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Background: Solid organ transplant (SOT) recipients are at risk of complications from COVID-19. Nirmatrelvir/ritonavir (Paxlovid) can reduce mortality from COVID-19 but is contraindicated in patients receiving calcineurin inhibitors (CI), which depend on cytochrome p4503A (CY3PA). In this study, we aim to show the feasibility of nirmatrelvir/ritonavir administration to SOT recipients receiving CI with coordination of medication management and limited tacrolimus trough monitoring., Methods: We reviewed adult SOT recipients treated with nirmatrelvir/ritonavir from 4/14 to 11/1/2022 and assessed for changes in tacrolimus trough and serum creatinine after therapy., Results: Of 47 patients identified, 28 were receiving tacrolimus and had follow-up laboratory testing. Patients had a mean age of 55 years, 17 (61%) received a kidney transplant and 23 (82%) received three or more doses of SARS-CoV-2 mRNA vaccine. Patients had mild-moderate COVID-19 and started nirmatrelvir/ritonavir within 5 days of symptom onset. Median baseline tacrolimus trough concentration was 5.6 ng/mL (Interquartile range 5.1-6.7), while median follow-up tacrolimus trough concentration was 7.8 ng/mL (Interquartile range 5.7-11.5, p = 0.0017). Median baseline and follow-up serum creatinine levels were 1.21 mg/dL (Interquartile range 1.02-1.39) and 1.21 mg/dL (interquartile range 1.02-1.44, p = 0.3162), respectively. One kidney recipient had a follow up creatinine level >1.5 times baseline. No patients were hospitalized or died from COVID-19 in the follow up period., Conclusion: While administration of nirmatrelvir/ritonavir resulted in a significant increase in tacrolimus concentration, this did not result in significant nephrotoxicity. Early oral antiviral treatment in SOT recipients is feasible with medication management, even with limited tacrolimus trough monitoring., (© 2023 Wiley Periodicals LLC.)

Context: The COVID-19 pandemic has highlighted variability in intensity of care. We aimed to characterize intensity of care among hospitalized patients with COVID-19., Objectives: Examine the prevalence and predictors of admission code status, palliative care consultation, comfort-measures-only orders, and cardiopulmonary resuscitation (CPR) among patients hospitalized with COVID-19., Methods: This cross-sectional study examined data from an international registry of hospitalized patients with COVID-19. A proportional odds model evaluated predictors of more aggressive code status (i.e., Full Code) vs. less (i.e., Do Not Resuscitate, DNR). Among decedents, logistic regression was used to identify predictors of palliative care consultation, comfort measures only, and CPR at time of death., Results: We included 29,923 patients across 179 sites. Among those with admission code status documented, Full Code was selected by 90% (n = 15,273). Adjusting for site, Full Code was more likely for patients who were of Black or Asian race (ORs 1.82, 95% CIs 1.5-2.19; 1.78, 1.15-3.09 respectively, relative to White race), Hispanic ethnicity (OR 1.89, CI 1.35-2.32), and male sex (OR 1.16, CI 1.0-1.33). Of the 4951 decedents, 29% received palliative care consultation, 59% transitioned to comfort measures only, and 29% received CPR, with non-White racial and ethnic groups less likely to receive comfort measures only and more likely to receive CPR., Conclusion: In this international cohort of patients with COVID-19, Full Code was the initial code status in the majority, and more likely among patients who were Black or Asian race, Hispanic ethnicity or male. These results provide direction for future studies to improve these disparities in care., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Rationale: The impact of palliative care consultation on end-of-life care has not previously been evaluated in a multi-center study., Objectives: To evaluate the impact of palliative care consultation on the incidence of cardiopulmonary resuscitation (CPR) performed and comfort care received at the end-of-life in hospitalized patients with COVID-19., Methods: We used the Society of Critical Care Medicine's COVID-19 registry to extract clinical data on patients hospitalized with COVID-19 between March 31st, 2020 to March 17th, 2021 and died during their hospitalization. The proportion of patients who received palliative care consultation was assessed in patients who did and did not receive CPR (primary outcome) and comfort care (secondary outcome). Propensity matching was used to account for potential confounding variables., Measurements and Main Results: 3,227 patients were included in the analysis. There was no significant difference in the incidence of palliative care consultation between the CPR and no-CPR groups (19.9% vs. 19.4%, p = 0.8334). Patients who received comfort care at the end-of-life were significantly more likely to have received palliative care consultation (43.3% vs. 7.7%, p < 0.0001). After propensity matching for comfort care on demographic characteristics and comorbidities, this relationship was still significant (43.2% vs. 8.5%; p < 0.0001)., Conclusion: Palliative care consultation was not associated with CPR performed at the end-of-life but was associated with increased incidence of comfort care being utilized. These results suggest that utilizing palliative care consultation at the end-of-life may better align the needs and values of patients with the care they receive., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Kumar is currently funded by funding the Gordon and Betty Moore Foundation, Centers for Disease Control and Prevention Foundation through the University of Washington, and Janssen Research & Development, LLC. Dr. Kashyap receives funding from the NIH/National Heart, Lung and Blood Institute: R01HL 130881, UG3/UH3HL 141722; Gordon and Betty Moore Foundation and Janssen Research & Development, LLC; and royalties from Ambient Clinical Analytics. Inc. Dr. Gajic receives funding from the Agency of Healthcare Research and Quality R18HS 26609-2, NIH/National Heart, Lung and Blood Institute: R01HL 130881, UG3/UH3HL 141722; Department of Defense DOD W81XWH; American Heart Association Rapid Response Grant—COVID-19; and royalties from Ambient Clinical Analytics. Inc. Dr. Walkey currently receives funding from the NIH/National Heart, Lung and Blood Institute grants R01HL151607, R01HL139751, R01HL136660, Agency of Healthcare Research and Quality, R01HS026485, Boston Biomedical Innovation Center/NIH/NHLBI 5U54HL119145-07, and royalties from UpToDate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome., Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19., Design, Setting, and Participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021., Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia., Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS)., Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001)., Conclusions and Relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present.

Background: Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population., Methods: We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19., Results: Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary artery disease (26%), and chronic obstructive pulmonary disease (14%). Twenty patients had severe COVID-19 (34.5%) and 38 had nonsevere disease (65.5%). Severe disease was more common in older SOT recipients with comorbidities and was associated with cough, dyspnea, pneumonia, C-reactive protein >10 mg/L, and platelet count <150/μL. Sex, race, body mass index, time from transplant, baseline immunosuppression, and diagnosis month did not differ among those with severe and nonsevere COVID-19. Seventy percent of SOT recipients were hospitalized vs 27.2% of general patients with COVID-19 and inpatient SOT recipients had a higher mechanical ventilation rate. Though a trend toward longer length of stay, higher intensive care unit admission, and greater inpatient mortality was observed (19.5% vs 14.8%), these differences were not significant., Conclusions: The severe acute respiratory syndrome coronavirus 2 has greatly impacted SOT recipients. One-third of our SOT recipients seen during the first wave had severe illness with associated standard risk factors for poor outcome. Compared with general first-wave patients, more SOT recipients were hospitalized, although inpatient COVID-19 mortality did not significantly differ., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. Methods: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. Results: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. Conclusion: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. Trial Registration Number: NCT04427501. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed SARS-CoV-2 vaccination antibody responses In a cohort of 273 patients with lymphoproliferative disorders or plasma cell dyscrasias who were seen at a single tertiary cancer center. Semi-quantitative anti-spike protein serologic testing was performed with enzyme immunoassay method. We found that the antibody response rate to SARS-CoV-2 vaccination was 74.7% in our patient cohort with no difference based on gender, age or race. The highest response rate was found in patients with Multiple Myeloma (MM) (95.5%). The response rates found in Diffuse Large B-Cell Lymphoma (DLBCL), Chronic Lymphocytic Leukemia (CLL), and Low-Grade Non-Hodgkin Lymphoma (LG-NHL) were 73.2%, 61.5% and 53% respectively. We also evaluated the effects of receiving active chemo-immunotherapy on SARS-CoV-2 vaccination antibody response. We found that the patients on treatment had lower response than the patients off treatment (62.1% versus 84.4% p<0.001). Thirty-four of 58 LG-NHL patients were receiving anti-lymphoma treatment with a lower SARS-CoV-2 vaccination response as compared to the patients who were not on treatment (29.4% v 87.5% p<0.001). We observed a similar pattern in CLL patients receiving treatment (48.1 v 76.0 p:0.049). We found that only disease type and treatment status (on-treatment vs. off-treatment), but not gender, age or race were significant predictors of non-response in the multivariable logistic regression model. The interaction between disease type and treatment status was not statistically significant by multivariate analysis. In conclusion, receiving anti-cancer treatment was found to play a significant role in decreasing the response to COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients. [ABSTRACT FROM AUTHOR]

B Introduction: b The severity of COVID-19 may be affected by environmental factors. While considering the altitude level, we found that it had a non-linear relationship with 28-day mortality (p=0.001, odds ratios for altitudes 75, 125, 400, and 600 m.a.s.l were: 0.96, 1.04, 0.49, and 0.51, respectively). [Extracted from the article]

B Conclusions: b MetS, diagnosed by the clustering of obesity, prediabetes/DM, HTN, and dyslipidemia, is associated with significantly increased mortality and ARDS in a global population of hospitalized COVID-19 patients. B Introduction/Hypothesis: b Little is known about metabolic syndrome (MetS) and ARDS in COVID-19. However, patients from non-US hospitals had significantly higher hospital mortality as compared with US hospitals (24.5% vs 15.7%, aOR 1.58 [CI 1.41-1.77]) with similar findings noted when patients were stratified by MetS (34.1% vs 21.3%, aOR 1.49 [CI 1.08-2.06]). [Extracted from the article]