Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases in a large US healthcare system had at least 55% (95% confidence interval: 43-69%) higher adjusted odds of prior documented infection than time-matched BA.2 cases, as well as 15% (9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses.

Purpose

The early period after chronic kidney disease (CKD) patients transition to end-stage renal disease (ESRD) represents the highest mortality risk but is variable among different patient populations and clinical circumstances. We compared early mortality outcomes among a diverse CKD population that transitioned to ESRD.

Methods

A retrospective cohort study (1/1/2002 through 12/31/2013) of CKD patients (age ≥ 18 years) who transitioned to peritoneal dialysis (PD), hemodialysis (HD) with arteriovenous fistula/grafts, and HD with catheters was performed. Multivariable Cox regression modeling was used to estimate 6-month all-cause mortality hazard ratios (HR) among the three treatment groups after adjustment for patient and clinical characteristics.

Results

Among 5373 ESRD patients (62.7 years, 41.3% females, 37.5% Hispanics, 13.3% PD, 34.9% HD with fistula/graft, 51.8% HD with catheter), 551 (10.3%) died at 6 months. Mortality rates were highest immediately after transition (299 deaths per 1000 person-years in first month). Compared to PD patients, the 6-month mortality HR (95% CI) was 1.87 (1.06-3.30) in HD with fistula/graft patients and 3.77 (2.17-6.57) in HD with catheter patients. Inpatient transition (HR 1.32), acute kidney injury (HR 2.06), and an eGFR ≥ 15 vs 5-9 (HR 1.68) at transition were also associated with higher early mortality risk.

Conclusion

Among a diverse CKD population who transitioned to ESRD, we observed considerable differences in early mortality risk among PD, HD with fistula/graft, and HD with catheter patients. The identification of patient-specific and clinical environmental factors related to high early mortality may provide insights for managing advanced stages of CKD and shared decision making.

In the original publication, age stratified mortality rates were incorrectly added in Fig. 2. The correct Fig. 2 is given below.

Rational & objective

Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether β-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis.

Study design

Retrospective cohort study.

Setting & participants

Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included.

Exposures

Patients were considered treated with β-blockers if they had a quantity of drug dispensed covering the dialysis transition date.

Outcomes

All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis.

Analytical approach

Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between β-blocker use and study outcomes.

Results

3,503 patients were included in the study. There were 2,115 (60.4%) patients using β-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any β-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization.

Limitations

The observational nature of our study could not fully account for residual confounding.

Conclusions

Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Introduction

Lower early mortality observed in peritoneal dialysis (PD) compared with hemodialysis (HD) may be due to differential pre-end-stage renal disease (ESRD) care and the stable setting of transition to dialysis where PD starts are more frequently outpatient rather than during an unscheduled hospitalization. To account for these circumstances, we compared early mortality among a matched cohort of PD and HD patients who had optimal and outpatient starts.

Methods

Retrospective cohort study performed among patients with chronic kidney disease (CKD) who transitioned to ESRD from 1 January 2002 to 31 March 2015 with an optimal start in an outpatient setting. Optimal start defined as (i) HD with an arteriovenous graft or fistula or (ii) PD. Propensity score modeling factoring age, race, sex, comorbidities, estimated glomerular filtration rate (eGFR) level, and change in eGFR before ESRD was used to create a matched cohort of HD and PD. All-cause mortality was compared at 6 months, 1 year, and 2 years posttransition to ESRD.

Results

Among 2094 patients (1398 HD and 696 PD) who had optimal outpatient transition to ESRD, 541 HD patients were propensity score-matched to 541 PD patients (caliper distance <0.001). All-cause mortality odds ratios (OR) in PD compared with HD were 0.79 (0.39-1.63), 0.73 (0.43-1.23), and 0.88 (0.62-1.26) for 6 months, 1 year, and 2 years, respectively. Time-varying analysis accounting for modality switch (19% PD, 1.9% HD) demonstrated a mortality hazard ratio of 0.94 (0.70-1.24).

Conclusion

Among an optimal start CKD cohort that transitioned to ESRD on an outpatient basis, we found no evidence of differences in early mortality between PD and HD.

Background

In the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA.

Methods

In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2.

Findings

7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6-77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9-93·8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89·6% (50·2-97·8).

Interpretation

In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test.

Funding

US Centers for Disease Control and Prevention and US National Institutes of Health.