SARS-CoV-2 neutralizing antibody response after three doses of mRNA1273 vaccine and COVID-19 in hemodialysis patients.

Background: In hemodialysis patients, a third vaccination is frequently administered to augment protection against coronavirus disease 2019 (COVID-19). However, the newly emerged B.1.1.159 (Omicron) variant may evade vaccinal protection more easily than previous strains. It is of clinical interest to better understand the neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants after booster vaccine or COVID-19 infection in these mostly immunocompromised patients. Methods: Hemodialysis patients from four dialysis centers were recruited between June 2021 and February 2022. Each patient provided a median of six serum samples. SARS-CoV-2 neutralizing antibodies (nAbs) against wild type (WT) or Omicron were measured using the GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit. Results: Forty-two patients had three doses of mRNA1273. Compared to levels prior to the third dose, nAb-WT increased 18-fold (peak at day 23) and nAb-Omicron increased 23-fold (peak at day 24) after the third dose. Peak nAb-WT exceeded peak nAb-Omicron 27-fold. Twenty-one patients had COVID-19 between December 24, 2021, and February 2, 2022. Following COVID-19, nAb-WT and nAb-Omicron increased 12- and 40-fold, respectively. While levels of vaccinal and post-COVID nAb-WT were comparable, post-COVID nAb-Omicron levels were 3.2 higher than the respective peak vaccinal nAb-Omicron. Four immunocompromised patients having reasons other than end-stage kidney disease have very low to no nAb after the third dose or COVID-19. Conclusions: Our results suggest that most hemodialysis patients have a strong humoral response to the third dose of vaccination and an even stronger post-COVID-19 humoral response. Nevertheless, nAb levels clearly decay over time. These findings may inform ongoing discussions regarding a fourth vaccination in hemodialysis patients.

SARS-COV-2 Neutralizing Antibody Response to Booster Vaccination in Patients on Hemodialysis

BACKGROUND AND AIMS SARS-CoV-2 antibody titers after two doses of vaccination decrease over time. Hemodialysis patients are especially vulnerable to COVID-19 as they are immunocompromised, putting them at higher risk of infection and poorer response to vaccines. Therefore, administrating the third dose (‘booster’) in these patients is key to reduce COVID-19 infections and prevent severe illness. Dialysis patients were among the first group of patients who received booster vaccinations. To study the humoral response to the third injection in this group, we collected serum from 33 patients on hemodialysis and measured neutralizing antibody titers against SARS-CoV-2 before and after their booster doses. METHOD Patients were recruited from a dialysis center in New York City, NY from June to September 2021. Data on COVID-19 vaccination and demographics were collected upon enrollment. Blood samples were taken after enrollment. SARS-CoV-2 neutralization antibodies were assayed using the GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit (Cat#L00847-A). Corresponding neutralizing antibody titers are presented as Unit/mL (U/mL). RESULTS A total of 33 in-center hemodialysis patients who had received three doses of vaccination were studied. Patients had a mean age of 61 years, 23 (70%) were male. Out of these, 31 (94%) patients received three doses of mRNA-1273 (Moderna), and two patients received the BNT162b2 (Pfizer BioNTech) vaccine. A total of 138 serum samples were analyzed (ranging from 156 days before to 85 days after the booster). Figure 1 shows the antibody titer distribution of all samples in these 33 patients. Each color indicates an individual patient. Each patient has up to 12 data points before and after the booster. The mean neutralizing antibody titers of all 48 data points pre-booster is 29.291 U/mL (range: 228–188.600). Seven days post-booster, the mean neutralizing antibody titer is 73.088 U/mL (range: 12.401–254.504). Mean titer is 169.826 U/mL (range: 17.830–375.046) at 14–28 days post-booster. After the peak time, we observe a decline of the titers. At 72–85 days, the mean titer is 72.179 (range: 33.702–204.382). We fitted a nonparametric mixed effects model with an adaptive spline and a random intercept for each subject to neutralizing antibody titers on the log10 scale. The estimate of the mean trajectory and its 95% confidence interval are shown in Fig. 2. The estimated peak time is 18.2 days with a 95% confidence interval (0–27.7). CONCLUSION Our results suggest that hemodialysis patients have a strong humoral response to booster vaccination. Neutralizing antibody titers peak at 18 days post-booster and wane to an average of 42% of peak value after 10–12 weeks.FIGURE 1: Time-course of neutralizing antibody titers before and after booster vaccination. The colors identify individual hemodialysis patients.FIGURE 2: A nonparametric mixed effects model with an adaptive spline and a random intercept for each subject to neutralizing antibody titers. The red line indicates the average titer, and the gray area indicates the 95% confidence interval. The circles are means across all data points.

SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-19.

Background: To date, it is unclear whether SARS-CoV-2 is present in spent dialysate from patients with COVID-19 on peritoneal dialysis (PD). Our aim was to assess the presence or absence of SARS-CoV-2 in spent dialysate from patients on chronic PD who had a confirmed diagnosis of COVID-19. Methods: Spent PD dialysate samples from patients on PD who were positive for COVID-19 were collected between March and August 2020. The multiplexed, real-time RT-PCR assay contained primer/probe sets specific to different SARS-CoV-2 genomic regions and to bacteriophage MS2 as an internal process control for nucleic acid extraction. Demographic and clinical data were obtained from patients' electronic health records. Results: A total of 26 spent PD dialysate samples were collected from 11 patients from ten dialysis centers. Spent PD dialysate samples were collected, on average, 25±13 days (median, 20; range, 10-45) after the onset of symptoms. The temporal distance of PD effluent collection relative to the closest positive nasal-swab RT-PCR result was 15±11 days (median, 14; range, 1-41). All 26 PD effluent samples tested negative at three SARS-CoV-2 genomic regions. Conclusions: Our findings indicate the absence of SARS-CoV-2 in spent PD dialysate collected at ≥10 days after the onset of COVID-19 symptoms. We cannot rule out the presence of SARS-CoV-2 in spent PD dialysate in the early stage of COVID-19.

Effect of Statewide Lockdown in Response to COVID-19 Pandemic on Physical Activity Levels of Hemodialysis Patients.

BACKGROUND/OBJECTIVES: On March 22, 2020, a statewide stay-at-home order for nonessential tasks was implemented in New York State. We aimed to determine the impact of the lockdown on physical activity levels (PAL) in hemodialysis patients. METHODS: Starting in May 2018, we are conducting an observational study with a 1-year follow-up on PAL in patients from 4 hemodialysis clinics in New York City. Patients active in the study as of March 22, 2020, were included. PAL was defined by steps taken per day measured by a wrist-based monitoring device (Fitbit Charge 2). Average steps/day were calculated for January 1 to February 13, 2020, and then weekly from February 14 to June 30. RESULTS: 42 patients were included. Their mean age was 55 years, 79% were males, and 69% were African Americans. Between January 1 and February 13, 2020, patients took on average 5,963 (95% CI 4,909-7,017) steps/day. In the week prior to the mandated lockdown, when a national emergency was declared, and in the week of the shutdown, the average number of daily steps had decreased by 868 steps/day (95% CI 213-1,722) and 1,222 steps/day (95% CI 668-2300), respectively. Six patients were diagnosed with COVID-19 during the study period. Five of them exhibited significantly higher PAL in the 2 weeks prior to showing COVID-19 symptoms compared to COVID-19 negative patients. CONCLUSION: Lockdown measures were associated with a significant decrease in PAL in hemodialysis patients. Patients who contracted COVID-19 had higher PAL during the incubation period. Methods to increase PAL while allowing for social distancing should be explored and implemented.