RESUMO
BackgroundHemodialysis patients are exposed to a markedly increased risk when infected with SARS-CoV-2. To date it is unclear if hemodialysis patients benefit from a fourth vaccination. MethodsA total of 142 hemodialysis patients (median age 72.6 years, 33.8% female) received four COVID-19 vaccinations between December 2020 and March 2022. RDB binding antibody titers were determined in a competitive surrogate neutralization assay. Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC) Delta (B.1.617.2) or Omicron (B.1.1.529, sub lineage BA.1) in a biosafety level 3 laboratory to determine serum infection neutralization capacity before and after vaccination. ResultsAfter the fourth vaccination serum infection neutralization capacity significantly increased from a 50% inhibitory concentration (IC50, serum dilution factor 1:x) of 247.0 (46.3-1560.8) to 2560.0 (1174.0-2560.0) for the Delta VoC, and from 37.5 (20.0-198.8) to 668.5 (182.2-2560.0) for the Omicron VoC (each p<0.001). A significant increase of the neutralization capacity was even observed for patients who had high antibody titers after three vaccinations (p<0.001). Univariate regression analysis indicated immunosuppressive medication (p=0.001) and hepatitis B vaccination non-response (p=0.046), and multivariate analysis immunosuppressive medication as the only factor associated with a reduced effect against Delta (p<0.001). Ten patients with SARS-CoV-2 breakthrough infection before the fourth vaccination had by trend lower prior neutralization capacity for Omicron (p=0.051). ConclusionsOur findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron variant. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients.
RESUMO
Acute kidney injury is a clinical syndrome that can be caused by numerous diseases including acute tubular necrosis (ATN). ATN evolves in several phases, all of which are accompanied by different immune mechanisms as an integral component of the disease process. In the early injury phase, regulated necrosis, damage-associated molecular patterns, danger sensing, and neutrophil-driven sterile inflammation enhance each other and contribute to the crescendo of necroinflammation and tissue injury. In the late injury phase, renal dysfunction becomes clinically apparent, and M1 macrophage-driven sterile inflammation contributes to ongoing necroinflammation and renal dysfunction. In the recovery phase, M2-macrophages and anti-inflammatory mediators counteract the inflammatory process, and compensatory remnant nephron and cell hypertrophy promote an early functional recovery of renal function, while some tubules are still badly injured and necrotic material is removed by phagocytes. The resolution of inflammation is required to promote the intrinsic regenerative capacity of tubules to replace at least some of the necrotic cells. Several immune mechanisms support this wound-healing-like re-epithelialization process. Similar to wound healing, this response is associated with mesenchymal healing, with a profound immune cell contribution in terms of collagen production and secretion of profibrotic mediators. These and numerous other factors determine whether, in the chronic phase, persistent loss of nephrons and hyperfunction of remnant nephrons will result in stable renal function or progress to decline of renal function such as progressive chronic kidney disease.
