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.

Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes where it counteracts hypercalcemia by inhibiting gill calcium uptake and stimulating renal inorganic phosphate (P i ) reabsorption. Human STC (hSTC) has recently been cloned and sequenced and is highly homologous to the fish hormone at the amino acid level. The objective of this study was to examine the possible effects of hSTC on electrolyte homeostasis and renal function in the rat. Recombinant hSTC was expressed in bacteria and purified by metal-ion affinity chromatography and reverse-phase high performance liquid chromatography. Anesthetized animals were given bolus infusions of 1, 5, or 10 nmol hSTC per kilogram of body weight. Control animals received solvent alone. The most effective dosage was 5 nmol/kg, which caused significant reductions in both absolute and fractional phosphate excretion in comparison with control rats. The hSTC had no effect on the renal excretion of other ions, the glomerular filtration rate, renal blood flow, blood pressure, or plasma electrolytes (Na

Stanniocalcin (STC) is a homodimeric glycoprotein hormone that was first discovered in fish, where it is produced by unique endocrine glands known as the corpuscles of Stannius (CS). In freshwater salmon, STC plays an integral role in Ca2+ and phosphate homeostasis. High levels of extracellular Ca2+promote the synthesis and release of STC, which on entering the bloodstream reduces the levels of gill and gut Ca2+ transport and renal phosphate excretion to restore normocalcemia. In this report, we have examined STC in seawater salmon. We have studied the distribution of STC protein and mRNA in marine Atlantic salmon CS cells, the responsiveness of these cells to Ca2+, and some physical properties of the hormone. Our results demonstrated that all Atlantic salmon CS cells expressed the STC gene. Furthermore, these cells exhibited a Ca2+ sensitivity that was remarkably similar to those in freshwater salmon in terms of its ability to stimulate STC secretion and gene expression. When Atlantic salmon glands were fractionated by concanavalin A (ConA)-Sepharose chromatography, two distinct forms of the hormone were identified, both of which were recognized by sockeye salmon STC antiserum, and designated as STC1 and STC2. STC1 was a glycosylated, 42-kDa disulfide-linked dimer, with a high affinity for ConA. STC2 did not bind to ConA, was 44 kDa in size, and had a different subunit structure. STC2 was also a less effective inhibitor of gill Ca2+ transport in fish. Collectively, the results suggest that there is a second form of STC in salmon.

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