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Background: Antibody (AB) response to Ad26.COV2.S vaccine (AdV) was observed to be lower than with mRNA vaccines in dialysis patients and additional vaccine doses were recommended. We conducted a quality improvement project in Fresenius Kidney Care clinics to track AB response in dialysis patients initially administered AdV who later received or did not receive additional vaccine doses. Method(s): AB response was measured in remnant blood with semiquantitative chemiluminescent assay detecting IgG AB directed against receptor binding domain of S1 subunit of SARS-CoV-2 spike antigen (Siemens);AB index >1 was considered reactive, >7 as adequate, and > 750 was maximum detected. All patients who received an AdV, had 2 AB measures after vaccination, and were not Covid-19 positive/suspected cases were included in the analysis. Patients were classified into 4 groups based on vaccine doses received: AdV single dose (n=103);AdV+AdV (n=8);AdV+mRNA (n=329);AdV+mRNA+mRNA (n=14). First AB measurement occurred after initial AdV dose and Last AB measurements occurred after additional vaccine doses. Result(s): AB was measured, on average, 97 (sd 12) days and 325 (sd 14) days after first AdV dose for First AB and Last AB measurements, respectively. Distribution of AB responses are shown in Figure. At Last AB measurement, AB index <= 7 was common for AdV and AdV + AdV groups (43% and 51%, respectively). However, it was rare in AdV+mRNA and AdV+mRNA+mRNA groups (7% and 0%, respectively). Conclusion(s): Patients who were initially vaccinated with AdV, had improved AB response after one or two mRNA vaccine doses. This response was more pronounced than when patients were administered an additional AdV dose.
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Background: To help protect dialysis patients from COVID-19, efforts have been made to ensure widespread vaccination, however, reports have shown waning antibody (AB) levels that may decline faster than the general population. The current analysis examines AB response to a 3rd or booster dose of mRNA-1273 vaccine among dialysis patients across 7 dialysis clinics in Massachusetts. Method(s): All patients received 2 mRNA-173 doses and had AB measured 250+ days after 2nd dose (when additional/booster doses were available). Covid-19 positive/suspected cases were not included in the analysis. As part of a quality improvement project, patients were classified into 3 groups based on further doses received: mRNA booster (Booster 50 mcg), mRNA additional dose (Additional;100 mcg), and no second dose or booster (Primary). AB response was measured in remnant blood with semiquantitative chemiluminescent assay detecting IgG AB directed against receptor binding domain of S1 subunit of SARS-CoV-2 spike antigen (Siemens);AB index >1 was considered reactive, >7 as adequate, and > 750 was maximum detected. For time periods with multiple AB measurements, the latest AB value was utilized. Result(s): Distribution of AB levels before and after booster/additional dose are presented in figure. Before booster/additional dose few patients had AB levels > 750 (2%). After booster or additional dose, 58% and 50% had AB levels > 750, respectively. AB response <= 7 was common (46%) before and rare after booster and additional dose (2% and 0%). Conclusion(s): After the administration of booster/additional doses of mRNA COVID-19 vaccines, nearly all patients had at least adequate AB response and the majority had maximum response. This is contrasted with the patients not receiving booster/additional dose, where 72% had adequate AB response and 27% had maximum response.
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Background: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that promotes erythropoiesis and improves iron availability in patients with anemia of chronic kidney disease (CKD). This trial aims to provide practical data on roxadustat use in dialysis patients with anemia via a semi-pragmatic evaluation of introduction into providers' practices (Fresenius Medical Care). Methods: This open-label, single-arm study assesses the efficacy and safety of roxadustat in correcting/maintaining hemoglobin (Hb) in patients with CKD-related anemia receiving in-center/home dialysis at nine US sites (NCT04410198). Initial roxadustat dose is weight-based (erythropoiesis-stimulating agent [ESA]-naïve patients) or guided by an ESA dose-conversion algorithm (ESA patients), in this trial targeting Hb=11±1 g/dL. Roxadustat dose is titrated every 4 weeks based on Hb level or rate of change, with 24-week treatment duration and up to 1-year extension. Efficacy is assessed by change from baseline in Hb and proportion of patients achieving mean Hb ≥10 g/dL averaged over weeks 16-24. Exploratory endpoints include time to first red blood cell transfusion, proportion of patients achieving mean Hb ≥10 g/dL in first 8 weeks, intravenous iron use, and dosing adherence. Safety endpoints include treatment-emergent adverse events (AE), with COVID-19 positivity an AE of special interest. Results: This ongoing trial was successfully initiated and enrolled (n=203) during the COVID-19 pandemic, with modifications for home dialysis. Baseline characteristics appear representative of the US dialysis population (Table). Conclusions: This trial adds to phase 3 studies of roxadustat by evaluating its use in treating anemia of CKD in home/in-center dialysis patients during the COVID-19 pandemic, while providing a view into operationalization and ease of real-world use. Full study results will be presented. (Table Presented) .
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Background: Vaccine unresponsiveness and rapid AB level decline after successful vaccination have been barriers to antiviral strategies in ESKD populations. We report an interim analysis of a quality improvement project characterizing the temporal AB response to COVID-19 vaccination across 7 dialysis clinics in MA. Methods: Chronic dialysis pts received 2 doses of mRNA vaccine at prescribed intervals. AB response was measured in remnant blood with semiquantitative chemiluminescent assay detecting IgG AB directed against receptor binding domain of S1 subunit of SARS-CoV-2 spike antigen (Siemens);AB index ≥1 was considered reactive. AB index >7 produce plaque reduction neutralization test (PRNT50) titers >1:80 dilution recommended by FDA standard for measuring neutralizing titer. Results: 211 pts received the 2-dose mRNA vaccine (mRNA-1273, 1 given BNT162b2). On average (ave) AB peaked at day 19 post 2nd vaccine;peak index was >7 for 97% of pts. Pts with AB peak >7 had higher serum albumin vs pts with AB peak ≤ 7 (3.8 vs 3.4 g/dl). Among pts with AB measured after peak AB index (n=188), ave AB index decreased by 125 (46% reduction) over an ave 46 days. Ave decreases from peak were 51% in pts with no prior COVID-19 history (n=162) and 20% in pts with COVID-19 history (n=26);illustrated in subset with ≥5 AB measurements ≥ 45 days post 2nd vaccine dose (n=114, Figure). No symptomatic COVID-19 cases were reported. Conclusions: mRNA-1273 is a highly reactive vaccine producing reactive AB in all, and >7 index in 97% of vaccinated ESKD pts. However, if AB index confers immunity, blunted and rapid decline of circulating AB may place ESKD pts at risk of future COVID-19 infection. Monitoring post-vaccination AB levels may be important for ESKD pts (especially hypoalbuminemic pts) and may guide future vaccination requirements.
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Background: The COVID-19 viral vector (VV) vaccine's single dose and routine storage requirements may be preferred to the mRNA-based vaccine's 2 doses and low temperature storage requirements. We report an interim analysis of a quality improvement project performed at 2 Arizona dialysis clinics comparing the AB response to VV vaccine with mRNA vaccine in ESKD pts. Methods: Pts received either the VV vaccine (Ad26.COV2.S) administered in the dialysis clinic or mRNA vaccines (BNT162b2, mRNA-1273) administered in the community. AB response was assessed with remnant blood and a semi-quantitative chemiluminescent assay for IgG directed against the receptor binding domain of the SARS-CoV-2 spike antigen. Values >7.0 Index produce plaque reduction neutralization test (PRNT50) titers greater than 1:80 dilution recommended by the FDA standard for measuring neutralizing titer. Results: AB response was evaluated at an average of 22 days post vaccination (≥14 days post Ad26.COV2.S or post 2nd mRNA vaccine). 36/45 pts (80%) who received the VV vaccine failed to develop an AB index >7 after ≥14 days post vaccine compared to 5/31 pts (16%) who received an mRNA vaccine (84% achieved AB index >7);all 5 pts had no prior COVID-19 history. Of pts receiving the VV vaccine with prior history of COVID-19, 22% of pts had AB index <8 after 14 days post vaccine. 41 pts receiving the VV vaccine had additional AB measurements in the next 14-37 days (ave 26 days after prior measure). In 34 pts with no prior history of COVID-19, 3 pts achieved AB index >7 in the recent sample and had previously been < 1 (n=1) or 1-7 (n=2), bringing the total number with AB > 7 from 2 to 5 (15%). AB levels remained unchanged in pts with a prior history of COVID-19 (n=9). No demographic or laboratory differences were observed. Conclusions: Our data support the contention that the available VV-based vaccine against the SARS-CoV-2 virus is not effective in producing AB response in most ESKD pts especially when compared to an mRNA counterpart. If AB indices predict immunity and other studies support our findings, alternative vaccination strategies in ESKD pts vaccinated with VV vaccines is needed.
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Background: Monitoring real-time acceleration, plateaus, and deceleration of infection rates is important for healthcare planning during a pandemic. We implemented methodology to continuously monitor daily cases and changes of COVID-19 case rates among individuals with ESKD receiving care in a large dialysis organization. Methods: We identified patients with ESKD receiving dialysis in a Fresenius Medical Care North America (FMCNA) dialysis facility who tested positive for COVID-19. We fit a loess curve to the daily cumulative number of identified cases and computed the first and second derivative of the fitted curve to assess rate of change and change in rate of change, respectively, over time. We used these visualization techniques to monitor trends in case rates at the national and state levels. Results: By May 15, 2020, there were 5,513 confirmed COVID-19 cases among patients receiving dialysis in an FMCNA facility. Mean age was 63.6 years, 57% were male, and 71% of confirmed cases had diabetes. Nationally, during the peak infection period in early April, new cases routinely exceeded 150 per day and there was a steady acceleration in growth of cases until the second week of April. As of May 15, 2020, among states with sufficient data, 2 states demonstrated continued acceleration, 10 demonstrated deceleration, and 13 plateaued in rate of growth. Conclusions: The timing of the acceleration in growth of COVID-19 cases among individuals with ESKD followed national trends in the general population. Varying patterns of plateauing and deceleration of cases at the state level were observed in the ESKD population. Real-time monitoring of disease rates in high-risk populations, such as individuals with ESKD, is needed to plan for continuously changing healthcare demands during a pandemic.
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Background: COVID-19 has been associated with the development of AKI, and the incidence of AKI-D may be as high as 3-5% in patients hospitalized with COVID-19. We examined the initiation of outpatient (OP) dialysis for AKI-D following a diagnosis of COVID-19. Methods: We identified patients who were diagnosed with COVID-19 prior to initiating OP dialysis for AKI-D in a Fresenius Medical Care North America (FMCNA) dialysis facility between March 30, 2020 and May 22, 2020. COVID-19 diagnosis was based on information provided at the time of referral or data collected within FMCNA. We assessed demographics, geographic location, and select initial outpatient lab values. We followed patients from initiation of OP dialysis until the earliest of recovery of kidney function, transition to ESKD, death, loss to follow-up (typically, transfer to another dialysis provider), or May 24, 2020, and estimated the cumulative incidence of these outcomes. Results: The cohort comprised 127 patients who were diagnosed with COVID-19 prior to initiating OP dialysis for AKI-D. Mean age was 56.3 ± 14.7 years and 64% were male. Initiation of OP dialysis for AKI-D was observed in regions with a known high incidence of COVID-19 disease (Figure). The median hemoglobin, platelet count and albumin at dialysis initiation were 8.9 g/dL, 271,000 per microliter, and 3.2 g/dL, respectively. During a median follow-up period of 19 days, 18 (14.2%) patients recovered kidney function, 2 (1.6%) transitioned to ESKD, and 2 (1.6%) died. Conclusions: In an approximate 7-week period, 127 adults started OP dialysis for AKI-D following a diagnosis of COVID-19. Unfortunately, information regarding the clinical course of COVID-19 preceding OP initiation of dialysis was not available and using information at the time of referral may have resulted in misclassification of COVID-19 disease. Nevertheless, these are important findings and warrant further study, especially with respect to long-term outcomes in this population.
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Background: The frequency of evaluations in hemodialysis (HD) care affords opportunities to assess profiles that may characterize onset of the 2019 coronavirus disease (COVID-19). We aimed to characterize the trajectories of clinical/laboratory assessments before COVID-19 diagnosis in HD patients. Methods: We assessed data from HD patients with known COVID-19 dialyzed at Fresenius Kidney Care in the United States between 02 Mar and 09 Apr 2020. We computed mean daily values for 40 variables 90 days before a positive rRT-PCR test (COVID-19+). Nonparametric smoothing splines were used to fit data of individual trajectories and estimate the mean change over time. Results: There were 1294 HD patients with COVID-19 (mean age 64±14 years, 60% male, 47% white race, 69% had diabetes, and 24% had coronary artery disease). Mean pre- HD body temperature (primarily oral) increased by about 1° Fahrenheit (F) over 10 days before COVID-19+ test and approached 99° F at diagnosis (Fig 1A). Mean interdialytic weight gain decreased by about 0.75 kg (Fig 1B) over 14 days before COVID-19+ test;concurrent decreases of about 20 minutes were seen in HD treatment time. Mean neutrophil-to-lymphocyte ratio had mild increases (Fig 1C), while mean platelet counts decreased by about 40×109/L over 14 days before COVID-19+ test (Fig 1D). Trajectories of many variables (vitals, heparin, hematology, nutrition, bone, anemia) were observed to change before COVID-19+ test, yet alternations were generally minor. Conclusions: The trajectories of several clinical/laboratory parameters appeared to change before COVID-19 diagnosis in HD patients. Many changes were small and may not be independently useful in identifying onset of COVID-19. Mean pre-HD body temperature before SARS-CoV-2 infection was 97.4° F and should be considered in screening. Findings may have utility in prediction model development. Further comparisons to patients without COVID-19 are needed.
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Background: Hemodialysis (HD) patients are vulnerable to the 2019 coronavirus disease (COVID-19) due to older age and common coexistence of comorbidities. Fever and respiratory illness (RI) are common symptoms of COVID-19. In order to create a disease surveillance tool and anticipate areas of COVID-19 outbreak, we aimed to assess the trends in fever and RI symptoms in HD patients treated at a national dialysis provider network in the United States during the pandemic. Methods: We used data from HD patients actively treated between Jan 1 2018 ad May 16 2020 at a national dialysis provider network of large integrated health care company. If the body temperature of the patient either before or after the treatment was greater than 100 degrees Fahrenheit, then the patient was identified as exhibiting the symptom of fever. If the patient complained of shortness of breath, wheezing, runny nose, bloody cough, dry cough or purulent cough, then in this analysis the patient was identified as exhibiting the symptom of RI. Results: The total patients count ranged from 196,774 to 209,475 per week while the total count of HD treatments ranged from 413,477 to 454,215. For the year 2020, a clear increase in trend for number of patients was observed after week 11 (03/08-03/14/2020) for RI symptoms (Figure 1A) and week 12 (3/15-3/21/2020) for fever symptom (Figure 1B). Both increasing trends spike at the week 15 (04/05-04/11/2020) and decline thereafter. Conclusions: HD patients appear to exhibit a different trend in RI and fever symptoms during the year 2020 compared to concurrent periods in 2018 and 2019. which coincides with COVID-19 outbreak. Routine surveillance of dialysis patients may allow for early identification of COVID-19 outbreaks.