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.

Sample pooling: burden or solution?

BACKGROUND: Pool-testing strategies combine samples from multiple people and test them as a group. A pool-testing approach may shorten the screening time and increase the test rate during times of limited test availability and inadequate reporting speed. Pool testing has been effectively used for a wide variety of infectious disease screening settings. Historically, it originated from serological testing in syphilis. During the current coronavirus disease 2019 (COVID-19) pandemic, pool testing is considered across the globe to inform opening strategies and to monitor infection rates after the implementation of interventions. AIMS: This narrative review aims to provide a comprehensive overview of the global efforts to implement pool testing, specifically for COVID-19 screening. SOURCES: Data were retrieved from a detailed search for peer-reviewed articles and preprint reports using Medline/PubMed, medRxiv, Web of Science, and Google up to 21st March 2021, using search terms "pool testing", "viral", "serum", "SARS-CoV-2" and "COVID-19". CONTENT: This review summarizes the history and theory of pool testing. We identified numerous peer-reviewed articles that describe specific details and practical implementation of pool testing. Successful examples as well as limitations of pool testing, in general and specifically related to the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies, are reviewed. While promising, significant operational, pre-analytical, logistical, and economic challenges need to be overcome to advance pool testing. IMPLICATIONS: The theory of pool testing is well understood and numerous successful examples from the past are available. Operationalization of pool testing requires sophisticated processes that can be adapted to the local medical circumstances. Special attention needs to be paid to sample collection, sample pooling, and strategies to avoid re-sampling.