Therapeutic Drug Monitoring of Mycophenolic Acid Identifies Kidney Transplant Recipients Responsive to Two SARS-CoV-2 mRNA Vaccine Doses.

Immune-responsiveness to SARS-CoV-2 mRNA vaccination is reduced in kidney transplant recipients (KTRs). Previous reports point to a role of mycophenolic acid (MPA). Our observational cohort study included all KTRs at University Hospital Zurich receiving two SARS-CoV-2 mRNA vaccine doses more than 6 months post-transplantation, who were assessed by measuring anti-spike immunoglobulin G (IgG). We applied principles of therapeutic drug monitoring (TDM) to correlate MPA exposure and lymphocyte counts with SARS-CoV-2 IgG. MPA trough levels differ largely among KTRs with a median of 3.1 mg/L (range 0.7-9.5 mg/L). 34 of 84 KTRs (40%) developed positive SARS-CoV-2 IgG after two vaccine doses. KTRs who developed positive SARS-CoV-2 IgG showed significantly higher eGFR (p < 0.001), lower MPA trough levels (p < 0.001) and higher CD19+ lymphocytes (p < 0.001). MPA trough levels <2.5 mg/l and CD19+ lymphocytes >40/µl identify KTRs with seroconversion. Upon logistic regression, MPA trough levels <2.5 mg/L were associated with a 7-fold (CI 95%: 1.589-29.934) and ciclosporin use with a 6-fold (CI 95%: 1.148-30.853) increase in the odds of seroconversion. Our study indicates that immune-responsiveness to SARS-CoV-2 mRNA vaccines correlates with MPA exposure measured by MPA trough level but argues against a class effect of MPA. TDM-guided MPA dosing may be a strategy to increase seroconversion rate.

Insights into the challenges faced by chronically critically ill patients, their families and healthcare providers: An interpretive description.

OBJECTIVE: To describe and understand the challenges of patients with chronic critical illness (CCI), their families and healthcare providers during the disease trajectory. METHODOLOGY/DESIGN: This qualitative study follows Thorne's methodology of interpretive description and was guided by the ethnographic method of observation and participation. Five cases, each comprising one patient with chronic critical illness their family members and several healthcare providers, were followed from the intensive care unit of a university hospital in Switzerland across different settings. In total, five patients with chronic critical illness, 12 family members and 92 healthcare providers (nurses, nursing students, care assistants, physiotherapists and occupational therapists and physicians) were observed. FINDINGS: Regardless of the medical diagnoses and disease trajectories of the patients with chronic critical illness, all cases faced three main challenges: 1. Dealing with the unpredictability of the disease trajectory beyond the underlying disease. 2. Coping with the complexity of care. 3. Perceiving communication challenges despite all involved parties' dependency on it. CONCLUSION: Unpredictability is not only a unique characteristic of the prolonged disease trajectory of patients with chronic critical illness, but also one of the main challenges of the participants. Therefore, the way unpredictability is handled is dependent on changes in the complexity of care and communication, highlighting the need for participation, information, empathy, clarity and honesty among all participants.