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BackgroundPatients receiving maintenance dialysis represent a high risk, immune-compromised population with 15-25% COVID mortality rate who were unrepresented in clinical trials evaluated for mRNA vaccines’ emergency use authorization.MethodAll patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021 were included. We report seroresponse based on levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive ≥2) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur® XP/XPT COV2G).ResultsAmong 186 dialysis patients from 32 clinics in 8 states tested 23±8 days after receiving 2 vaccine doses, mean age was 68±12 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer.ConclusionMost patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for eligible dialysis patients, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.SignificanceIn this retrospective observational evaluation of SARS-CoV-2 mRNA vaccine response defined by detectable levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen of ≥2 in serum of patients receiving maintenance dialysis, 165/186 (88.7%) were found to be seropositive (with 70% at maximum titer) at least 14 days after completing the second dose. No significant differences were observed by race or other subgroup or by vaccine manufacturer. Therefore, an equitable and aggressive vaccination strategy for all eligible maintenance dialysis patients, regardless of age, sex, race, ethnicity, or disability, is warranted to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.

Background The majority of dialysis patients receive aggressive burdensome treatment near the end of life. Currently, we lack interventions to improve end-of-life care (EoLC) for these patients. We examined the association of palliative care consultation with improving EoLC for critically ill patients with end-stage renal disease (ESRD) who received cardiopulmonary resuscitation (CPR). Materials and methods In this retrospective study, we included patients with ESRD admitted to a large academic center who received CPR either prior to or during their hospital stay. Over 8 years, 17 out of 403 patients received palliative care consultation during their hospital stay; consultations were not standardized in their content. Main outcomes of interest to operationalize better EoLC were: (1) change in code status from full code to do not resuscitate (DNR) and (2) withdrawal from intensive care. Results Of the patients studied, 60.5% were African-American and 43.2% were female. Demographic differences between those with palliative care consultation and those with usual care were not statistically significant. Palliative care consultation was associated with higher odds of change in code status to DNR (odds ratio 8.10, 95% confidence interval 2.19 - 29.94) and withdrawal from intensive care (odds ratio 8.82, 95% confidence interval 2.69 - 28.91) in patients with ESRD who had received CPR. Palliative care consultation was not associated with any change in in-hospital mortality. Conclusion Palliative care consultation needs to be considered for hospitalized ESRD patients with limited expected prognoses as it may reduce aggressive and burdensome therapies at the end of life. Furthermore, primary palliative care skills such as communication and decision-making should be taught to nephrologists to improve EoLC for dialysis patients.

Given the increased morbidity and mortality from COVID-19 among patients undergoing maintenance dialysis, we examined the seroresponse to an additional dose of SARS-CoV-2 mRNA vaccine, using a hypothesized protective anti-spike protein IgG antibody threshold of 7 based on prior work. Among 395 patients, 384 (97%) had seroresponse ≥7 following administration of the third dose. Among those with suboptimal (peak

Objective To determine whether surge conditions were associated with increased mortality. Design Multicenter cohort study. Setting U.S. ICUs participating in STOP-COVID. Patients Consecutive adults with COVID-19 admitted to participating ICUs between March 4 and July 1, 2020. Interventions None Measurements and Main Results The main outcome was 28-day in-hospital mortality. To assess the association between admission to an ICU during a surge period and mortality, we used two different strategies: (1) an inverse probability weighted difference-in-differences model limited to appropriately matched surge and non-surge patients and (2) a meta-regression of 50 multivariable difference-in-differences models (each based on sets of randomly matched surge- and non-surge hospitals). In the first analysis, we considered a single surge period for the cohort (March 23 – May 6). In the second, each surge hospital had its own surge period (which was compared to the same time periods in matched non-surge hospitals). Our cohort consisted of 4342 ICU patients (average age 60.8 [sd 14.8], 63.5% men) in 53 U.S. hospitals. Of these, 13 hospitals encountered surge conditions. In analysis 1, the increase in mortality seen during surge was not statistically significant (odds ratio [95% CI]: 1.30 [0.47-3.58], p = .6). In analysis 2, surge was associated with an increased odds of death (odds ratio 1.39 [95% CI, 1.34-1.43], p Conclusions Admission to an ICU with COVID-19 in a hospital that is experiencing surge conditions may be associated with an increased odds of death. Given the high incidence of COVID-19, such increases would translate into substantial excess mortality.

SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19 related hospitalization or death in the dialysis population is unknown.Retrospective, observational study.Adult patients receiving maintenance dialysis through a national dialysis provider without COVID-19 history treated between February 1, 2021 and December 18, 2021 with follow up through January 17, 2022.SARS-CoV-2 vaccination status.All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19.Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness.Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, while 891 (73%) cases occurring during the Delta period. Between pre-Delta period and Delta periods vaccine effectiveness against a severe COVID-19 related event (hospitalization or death) was 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike IgG assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and adjusted hazard ratios for both infection and COVID-related hospitalization or death.Observational design, residual biases and confounding may exist.Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, low anti-spike IgG level is associated with worse COVID-19 related outcomes.

BackgroundSARS-CoV-2 vaccine effectiveness during the Delta period and immunogenicity threshold associated with protection against COVID-19 related hospitalization or death in the dialysis population is unknown.MethodsA retrospective, observational study assessed SARS-CoV-2 vaccine effectiveness and immunogenicity threshold in all adult maintenance dialysis patients without COVID-19 history treated between February 1 and October 2, 2021. All COVID-19 infections, composite of hospitalization or death following COVID-19 and available SARS-CoV-2 anti-spike immunoglobulin (Ig) G values were extracted from electronic medical record. COVID-19 cases per 10,000 days at risk and vaccine effectiveness during pre-Delta and Delta periods were determined.ResultsOf 15,718 patients receiving dialysis during the study period, 11,191 (71%) were fully vaccinated, 733 (5%) were partially vaccinated and 3,794 (24%) were unvaccinated. 967 COVID-19 were cases identified: 511 (53%) occurred in unvaccinated patients and 579 (60%) occurred during the Delta period. COVID-19 related hospitalization or death was less likely among vaccinated versus unvaccinated patients for all vaccines (adjusted HR 0.19 [0.12, 0.30]) and for BNT162b2/Pfizer, mRNA-1273/Moderna, and Ad26.COV2.S/Janssen (adjusted HR=0.25 [0.16, 0.40], 0.14 [0.08, 0.22], and 0.34 [0.17, 0.68] respectively). Among those with anti-spike IgG levels, those with IgG level ≥ 7 had significantly lower risk of a COVID-19 diagnosis (HR=0.25 [0.15, 0.42]) and none experienced a COVID-related hospitalization or death.ConclusionsAmong maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, low anti-spike IgG level is associated with worse COVID-19 related outcomes.Significance StatementSARS-CoV-2 vaccine effectiveness and association between antibody levels and clinical outcomes in maintenance dialysis patients is not known. Between February 1 and October 2, 2021, vaccine effectiveness was 85% against COVID-19 infection and 81% against composite of COVID-related hospitalization or death. COVID-19 case rates and severe outcomes were higher during the Delta dominant period (June 27-October 2, 2021). Increasing time (weeks) since full vaccination status was associated with increased risk for COVID-19 related hospitalization or death. Anti-spike IgG level ≥ 7 had lower risk of a COVID-19 diagnosis and no COVID-related hospitalization or death. Our findings supports utilization of SARS-CoV-2 vaccination and suggests that monitoring SARS-CoV-2 antibody levels and administering additional vaccine doses to maintain adequate immunity will be beneficial.

Rationale & ObjectivesHigh dose influenza vaccine provides better protection against influenza infection in older adults than standard dose vaccine. We compared vaccine seroresponse among hemodialysis patients over 4 months after high dose inactivated (HD-IIV3), standard dose inactivated (SD-IIV4) or recombinant (RIV4) influenza vaccine.Study DesignProspective observational study.Setting & ParticipantsPatients at four hemodialysis clinics who received influenza vaccination. Hemagglutination inhibition titers were measured at baseline and at 1, 2, 3 and 4 months following vaccination with HD-IIV3, SD-IIV4 or RIV4 influenza vaccine.OutcomeThe primary outcome was seroprotection rates at ≥1:40 and ≥1:160 (which correspond to antibody levels providing protection from infection in about 50% and 95% immunocompetent individuals, respectively) at 1, 3 and 4 months after vaccination.Analytical approachWe determined GMT and seroprotection and seroconversion rates. Chi-square or Fisher exact tests were used for categorical data; continuous values were analyzed using Wilcoxon rank-sum tests. Generalized estimating equation was used to determine association between GMT and age.Results254 HD patients received HD-IIV3 (n=141), SD-IIV4 (n=36) or RIV4 (n=77) vaccine. A robust initial seroresponse to influenza A strains was observed after all 3 vaccines, with no difference in seroprotection rates at either the ≥1:40 or ≥1:160 titer at 1 and 2 months. Seroresponses to RIV4 and SD-IIV4 waned thereafter, such that by month 3 and 4, seroprotection by HD-IIV3 was significantly higher. Seroprotection rates were lower to the B strains across all three vaccines. Results trended similarly across patients aged below 65 years.LimitationsDue to use of observational data, bias by unmeasured confounders may exist. Some of the subgroups by age were low in number.ConclusionsHemodialysis patients achieved high seroprotection rates after all 3 vaccines. The seroresponse waned more slowly with HD-IIV3 as compared to SD-IIV4 or RIV4 vaccine.

Background and ObjectivesWhile most maintenance dialysis patients exhibit initial seroresponse to vaccination, concerns remain regarding the durability of this antibody response. This study evaluated immunity over time.Design, setting, participants, and measurementsThis retrospective cohort study included maintenance dialysis patients from a midsize national dialysis provider who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. Immunoglobulin G spike antibodies (SAb-IgG) titers were assessed monthly with routine labs beginning after full vaccination and followed over time; the semiquantitative SAb-IgG titer reported a range between 0 and ≥ 20 U/L. Descriptive analyses compared trends over time by prior history of COVID-19 and type of vaccine received. Time-to-event analyses were conducted for the outcome of loss of seroresponse (SAb-IgG < 1 U/L or development of COVID-19). Cox proportional hazards regression was used to adjust for additional clinical characteristics of interest.ResultsAmong 1898 maintenance dialysis patients, 1567 (84%) had no prior history of COVID-19. Patients without a history of COVID-19 had declining titers over time. Among 441 BNT162b2/Pfizer recipients, median [IQR] SAb-IgG titer declined from 20 [5.99-20] U/L in month 1 to 1.30 [0.15-3.59] U/L by month 6. Among 779 mRNA-1273/Moderna recipients, median [IQR] SAb-IgG titer declined from 20 [20-20] in month 1 to 6.20 [1.74-20] by month 6. The 347 Ad26.COV2.S/Janssen recipients had a lower titer response than mRNA vaccine recipients over all time periods. In time-to-event analyses, Ad26.COV2.S/Janssen and mRNA-1273/Moderna recipients had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first two months after full vaccination was predictive of the durability of the SAb-IgG seroresponse; patients with SAb-IgG titer 1-19.99 U/L were more likely to have loss of seroresponse compared to patients with SAb-IgG titer ≥ 20 U/L (HR 23.9 [95% CI: 16.1-35.5]).ConclusionsVaccine-induced seroresponse wanes over time among maintenance dialysis patients across vaccine types. Early titers after full vaccination predict the durability of seroresponse.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG

ImportanceVaccines against SARS-CoV-2 are highly effective in the general population; however, their efficacy may be diminished in maintenance dialysis patients, a population particularly vulnerable to COVID-19 infection and morbidity.ObjectiveWe assessed vaccine response in a national sample of maintenance dialysis patients and identified predictors of response.DesignRetrospective cohort studySetting130 Dialysis Clinic, Inc (DCI) facilitiesParticipantsMaintenance dialysis patients without known prior COVID-19 or a positive baseline antibody titerExposure(s)Vaccine type and clinical characteristicsMain Outcome(s)Using a semi-quantitative assay for antibodies against SARS-CoV-2 spike antigen, vaccine response was defined as at least one titer ≥1 U/L between 14 and 74 days after completion of a SARS-CoV-2 vaccine series. Regression analysis was used to identify characteristics associated with response.ResultsAmong 1528 patients, 437 received BNT162b2/Pfizer vaccine, 766 received mRNA-1273/Moderna, and 325 received Ad26.COV2.S/Janssen. Serologic response differed significantly by vaccine type: 381/437 (87%) among BNT162b2/Pfizer recipients, 736/766 (96%) among mRNA-1273/Moderna recipients, and 119/325 (37%) among Ad26.COV2.S/Janssen recipients. Vaccine type, older age, immune-modulating medication, history of transplantation, and lower serum albumin were associated with vaccine non-response.Conclusions and RelevanceSerologic response to mRNA vaccines is robust among maintenance dialysis patients. Future research should evaluate durability of this response, correlation between seroresponse and protection from COVID-19, and the role of the AD26.COV2.S/Janssen vaccine in this vulnerable population.

Rationale & Objective Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with COVID-19. We examined the clinical factors that determine kidney recovery in this population. Study Design Multicenter cohort study. Setting & Participants 4221 adults with COVID-19 not receiving kidney replacement therapy who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the “ICU cohort”). Among these, 876 developed AKI-KRT after admission to the ICU (the “AKI-KRT subcohort”). Exposure(s) The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of dialysis initiation. Outcome(s) The outcome for the ICU cohort was estimated glomerular filtration rate (GFR) at hospital discharge. A three-level outcome including death, kidney nonrecovery, and kidney recovery at discharge, was analyzed for the AKI-KRT subcohort. Analytical approach The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. Results Among a total of 4221 patients in the ICU cohort, 2361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower estimated GFR with odds ratios (ORs) of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for CKD GFR categories 3, 4, and 5, respectively, compared to estimated GFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (OR 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and, Critically ill patients with COVID-19 often develop acute kidney injury (AKI). This study of 4221 patients demonstrated that more severe AKI was associated with greater in-hospital mortality and poorer kidney function at hospital discharge. Among the 876 patients who required dialysis for AKI, almost two-thirds died. Among those who survived to discharge, about two-thirds recovered kidney function and were discharged without the need for dialysis. Lower baseline kidney function and reduced urine output were associated with non-recovery of kidney function. Identification of such predictors is important in assessing prognosis among these critically ill patients and has implications for clinical care of individuals critically ill with COVID-19.

Coronavirus disease 2019 (COVID-19) has affected the care and outcomes of patients treated with dialysis worldwide. In this issue of Kidney International, 3 reports highlight the disproportionately severe impact of COVID-19 on patients on dialysis, noting its high prevalence, particularly among patients receiving in-center dialysis. This likely reflects patients' limited ability to physically distance as well as community exposures, including residence in areas with high rates of infection. Patients on dialysis are at extremely high risk should they develop COVID-19, with short-term mortality of 20% or higher. Accordingly, it is imperative that the kidney community intervenes to reduce the threat of COVID-19 in this vulnerable population by focusing on modifiable factors, including universal masking of patients and staff and enhanced screening, including testing for COVID-19 in the patients who are asymptomatic during times of high local prevalence.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory state characterized by phagocytosis of hematopoietic elements. It may be triggered by infection, malignancy, and autoimmune disorders and often progresses to multiorgan failure and even death.A 59-year-old man presented to our hospital for recurrent fevers in the setting of known IgA multiple myeloma complicated by end-stage renal disease requiring dialysis. Infectious workup was negative, and he was diagnosed with HLH. Attempts to treat first with DVR-PACE, then with DVP-PACE resulted in transient improvement, but each time, HLH returned with count recovery. The patient was ultimately treated with pomalidomide and daratumumab, which resulted in HLH resolution without recurrence. Unfortunately, his multiple myeloma continued to progress, and he died several months later.HLH in the setting of multiple myeloma is quite rare; since the establishment of the HLH-2004 diagnostic guidelines, this is only the fourth case published. Furthermore, our patient was treated with the novel therapeutic drug daratumumab, an anti-CD38 monoclonal antibody. Through CD38, daratumumab also works to decrease natural killer (NK) cell activity. Thus, we hypothesize that by reducing the NK cell activity, daratumumab resulted in treatment of his HLH independent of the impact on his multiple myeloma.

Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear.Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability.In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models.A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%).There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Rationale & Objective Underlying kidney disease is an emerging risk factor for more severe COVID-19 illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing kidney disease and investigated the association between degree of underlying kidney disease and in-hospital outcomes. Study Design Retrospective cohort study Settings & Participants 4,264 critically ill COVID-19 patients (143 dialysis patients, 521 chronic kidney disease [CKD] patients, and 3,600 patients without CKD) admitted to ICUs at 68 hospitals in the United States. Predictor(s) Presence (versus absence) of pre-existing kidney disease Outcome(s) In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/ cardiac arrest, thromboembolic event, major bleed, and acute liver injury (secondary) Analytical Approach We used standardized differences to compare patient characteristics (values >0.10 indicate a meaningful difference between groups) and multivariable adjusted Fine and Gray survival models to examine outcome associations. Results Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median [quartile 1-quartile 3] days: 4 [2-9] for dialysis patients; 7 [3-10] for CKD patients; 7 [4-10] for patients without pre-existing kidney disease). More dialysis patients (25%) reported altered mental status than those with CKD (20%, standardized difference = 0.12) and no kidney disease (12%, standardized difference = 0.36). Half of dialysis and CKD patients died within 28-days of ICU admission versus 35% of patients without pre-existing kidney disease. Compared to patients without pre-existing kidney disease, dialysis patients had a higher risk of 28-day in-hospital death (adjusted HR 1.41; 95% CI 1.09, 1.81), while patients with CKD had an intermediate risk (adjusted HR 1.25; 95% CI 1.08, 1.44). Limitations Potential residual confounding Conclusions Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies for this vulnerable population., Individuals with underlying kidney disease may be particularly vulnerable to severe COVID-19 illness, marked by multi-system organ failure, thrombosis, and a heightened inflammatory response. Among 4,264 critically ill adults with COVID-19 admitted to 68 intensive care units across the U.S., we found that both chronic kidney disease and dialysis patients had a ∼50% 28-day in-hospital mortality rate. Patients with underlying kidney disease had higher in-hospital mortality than patients without kidney disease, with patients on maintenance dialysis having the highest risk. As evidenced by differences in symptoms and clinical trajectories, patients with pre-existing kidney disease may have unique susceptibility to COVID-19-related complications which warrants additional study and special consideration in the pursuit and development of targeted therapies.

Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival. Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. Setting: 67 hospitals in the United States. Participants: Adults with COVID-19 admitted to a participating ICU. Measurements: Time to death, censored at hospital discharge, or date of last follow-up. Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Limitation: Observational design. Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. Primary Funding Source: None.

Rationale & objective During the COVID-19 pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 infection in this population. Study design Retrospective cohort study. Setting & participants Maintenance dialysis patients in clinics with at least one patient with a positive test for SARS-CoV-2 from February to June 2020, treated by a mid-size national dialysis provider. Predictors Demographics, dialysis characteristics, residence in a congregate setting, comorbid conditions, measures of frailty, and use of selected medications. Outcomes COVID-19 defined as having a positive SARS-CoV-2 test and all-cause mortality among those with COVID-19. Analytical approach Logistic regression analyses to identify clinical characteristics associated with COVID-19and risk factors associated with mortality among patients following COVID-19. Results 438/7948 (5.5%) maintenance dialysis patients developed COVID-19. Male sex, Black race, in-center dialysis (vs. home dialysis), treatment at an urban clinic, residence in a congregate setting, and greater comorbidity were associated with contracting COVID-19. Odds of COVID-19 was 17-fold higher for those residing in a congregate setting [OR = 17.10 (95% CI 13.51, 21.54)]. Of the 438 maintenance dialysis patients with COVID-19, 109 (24.9%) died. Older age, heart disease, and markers of frailty were associated with mortality. Limitations No distinction between symptomatic and asymptomatic SARS-CoV-2 positivity, with asymptomatic screening limited by testing capacity during this initial COVID-19 surge period. Conclusions COVID-19 is common among patients receiving maintenance dialysis, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.

Patterning multiple cell types is a critical step for engineering functional tissues, but few methods provide three-dimensional positioning at the cellular length scale. Here, we present a “bottom-up” approach for fabricating multicellular tissue constructs that utilizes DNA-templated assembly of 3D cell-laden hydrogel microtissues. A flow focusing-generated emulsion of photopolymerizable prepolymer is used to produce 100 μm monodisperse microtissues at a rate of 100 Hz (10[superscript 5] h[superscript −1]). Multiple cell types, including suspension and adherently cultured cells, can be encapsulated into the microtissues with high viability ([similar]97%). We then use a DNA coding scheme to self-assemble microtissues “bottom-up” from a template that is defined using “top-down” techniques. The microtissues are derivatized with single-stranded DNA using a biotin–streptavidin linkage to the polymer network, and are assembled by sequence-specific hybridization onto spotted DNA microarrays. Using orthogonal DNA codes, we achieve multiplexed patterning of multiple microtissue types with high binding efficiency and >90% patterning specificity. Finally, we demonstrate the ability to organize multicomponent constructs composed of epithelial and mesenchymal microtissues while preserving each cell type in a 3D microenvironment. The combination of high throughput microtissue generation with scalable surface-templated assembly offers the potential to dissect mechanisms of cell–cell interaction in three dimensions in healthy and diseased states, as well as provides a framework for templated assembly of larger structures for implantation.