A retrospective cohort study predicting and validating impact of the COVID-19 pandemic in individuals with chronic kidney disease.

Chronic kidney disease (CKD) is associated with increased risk of baseline mortality and severe COVID-19, but analyses across CKD stages, and comorbidities are lacking. In prevalent and incident CKD, we investigated comorbidities, baseline risk, COVID-19 incidence, and predicted versus observed one-year excess death. In a national dataset (NHS Digital Trusted Research Environment [NHSD TRE]) for England encompassing 56 million individuals), we conducted a retrospective cohort study (March 2020 to March 2021) for prevalence of comorbidities by incident and prevalent CKD, SARS-CoV-2 infection and mortality. Baseline mortality risk, incidence and outcome of infection by comorbidities, controlling for age, sex and vaccination were assessed. Observed versus predicted one-year mortality at varying population infection rates and pandemic-related relative risks using our published model in pre-pandemic CKD cohorts (NHSD TRE and Clinical Practice Research Datalink [CPRD]) were compared. Among individuals with CKD (prevalent:1,934,585, incident:144,969), comorbidities were common (73.5% and 71.2% with one or more condition[s] in respective data sets, and 13.2% and 11.2% with three or more conditions, in prevalent and incident CKD), and associated with SARS-CoV-2 infection, particularly dialysis/transplantation (odds ratio 2.08, 95% confidence interval 2.04-2.13) and heart failure (1.73, 1.71-1.76), but not cancer (1.01, 1.01-1.04). One-year all-cause mortality varied by age, sex, multi-morbidity and CKD stage. Compared with 34,265 observed excess deaths, in the NHSD-TRE and CPRD databases respectively, we predicted 28,746 and 24,546 deaths (infection rates 10% and relative risks 3.0), and 23,754 and 20,283 deaths (observed infection rates 6.7% and relative risks 3.7). Thus, in this largest, national-level study, individuals with CKD have a high burden of comorbidities and multi-morbidity, and high risk of pre-pandemic and pandemic mortality. Hence, treatment of comorbidities, non-pharmaceutical measures, and vaccination are priorities for people with CKD and management of long-term conditions is important during and beyond the pandemic.

Outcome and effect of vaccination in SARS-CoV-2 Omicron infection in hemodialysis patients: a cohort study.

BACKGROUND: Hemodialysis patients are at high risk of Covid-19, though vaccination has significant efficacy in preventing and reducing the severity of infection. Little information is available on disease severity and vaccine efficacy since the dissemination of the Omicron variant. METHODS: In a multi-center study, during a period of the epidemic driven by the Omicron variant, all hemodialysis patients positive for SARS-CoV-2 were identified. Outcomes were analyzed according to predictor variables including vaccination status. Risk of infection was analyzed using a Cox proportional hazards model. RESULTS: SARS-CoV-2 infection was identified in 1126 patients including 200 (18%) unvaccinated, 56 (5%) post first dose, 433 (38%) post second dose, and 437 (39%) at least 7 days beyond their third dose. The majority of patients had a mild course but 160 (14%) were hospitalized and 28 (2%) died. In regression models adjusted for age and comorbidity, two-dose vaccination was associated with a 39% (95%CI: 2%-62%) reduction in admissions, but third doses provided additional protection, with a 51% (95%CI: 25%-69%) further reduction in admissions. Among 1265 patients at risk at the start of the observation period, SARS-CoV-2 infection was observed in 211 (17%). Two-dose vaccination was associated with a 41% (95%CI: 3%-64%) reduction in the incidence of infection, with no clear additional effect provided by third doses. CONCLUSIONS: These data demonstrate lower incidence of SARS-CoV-2 infection after vaccination in dialysis patients during an Omicron dominant period of the epidemic. Among those developing infection, severe illness was less common with prior vaccination, particularly after third vaccine doses.

Automated Library Construction and Analysis for High-Throughput Nanopore Sequencing of SARS-CoV-2.

BACKGROUND: To support the implementation of high-throughput pipelines suitable for SARS-CoV-2 sequencing and analysis in a clinical laboratory, we developed an automated sample preparation and analysis workflow. METHODS: We used the established ARTIC protocol with approximately 400 bp amplicons sequenced on Oxford Nanopore's MinION. Sequences were analyzed using Nextclade, assigning both a clade and quality score to each sample. RESULTS: A total of 2179 samples on twenty-five 96-well plates were sequenced. Plates of purified RNA were processed within 12 h, sequencing required up to 24 h, and analysis of each pooled plate required 1 h. The use of samples with known threshold cycle (Ct) values enabled normalization, acted as a quality control check, and revealed a strong correlation between sample Ct values and successful analysis, with 85% of samples with Ct < 30 achieving a "good" Nextclade score. Less abundant samples responded to enrichment with the fraction of Ct > 30 samples achieving a "good" classification rising by 60% after addition of a post-ARTIC PCR normalization. Serial dilutions of 3 variant of concern samples, diluted from approximately Ct = 16 to approximately Ct = 50, demonstrated successful sequencing to Ct = 37. The sample set contained a median of 24 mutations per sample and a total of 1281 unique mutations with reduced sequence read coverage noted in some regions of some samples. A total of 10 separate strains were observed in the sample set, including 3 variants of concern prevalent in British Columbia in the spring of 2021. CONCLUSIONS: We demonstrated a robust automated sequencing pipeline that takes advantage of input Ct values to improve reliability.

Severity of COVID-19 after Vaccination among Hemodialysis Patients: An Observational Cohort Study.

BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis are at high risk from coronavirus disease 2019 (COVID-19) and demonstrate impaired immune responses to vaccines. There have been several descriptions of their immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but few studies have described the clinical efficacy of vaccination in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a multicenter observational study of the London hemodialysis population undergoing surveillance PCR testing during the period of vaccine rollout with BNT162b2 and AZD1222, all of those positive for SARS-CoV-2 were identified. Clinical outcomes were analyzed according to predictor variables, including vaccination status, using a mixed effects logistic regression model. Risk of infection was analyzed in a subgroup of the base population using a Cox proportional hazards model with vaccination status as a time-varying covariate. RESULTS: SARS-CoV-2 infection was identified in 1323 patients of different ethnicities (Asian/other, 30%; Black, 38%; and White, 32%), including 1047 (79%) unvaccinated, 86 (7%) after first-dose vaccination, and 190 (14%) after second-dose vaccination. The majority of patients had a mild course; however, 515 (39%) were hospitalized, and 172 (13%) died. Older age, diabetes, and immune suppression were associated with greater illness severity. In regression models adjusted for age, comorbidity, and time period, prior two-dose vaccination was associated with a 75% (95% confidence interval, 56 to 86) lower risk of admission and 88% (95% confidence interval, 70 to 95) fewer deaths compared with unvaccinated patients. No loss of protection was seen in patients over 65 years or with increasing time since vaccination, and no difference was seen between vaccine types. CONCLUSIONS: These data demonstrate a substantially lower risk of severe COVID-19 after vaccination in patients on dialysis who become infected with SARS-CoV-2.

Risk of COVID-19 Disease, Dialysis Unit Attributes, and Infection Control Strategy among London In-Center Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Patients receiving in-center hemodialysis treatment face unique challenges during the coronavirus disease 2019 (COVID-19) pandemic, specifically the need to attend for treatment that prevents self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We explored the role of variables, including community disease burden, dialysis unit attributes (size and layout), and infection control strategies, on rates of COVID-19 among patients receiving in-center hemodialysis in London, United Kingdom, between March 2, 2020 and May 31, 2020. The two outcomes were defined as (1) a positive test for infection or admission with suspected COVID-19 and (2) admission to the hospital with suspected infection. Associations were examined using a discrete time multilevel time-to-event analysis. RESULTS: Data on 5755 patients dialyzing in 51 units were analyzed; 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between March 2 and May 31, 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates, and dialysis unit size. A greater number of available side rooms and the introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices, nor with any of the different isolation strategies. CONCLUSIONS: Rates of COVID-19 in the in-center hemodialysis population relate to individual factors, underlying community transmission, unit size, and layout.

Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study.

BACKGROUND: Severe COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19. METHODS: In this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients. FINDINGS: The median age at death of our cohort of ten patients was 73 years (IQR 52-79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients. INTERPRETATION: Our series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19. FUNDING: Imperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.

Epidemiology of COVID-19 in an Urban Dialysis Center.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, many countries have instituted population-wide measures for social distancing. The requirement of patients on dialysis for regular treatment in settings typically not conducive to social distancing may increase their vulnerability to COVID-19. METHODS: Over a 6-week period, we recorded new COVID-19 infections and outcomes for all adult patients receiving dialysis in a large dialysis center. Rapidly introduced control measures included a two-stage routine screening process at dialysis entry (temperature and symptom check, with possible cases segregated within the unit and tested for SARS-CoV-2), isolated dialysis in a separate unit for patients with infection, and universal precautions that included masks for dialysis nursing staff. RESULTS: Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. We observed clustering in specific units and on specific shifts, with possible implications for aspects of service design, and high rates of nursing staff illness. A predictive epidemic model estimated a reproduction number of 2.2; cumulative cases deviated favorably from the model from the fourth week, suggesting that the implemented measures controlled transmission. CONCLUSIONS: The COVID-19 epidemic affected a large proportion of patients at this dialysis center, creating service pressures exacerbated by nursing staff illness. Details of the control strategy and characteristics of this epidemic may be useful for dialysis providers and other institutions providing patient care.