People with immune dysfunction who receive SARS-CoV-2 vaccination should be cautioned that they are at increased risk for breakthrough infection.

That's according to a new study from the National COVID Cohort Collaborative, a partnership that developed a secure, centralized electronic medical record–based repository of COVID-19 clinical data from academic medical centers across the United States.

In an article in JAMA Internal Medicine, the Johns Hopkins University Bloomberg School of Public Health–led authors found that patients with conditions such as HIV infection, rheumatoid arthritis, and solid organ transplant had a higher rate for COVID-19 breakthrough infection and worse outcomes after full or partial vaccination compared with vaccine recipients without immune dysfunction.

"The findings suggest that persons with immune dysfunction are at much higher risk for contracting a breakthrough infection and thus should use nonpharmaceutical interventions (e.g., mask wearing) and alternative vaccination approaches (e.g., additional dose or immunogenicity testing) even after full vaccination," the authors emphasize.

The study indicates that even though immune dysfunction patients have a higher risk for severe COVID-19 outcomes, they were generally excluded from SARS-CoV-2 vaccine clinical trials, which caused a significant evidence gap.

To remedy that, the study team sought to identify the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among those with or without immune dysfunction.

The retrospective cohort study analyzed data from 664,722 patients who received at least one dose of a SARS-CoV-2 vaccine between December 10, 2020, and September 16, 2021. The focus was on vaccination and COVID-19 diagnoses among those with immune dysfunction diagnoses, including HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, and bone marrow transplantation. Other comorbid conditions and demographic data also were considered.

For purposes of the study, breakthrough infection was defined as a COVID-19 infection that was contracted on or after the 14th day of vaccination. Participants (56.9% women) had a median age of 51 years.

Overall, results indicated that the incidence rate for COVID-19 breakthrough infection was 5.0 per 1,000 person-months among fully vaccinated persons but was higher after the Delta variant became the dominant SARS-CoV-2 strain (incidence rate before vs. after June 20, 2021, 2.2 [95% CI, 2.2-2.2] vs. 7.3 [95% CI, 7.3-7.4] per 1,000 person-months).

"Compared with partial vaccination, full vaccination was associated with a 28% reduced risk for breakthrough infection (adjusted IRR [AIRR], 0.72; 95% CI, 0.68-0.76)," the researchers advise. "People with a breakthrough infection after full vaccination were more likely to be older and women. People with HIV infection (AIRR, 1.33; 95% CI, 1.18-1.49), rheumatoid arthritis (AIRR, 1.20; 95% CI, 1.09-1.32), and solid organ transplant (AIRR, 2.16; 95% CI, 1.96-2.38) had a higher rate of breakthrough infection."

The study concludes that full vaccination was associated with reduced risk of COVID-19 breakthrough infection—and that was the case despite the immune status of patients. The researchers point out, however, "Despite full vaccination, persons with immune dysfunction had substantially higher risk for COVID-19 breakthrough infection than those without such a condition. For persons with immune dysfunction, continued use of nonpharmaceutical interventions (e.g., mask wearing) and alternative vaccine strategies (e.g., additional doses or immunogenicity testing) are recommended even after full vaccination."

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