified by Dâdimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined Dâdimer <1âmg/L and suPAR <11âng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of Dâdimer in patients hospitalized for COVIDâ19. Combining suPAR and Dâdimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866
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Obesity, inflammatory and thrombotic markers, and major clinical outcomes in critically ill patients with COVIDâ19 in the US
Objective
This study aimed to determine whether obesity is independently associated with major adverse clinical outcomes and inflammatory and thrombotic markers in critically ill patients with COVIDâ19.
Methods
The primary outcome was inâhospital mortality in adults with COVIDâ19 admitted to intensive care units across the US. Secondary outcomes were acute respiratory distress syndrome (ARDS), acute kidney injury requiring renal replacement therapy (AKIâRRT), thrombotic events, and seven blood markers of inflammation and thrombosis. Unadjusted and multivariableâadjusted models were used.
Results
Among the 4,908 study patients, mean (SD) age was 60.9 (14.7) years, 3,095 (62.8%) were male, and 2,552 (52.0%) had obesity. In multivariable models, BMI was not associated with mortality. Higher BMI beginning at 25 kg/m2 was associated with a greater risk of ARDS and AKIâRRT but not thrombosis. There was no clinically significant association between BMI and inflammatory or thrombotic markers.
Conclusions
In critically ill patients with COVIDâ19, higher BMI was not associated with death or thrombotic events but was associated with a greater risk of ARDS and AKIâRRT. The lack of an association between BMI and circulating biomarkers calls into question the paradigm that obesity contributes to poor outcomes in critically ill patients with COVIDâ19 by upregulating systemic inflammatory and prothrombotic pathways