Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

The initial efficacy of messenger RNA (mRNA) COVID-19 vaccines had high protection rates against infection and severe illness; however, as new variants developed and evidence of a waning immune response after vaccination became evident, vaccine efficacy diminished. This was particularly true during the Omicron surge of the pandemic. A study by Andrews and colleagues, which was published in the April 21, 2022 issue of the New England Journal of Medicine,^[1] addressed vaccine efficacy during the Omicron surge.

Researchers used national health databases in England for their study data, and their results included more than 2.5 million persons. At all time points, vaccine efficacy was stronger against the Delta vs Omicron variants. Vaccine efficacy against COVID-19 is also likely to be reduced among patients with chronic immunocompromising conditions. The current vaccine study by Andrews and colleagues focuses on patients undergoing hemodialysis.

Study Synopsis and Perspective

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford--AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, a multicenter observational study indicates.

After 2 doses of either vaccine, the risk for hospital admission was 75% lower among vaccinated patients whereas the risk for death was 88% lower compared with patients who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients older than age 65 years or with increasing time since vaccination, the authors added. The need for oxygen and ventilation was also halved among persons who had received 2 shots compared with persons who had not.

The study was published in the June 2022 issue of the Clinical Journal of the American Society of Nephrology.^[2]

"The [COVID-19] pandemic has had a devastating effect on the [chronic kidney disease (CKD)] community, particularly for individuals receiving maintenance dialysis," Matthew Oliver, MD, University of Toronto, Ontario, and Peter Blake, MD, Western University, London, Ontario, Canada, wrote in an accompanying editorial.^[3]

"Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes," they concluded.

Severe Outcomes Observed Less in Patients Who Tested Positive

The cohort included 1323 patients on hemodialysis who tested positive on polymerase chain reaction (PCR) testing for SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, Damien Ashby, MD, Hammersmith Hospital, London, United Kingdom, and colleagues reported.^[2]

Among persons who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators noted. Nearly a third (29%) of patients who tested positive required oxygen support, and 13% died before 28 days, they added. Among persons who died within 28 days of testing positive, 87% of the deaths were deemed to be caused by the virus itself.

"Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose," Ashby and colleagues emphasized.

"And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers," they added.

After vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy control participants.

In contrast, this was not the case for the Oxford--AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford--AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stressed.

They also noted that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem.

Although significant vulnerability in the dialysis population remains, "this population has much to gain from vaccination, regardless of age or vaccine type," the authors underscored.

As the editorialists pointed out,^[3] leaders in the CKD community were quick -- and successful -- in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, Canada, 90% of the maintenance dialysis population had received 2 doses of a COVID-19 vaccine by September 2021 and 78% had received 3 doses by January 2022.

Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-CoV-2 virus, as the editorialists noted.

The editorialists cautioned that the SARS-CoV-2 virus continues to mutate, and serology studies do show that vaccine-induced immunity does wane over time. Thus, although the COVID-19 pandemic is ever-changing, "we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population," Oliver and Blake recommended.

Commenting on the study,^[4] Uwe Korst from Bensheim, Germany, noted that COVID-19 is a daily reminder of how fragile life is for people with CKD.

"Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease," he wrote.

Thus, Korst continues to call for additional education for healthcare providers, patients, and the public to increase vaccine acceptance, shared decision making with patients, as well as more research to better understand the virus and its long-term consequences.

Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter and participating in advisory boards for Amgen Inc. and Janssen Pharmaceuticals, Inc. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Ashby and Korst have reported no relevant financial relationships.

Study Highlights

• The study sample was drawn from a national database of patients receiving hemodialysis in England. Patients receiving hemodialysis underwent weekly routine screening PCR tests for SARS-CoV-2 as well as PCR tests for any symptoms or fever.
• Patients receiving home dialysis or dialysis for a limited time only were not evaluated in the current study.
• The main study outcome was vaccine efficacy against COVID-19 across degrees of disease severity. The main study result was adjusted to account for demographic and disease variables as well as the time period when patients tested positive for SARS-CoV-2.
• There were ~ 5500 patients receiving hemodialysis in the study database, and SARS-CoV-2 was detected in 1323 patients (24% of sample). The median age of patients with SARS-CoV-2 infection was 62 years, and 60% were men. 38% of the cohort was Black; 32% was White; and 30% was classified as Asian/Other. 12% of the patient cohort was receiving immunosuppressive drugs.
• 79% of patients who tested positive for SARS-CoV-2 were unvaccinated. Most positive PCR samples were ordered for routine screening, not symptoms.
• 61% of patients positive for SARS-CoV-2 did not require admission; however, 29% required oxygen during their infection, and 13% died within 28 days of a positive test.
• The case-fatality rate attributable to COVID-19 was 11%. Variables associated with greater severity of COVID-19 included older age, diabetes, and the use of immune-suppressing drugs.
• One dose of COVID-19 vaccine was associated with a 45% (95% CI: 3, 69) reduction in the rate of admission.
• Vaccine efficacy against severe illness was most obvious among adults aged > 65 years.
• There was no difference in efficacy in comparing the BNT162b2 and AZD1222 (Oxford--AstraZeneca) vaccines. There was no waning of vaccine efficacy over time, although the observation period postvaccination lasted only 4 months.

 

Clinical Implications

• This previous study by Andrews and colleagues found that vaccine efficacy was stronger against the Delta vs Omicron variants at all evaluation points. Vaccine efficacy against Omicron infection for the BNT162b2 vaccine after 2 doses was 65.5% at 2 to 4 weeks after the application of the second dose, but the respective efficacy at ≥ 25 weeks after the second dose was just 8.8%; however, BNT162b2 efficacy against Omicron increased back to 62.4% at 2 to 4 weeks after a third booster dose. Booster efficacy waned to 45.7% at ≥ 10 weeks after dosing.
• The current study by Ashby and colleagues reveals a high (~ 24%) rate of positive tests for SARS-CoV-2 among patients undergoing hemodialysis earlier in the pandemic period. Nearly 40% of cases of COVID-19 in this cohort required hospital admission; however, vaccination with either 2 doses of BNT162b2 or AZD1222 reduced the risk for hospitalization for COVID-19 by 75%. Vaccine efficacy was most pronounced among older adults receiving hemodialysis.

Earn Credit