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NPJ Vaccines ; 7(1):174, 2022.
Article in English | PubMed | ID: covidwho-2185871


Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

Nephrology Dialysis Transplantation ; 37(SUPPL 3):i357-i358, 2022.
Article in English | EMBASE | ID: covidwho-1915722


BACKGROUND AND AIMS: Patients on kidney replacement therapy (KRT) are at a particularly high risk of mortality from COVID-19. In this study, we investigated COVID-19 mortality in KRT patients in the first and second waves of the pandemic and potential reasons for any difference in mortality between the two waves. METHOD: Data from the European Renal Association COVID-19 Database (ERACODA) of KRT patients who presented between 1 March 2020 and 28 February 2021 with COVID-19 were analyzed. The cut-off for dividing the first and second waves was set for 1 August 2020. The primary study outcome was 28-day mortality. Multivariable Cox proportional-hazards regression analysis was used to examine the relationship between the pandemic waves and mortality with follow-up time starting at the date of presentation. Dialysis patients and kidney transplant recipients were analyzed separately. RESULTS: Among 3004 dialysis patients (1253 in the first and 1751 in the second wave), the 28-day mortality was 24.3% in the first wave and 19.6% in the second wave (P = .002). Compared with the first wave, in the second wave, identification of patients with limited to no symptoms was higher (14.3% versus 24.8%;P < .001), hospitalization was lower (71.3% versus 44.3%;P < .001), but in-hospital mortality was similar (30.4% versus 30.7%;P = .92) (Fig. 1). Crude hazard ratio (HR) for 28-day mortality in the second wave was 0.77 (95% CI: 0.66, 0.89). However, in a fully adjusted model, when correcting for differences in patient and disease characteristics, including the reason for COVID-19 screening and disease severity, the HR for mortality in the second wave was 0.93 [95% confidence interval (95% CI): 0.79-1.10]. When follow-up was chosen to start at the date of first symptoms to account for possible lead-time bias, crude HR for 28-day mortality in the second wave was 0.90 (95% CI: 0.75-1.07) and the fully adjusted HR was 0.98 (95% CI: 0.81-1.18). Among 1035 kidney transplant recipients (475 in the first and 560 in the second wave), results were essentially similar except that patients in the second wave were younger (55.6 years versus 58.2 years;P = .002), and crude HR for 28-day mortality from the date of first symptoms was 0.66 (95% CI: 0.47-0.93), whereas the fully adjusted HR was 1.02 (95% CI: 0.70-1.49). CONCLUSION: Among patients on KRT with COVID-19, 28-day mortality rates were lower in the second wave compared with the first wave. However, a greater proportion of patients with minimal symptoms, lead-time bias in dialysis patients, and younger age in kidney transplant recipients possibly explain the lower mortality during the second wave. Any improvement in patient management during the second wave may not be the main reason for lower mortality. (Table Presented).

Nephrology Dialysis Transplantation ; 36(SUPPL 1):i20, 2021.
Article in English | EMBASE | ID: covidwho-1402539


BACKGROUND AND AIMS: Patients on kidney replacement therapy (KRT) are at high risk of developing severe COVID-19 illness and often require high intensity care and utilisation of hospital resources. During the ongoing pandemic, the optimal care pathway and triage for KRT patients presenting with varying severity of COVID-19 illness is unknown. We studied clinical factors and outcomes associated with admission, readmission and short-term outcomes. METHOD: Data from the European Renal Association COVID-19 Database (ERACODA) was analysed. This database includes granular data on dialysis patients and kidney transplant recipients with COVID-19 from all over Europe. The clinical and laboratory features at first presentation of hospitalized and non-hospitalized patients and those who returned for second presentation were studied. In addition, possible predictors of outcome in those who were not hospitalized at first presentation were identified. RESULTS: Among 1,423 KRT patients (haemodialysis;1017/kidney transplant;406) with COVID-19, 25% (n=355) were not hospitalized at first presentation. Of them, only 10% (n=36), presented for a second time in the hospital. The median interval between the first and second presentation was 5 days (Interquartile interval: 2-7 days). Patients who re-presented had worsening of pulmonary symptoms, a fall in oxygen saturation (97% to 90%), and an increase in C-reactive protein (26 mg/L to 73 mg/L) between their attendances. Patients who re-presented after initial assessment were older (72 vs. 63 years) and initially more often had pulmonary symptoms and abnormalities on lung imaging compared with those who did not present for a second time. The 28-day mortality rate of patients admitted at the second presentation was similar to that of patients admitted at first presentation (26.5% vs. 29.7%, p=0. 61). Among patients who were not hospitalized at first presentation (mortality 6%), age, prior smoking, clinical frailty scale, and shortness of breath at first presentation were identified as predictors of mortality. CONCLUSION: KRT patients with COVID-19 and mild pulmonary abnormalities and no signs of pulmonary insufficiency can be safely returned without hospitalization. These patients should be advised to seek immediate contact when they develop respiratory distress. Our findings provide support for a risk-stratified clinical approach to admissions of KRT patients presenting with COVID-19. The study findings may be valuable for clinical triage and optimising hospital capacity utilisation during the ongoing pandemic.