The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

BackgroundThe overall incidence of Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients is 5–15%. A timely diagnosis of PJP is difficult and relies on imaging and detection of the organism.MethodsWe present a case series of four patients displaying hypercalcaemia with an eventual diagnosis of PJP and document the management of the outbreak with a multidisciplinary team approach. We discuss the underlying pathophysiology and previous reports of hypercalcaemia preceding a diagnosis of PJP. We also reviewed the evidence concerning PJP diagnosis and treatment.ResultsWithin our renal transplant cohort, four patients presented within 7 months with hypercalcaemia followed by an eventual diagnosis of PJP. We measured their corrected calcium, parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 25-hydroxycholecalciferol [25(OH)D] levels at admission and following treatment of PJP. All four patients diagnosed with PJP were 4–20 years post-transplantation. Three of the four patients demonstrated PTH-independent hypercalcaemia (corrected calcium >3.0 mmol/L). The presence of high 1,25(OH)2D3 and low 25(OH)D levels suggest negation of the negative feedback mechanism possibly due to an extrarenal source; in this case, the alveolar macrophages. All four patients had resolution of their hypercalcaemia after treatment of PJP.ConclusionsGiven the outbreak of PJP in our renal transplant cohort, and based on previous experience from other units nationally, we implemented cohort-wide prophylaxis with trimethoprim–sulphamethoxazole for 12 months in consultation with our local infectious diseases unit. Within this period there have been no further local cases of PJP.

Clinicians should consider numerous factors to predict the probability of and timing to pleurodesis with tunnelled pleural catheters.

Kidney transplant recipients undergo lifelong monitoring of allograft function and evaluation for transplant complications. The current monitoring paradigm utilizes blood, urine, and tissue markers that are insensitive, nonspecific, or invasive to obtain. As a result, problems are detected late, after significant damage has accrued, and often beyond the time at which complete resolution is possible. Indeed, most kidney transplants eventually fail, usually because of chronic rejection and other undetected injury. There is a clear need for a transplant-specific biomarker that enables a proactive approach to monitoring via early detection of reversible pathology. A biomarker that supports timely and personalized treatment would assist in achieving the ultimate goal of improving allograft survival and limiting therapeutic toxicity to the recipient. Donor-derived cell-free DNA (ddcfDNA) has been proposed as one such transplant biomarker. Although the test is presently utilized most in the United States, it is conceivable that its use will become more widespread. This review covers aspects of ddcfDNA that support informed use of the test by general nephrologists, including the basic biology of ddcfDNA, methodological nuances of testing, and general recommendations for use in the kidney transplant population. Clinical contexts are used to illustrate evidence-supported interpretation of ddcfDNA results and subsequent management. Finally, knowledge gaps and areas for further study are discussed.