ABSTRACT
BACKGROUND AND AIMS: Previous data has shown a reduced immune response shortly after SARS-CoV-2 vaccinations in haemodialysis patients. We therefore investigated the long-term antibody response in patients from different outpatient dialysis centres at 4 weeks and 6 months after a complete vaccination against COVID-19. The results were compared with the humoral responses of non-dialysis subjects. METHODS: We designed a retrospective multicentric cohort study, enrolling 106 haemodialysis patients and 50 non-dialysis patients after the SARS-CoV-2 vaccination. SARS-CoV-2 antibody testing was performed as part of routine clinical practice 4 weeks as well as 6 months after the immunization with chemiluminescence immunoassays designed to detect antibodies against the SARS-CoV-2 spike protein (Elecsys Anti-SARS-CoV-2 S, Roche Diagnostics, Mannheim, Germany). Testing was performed in the Institute of Laboratory Medicine of the University Hospital Munich. According to the manufacturer's specifications, anti-SARS-CoV-2 S titres >0.8 U/mL are considered reactive (sensitivity 98.8% and specificity 99.9%). Anti-SARS-CoV-2 S titres < 100 U/mL were defined as a low antibody response. RESULTS: A total of 106 haemodialysis patients with a median age of 73 years received a SARS-CoV-2 vaccination (n = 105 mRNA, n = 1 AstraZeneca). Of these, 50 non-dialysis patients with a median age of 56 years received a SARS-CoV-2 vaccination (n = 45 mRNA, n = 5 mRNA/AstraZeneca). During the observational period, 8 haemodialysis patients and 2 non-dialysis patients additionally contracted a SARS-CoV-2 infection. Between the two testings, an overall decrease in anti-SARS-CoV-2 S antibody titres was observed (haemodialysis patients from a median of 252 to 95 U/mL, nondialysis patients from a median of 1621 to 441 U/mL). At 6 months after the complete vaccination, 99 (93%) haemodialysis patients still presented with a detectable anti-SARS-CoV-2 spike antibody response (>0.8 U/mL), comparable to 100% of the non-dialysis subjects. However, 60 (57%) haemodialysis patients showed low antibody response (<100 U/mL), whereas only 5 (10%) non-dialysis patients presented with low antibody response. Patients with an additional infection showed an increased titre of antibodies during follow-up. CONCLUSIONS: Our data suggest regular antibody testing as well as a need for booster vaccination in the vulnerable population of haemodialysis patients.
ABSTRACT
Introduction: TDM of immunosuppressive drugs, e.g. tacrolimus, is an integral part of transplantation medicine. Critical dose drugs require regular monitoring to prevent graft rejection (underdosage) and severe adverse events including nephro-, cardiac or neurotoxicity (overdosage). Current standards for laboratory medical monitoring of transplant patients require venous blood sampling. This collection step is time-consuming and costly. Additionally, it involves a clinic visit. In contrast, capillary blood samples can be obtained by the patient and sent to the laboratory. Thus, CMS may facilitate TDM e.g. during the COVID-19 pandemic. Here we establish TDM of tacrolimus from CMS in order to increase the efficiency and outsource TDM of transplant patients. Methods: Simultaneously collected venous and capillary blood was used as sample material. CMS was carried out by using a volumetric absorption microsampling device (VAMS) called Mitra (Neoteryx®, Torrance, CA). Laboratory analysis for tacrolimus was performed by a LC-MS/MS method, which has been established as routine in our laboratory for 20 years. Results: Using capillary blood simplifies collection of material for TDM. Mitra VAMS standardize volume and allow shipment. Preliminary investigations of six renal transplant recipients comparing venous and capillary blood samples showed similar drug concentrations of tacrolimus (recovery 93.6% to 105.8%, figure). Percentage error was in an acceptable limit of -7.4% to 5.8% (mean percentage error of 4.1%). Additionally, a stability up to three weeks could be shown. Conclusion: The use of capillary blood to perform TDM of tacrolimus leads to a significant improvement of the aftercare monitoring of transplant recipients. This enables a less invasive method, patient self-sampling from home and forward material to a specialized laboratory. Therefore, transplant patients can reduce visits to the clinic.
ABSTRACT
Introduction: Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. The specific features of coronavirus disease 2019 (COVID-19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Methods: Seven transplanted patients (two liver, three kidney, one double lung, one heart) admitted to the Ludwig-Maximilians-University Munich because of COVID-19 and tested positive for SARS-CoV-2 were included. The clinical course and the clinical findings were extracted from the medical record. Transplanted patients admitted to the ICU were compared to immunocompetent patients admitted to the ICU (n=19). Results: The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18 and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours after admission. Weaning could be initiated in these patients after 16 and 19 days of mechanical ventilation, respectively. One kidney and the lung transplant recipients were required to be intubated after ten and 15 days, respectively. This kidney recipient was discharged in good health after 17 days. Thus, only the lung transplant recipient is on mechanical ventilation. Immunosuppression was adapted in five patients, but continued in all patients. Target trough levels were evaluated regularly and were within range during hospital stay. No graft loss or death was documented. Compared to non-transplanted patients the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL-6 and LDH blood values. Conclusion: This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS-CoV-2, their clinical course seems to be similar to immunocompetent patients.
ABSTRACT
Introduction: Chronic dialysis represents a state of immunocompromise. Unlike the general population, patients cannot observe strict isolation as they have to visit the dialysis unit three times per week and therefore potentially increase their risk of contracting an infection with SARS-CoV-2. This represents a special dilemma for patients awaiting renal transplantation. Active infection is considered a contraindication whereas renal transplantation may be considered for dialysis patients who have recovered. Methods: Referring dialysis physicians were surveyed to report non-transplantable and SARS-CoV-2 infected patients. The incidence of PCR-confirmed SARS-CoV-2 cases among dialysis patients on the kidney transplant waiting list was compared with a non-matched population in the referral area (Bavaria). Results: As of May 1st 2020, 42,489 individuals of the general population (0.33%) in Bavaria had been infected with SARS-CoV-2. At the same time, 4 out of 331 patients (1.3 %) on our waiting list contracted an infection with SARS-CoV-2. 2 were asymptomatic, one required inpatient treatment. None died due to COVID-19. 313 patients were without clinical signs of SARS-CoV-2 infection. Thereof 60 were also negative on PCR-testing due to infection in the respective centre. 5 patients had died during the pandemic due to non-COVID-19 related causes. For 18 patients no information on SARS-CoV-2 was available. Thus, patients on the renal transplant waiting list had a 3.9-fold higher incidence of SARS-CoV-2 infection (p=0.02). Conclusion: Although epidemiological statements based on this survey are deemed uncertain, the incidence of symptomatic SARS-CoV-2 infections in dialysis patients on the waiting list seems to be slightly higher. The absolute numbers are low, however, and the observed courses of disease are mild.