COVID-19 in dialysis: clinical impact, immune response, prevention, and treatment

Abstract

The COVID-19 pandemic has profound adverse effects on the population on dialysis. Patients requiring dialysis are at an increased risk of SARS-CoV-2 infection and mortality, and many have experienced psychological distress as well as delayed or suboptimal care. COVID-19 survivors have prolonged viral shedding, but generally develop a robust and long-lasting humoral immune response that correlates with initial disease severity. However, protection against reinfection is incomplete. A growing body of evidence reveals delayed and blunted immune responses to SARS-CoV-2 vaccination. Administration of a third dose within 1 to 2 months of prime-boost vaccination significantly increases antibody levels, in particular in patients with poor initial responses. Patients on dialysis have inferior immune responses to adenoviral vector vaccines than to mRNA vaccines. The immunogenicity of the mRNA-1273 vaccine is markedly better than that of the BNT162b2 vaccine, most likely by virtue of its higher mRNA content. Despite suboptimal immune responses in patients on dialysis, preliminary data suggest that vaccination partially protects against infection and severe disease requiring hospitalization. However, progressive waning of immunity and emergence of SARS-CoV-2 variants with a high potential of immune escape call for a booster dose in all patients on dialysis 4 to 6 months after prime-boost vaccination. Patients with persistent poor vaccine responses may be candidates for primary prophylaxis strategies. In the absence of specific data in patients on dialysis, therapeutic strategies in the event of established COVID-19 must be extrapolated from evidence obtained in the population not on dialysis. Neutralizing monoclonal antibodies may be an attractive option after a high-risk exposure or during the early course of infection.

Keywords: COVID-19; SARS-CoV-2; dialysis; hemodialysis; immune response; treatment; vaccination.

Figure 1

Immune response to infection and vaccination. Viral proteins are taken up by antigen presenting cells (APCs) that generate a range of pro-inflammatory cytokines. The antigens are presented to naive T cells that differentiate into different types of cells. T follicular helper (T_FH) cells assist B cells to differentiate into plasma cells that produce antigen-specific antibodies to neutralize the virus. A broad range of antibodies are generated against multiple epitopes on the spike protein, but those directed against the highly immunogenic receptor-binding domain appear to have the greatest neutralizing potential because they disrupt the interaction between the spike protein and the angiotensin II converting enzyme 2 receptor. Effector T cells destroy virus-infected cells. Macrophages phagocytose and digest antibody-tagged virus and virus-infected cells. Antigen-specific memory B and T cells develop to prevent future infection. In parallel with the serological response, antigen-specific memory B cells continuously acquire somatic mutations in their variable region genes to improve antigenic affinity. Upon antigenic reexposure, memory B cells drive the recall response by differentiating into high-affinity antibody-secreting plasma cells. Although antibody levels wane, antigen-specific memory B cells progressively become more numerous and mature.

Figure 2

Proposal for a vaccination strategy in patients on dialysis.^aAn adequate response to vaccination can be defined as antibody levels above a certain antibody threshold 4 weeks after vaccination, for example, 264 binding antibody units (BAUs)/ml. A low response can be defined by antibody levels >0 BAU/ml but <264 BAUs/ml. These thresholds need to be redefined for Delta and Omicron. The benefit of primary prophylaxis against variants of concern (VOCs) has not been demonstrated.