Immune responses to SARS-CoV-2 in dialysis and kidney transplantation

Abstract

Despite progressive improvements in the management of patients with coronavirus disease 2019 (COVID-19), individuals with end-stage kidney disease (ESKD) are still at high risk of infection-related complications. Although the risk of infection in these patients is comparable to that of the general population, their lower rate of response to vaccination is a matter of concern. When prevention strategies fail, infection is often severe. Comorbidities affecting patients on maintenance dialysis and kidney transplant recipients clearly account for the increased risk of severe COVID-19, while the role of uremia and chronic immunosuppression is less clear. Immune monitoring studies have identified differences in the innate and adaptive immune response against the virus that could contribute to the increased disease severity. In particular, individuals on dialysis show signs of T cell exhaustion that may impair antiviral response. Similar to kidney transplant recipients, antibody production in these patients occurs, but with delayed kinetics compared with the general population, leaving them more exposed to viral expansion during the early phases of infection. Overall, unique features of the immune response during COVID-19 in individuals with ESKD may occur with severe comorbidities affecting these individuals in explaining their poor outcomes.

Keywords: COVID-19; dialysis; infection; organ transplant.

FIGURE 1:

Schematic representation of the immune response to SARS-CoV-2. SARS-CoV-2 enters the epithelial host cells through endocytosis or membrane fusion after binding to the angiotensin-converting enzyme 2 (ACE2) receptor (1). Viral components are recognized by Toll-like receptors (2), whose downstream signaling promotes the secretion of type I and III IFNs and proinflammatory cytokines (3–5), which stimulate antigen-presenting cells and induce adaptive immunity. Adapted from ‘Acute Immune Responses to Coronaviruses’, BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.

FIGURE 2:

Immune responses to SARS-CoV-2 in dialysis patients and KTRs. Summary of immune alterations commonly observed in patients with COVID-19 (central panel) and derangements described in KTRs (left panel) and in patients on maintenance dialysis (right panel). Created with BioRender.com.