Continuing research needed on COVID-19 vaccine in patients with kidney disease
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After conducting a systematic review of studies evaluating how patients with kidney disease respond to COVID-19 vaccines, investigators determined further research addressing specific limitations is required.
From the review, Edward J. Carr, MD, PhD, of the Francis Crick Institute in London, and colleagues also provided several recommendations to broaden understanding of how effective vaccination currently is for this patient population and how efficacy can be improved going forward.
“Early and rapid vaccination is an absolute priority for this at-risk group; however, although the results of vaccine trials have been impressive in the general population, the effectiveness of these vaccines has not been explicitly tested in patients with [chronic kidney disease] CKD, who are often excluded from trials,” Carr and colleagues wrote. “At present, clinical vaccine efficacy, immunogenicity, and persistence of protection are ‘known-unknowns’ in patients with CKD (including transplant recipients) and those with end-stage kidney disease (ESKD).”
Despite efforts by the international community to gather data on the immune response of patients with kidney disease, there are important limitations to consider, the researchers contended, writing: “Presently, the data available are heterogeneous, in early phases, and have been reported in different ways, which makes it difficult to make direct comparisons and provide quantitative synthesis.”
Varied response rates
The review included 35 studies with sample sizes ranging from 23 to 1,140 participants and follow-up ranging from 1 week to 1 month after vaccination.
In the studies of patients on dialysis who received an mRNA vaccine, antibody response varied with 18% to 53% of patients developing anti-SARS-CoV-2 antibodies after one dose and 70% to 96% developing antibodies after two doses.
“The development of anti–SARS-CoV-2 antibodies is variable and depends on several factors, including the time from vaccine administration to antibody measurement and type of antibody assay used,” the researchers wrote.
Differing response rates were also observed for transplant recipients, with 3% to 59% developing detectable humoral or cellular responses after two doses of mRNA vaccine.
Regarding concerns over reports of acute rejection following COVID-19 vaccination, Carr and colleagues recommend monitoring patients but also exercising caution when considering these reports.
“Although a causal link is difficult to prove on the basis of only [two] case reports so far, post-licensing surveillance will be crucial to monitor and confirm or refute a possible signal. In addition, at this time, transplant patients and health care workers must not delay in having the COVID-19 vaccination based on these sparse data,” they wrote. “The current data suggest there may be a diminished antibody response in this population, but maintenance immunosuppression must be maintained throughout the vaccination period and not reduced, as is being advocated in some patients with rheumatologic conditions who are on disease-modifying antirheumatic drugs. The risk-benefit ratio when weighed against acute rejection for patients with a kidney transplant is different from that of patients with rheumatologic diseases. Otherwise, the safety data on vaccination in transplant recipients has been reassuring based on [two] large case series, with mostly local reactions and no anaphylaxis or neurologic reactions.”
Limitations of available studies
Limitations that, according to Carr and colleagues are “common to all currently available studies” include the following:
- timing: “Most studies have reported antibody response early (the latest is 10 weeks after starting a vaccination course), and antibody response is at its most heterogeneous within these early weeks,” the researchers wrote;
- lack of surrogate measures of immunity and lack of comparison with control groups: “Once clinical trials are completed, antibody levels can be used as surrogate measures of vaccine efficacy; however, for the novel coronavirus SARS-CoV-2, there are as yet no internationally accepted standards defining what levels constitute immunity, and assays vary between laboratories,” Carr and colleagues wrote. “Therefore, interpretation of antibody levels requires direct experimental comparison with controls who are expected to have immunity — this can be healthy controls similar to those enrolled in the original trials of vaccine efficacy, or convalescent plasma from survivors of COVID-19 — and/or evaluation of viral neutralization. The majority of studies in our review did not compare the antibody responses to appropriate controls, used a variety of different assays to detect anti–SARS-CoV-2 antibodies, and did not measure viral neutralization or T-cell immunity, making interpretation of antibody levels difficult;” and
- lack of consideration for prior SARS-CoV-2 exposure: “Studies that do not measure, or report, baseline serostatus will be liable to comparing primary with secondary responders; this is a particular concern when comparing between studies, where the population prevalence of SARS-CoV-2 may be different.”
Ways to improve protection from COVID-19
With these limitations in mind, the researchers provided eight steps for optimizing vaccine efficacy, though they maintained these early data are useful for providing a “preliminary overview” of the protection patients with kidney disease might receive from vaccination and that encouraging vaccination is important. Recommendations included the following:
- conduct larger studies with standardized antibody platforms;
- consider routine clinical testing to monitor vaccine response;
- further investigations on the low immune response in transplant recipients;
- consideration how individuals who do not develop an antibody response may be protected from severe COVID-19;
- investigations on how to achieve vaccine efficacy in non-responders (through switching vaccine type or administering additional booster doses);
- determine the ideal assay for measuring antibody response;
- conduct serial measures of antibody levels; and
- understand vaccine efficacy in specific situations (the example given was response in patients with glomerulonephritis).
“In conclusion, the early data that describe the antibody response after vaccination against COVID suggest the response may be lower in patients with CKD compared with the general population; however (particularly for patients with CKD and those on dialysis), there are reasons to be optimistic that the response is robust for many,” the researchers wrote, adding that although transplant recipients and patients on immunosuppressive therapy may have a diminished response, vaccination still provides a “measurable effect.”
They added, “Larger data sets that measure antibody neutralization and outcome data after vaccination in all these patient groups are required to definitively establish vaccine effectiveness in patients with kidney disease and we strongly encourage international collaboration and data sharing between research groups toward this end.”
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