Among immunocompromised individuals vaccinated against COVID-19, solid organ transplant recipients as well as those with HIV and rheumatoid arthritis (RA) were significantly more likely to experience breakthrough infections versus people without immune dysfunction, a retrospective study found.
In a national database analysis involving over 650,000 people who received at least one vaccine dose, the highest breakthrough rates involved solid organ transplant recipients (adjusted incidence rate ratio [AIRR] 2.16, 95% CI 1.96-2.38), followed by people with HIV (AIRR 1.33, 95% CI 1.18-1.49) or RA (AIRR 1.20, 95% CI 1.09-1.32), reported Jing Sun, MD, MPH, PhD, of Johns Hopkins University in Baltimore, and colleagues.
“The findings support the use of alternative vaccine strategies (e.g., additional doses or immunogenicity testing) and nonpharmaceutical interventions (e.g., mask-wearing) even after full vaccination for people with immune dysfunction,” the group wrote in JAMA Network Open.
No significant increase in breakthrough infection rates were seen among people with multiple sclerosis (AIRR 1.12, 95% CI 0.93-1.35) or bone marrow transplant recipients (AIRR 1.09, 95% CI 0.85-1.40).
In an accompanying editorial, Alfred Kim, MD, PhD, of the Washington University School of Medicine in St. Louis, and Mary Nakamura, MD, of the San Francisco VA Health Care System, highlighted the study’s finding that disease severity and hospitalizations were decreased for vaccinated immunocompromised people with breakthrough infections versus immunocompromised individuals who contracted COVID-19 prior to vaccination.
Indeed, the analysis of the National COVID Cohort Collaborative (N3C) dataset revealed that severe outcomes among immunocompromised individuals occurred in 3.3% of those who had breakthrough cases, as compared with 6.3% of those during prevaccination periods.
“SARS-CoV-2 vaccines mitigated disease severity in individuals with immune suppression,” the editorialists wrote.
However, autoimmune patients receiving biologics, methotrexate, or corticosteroids may experience variable vaccine immunogenicity, Sun’s group cautioned.
“Recent research on patients who underwent solid organ transplant found that immunogenicity was substantially improved after a third dose of an mRNA vaccine (Pfizer-BioNTech), although it is unclear whether the enhanced antibody response will prevent a breakthrough infection,” added Kim and Nakamura.
For their current study, the researchers evaluated N3C data on 664,722 U.S. individuals who received at least one dose of an FDA authorized COVID-19 vaccine from Dec. 10, 2020 to Sept. 16, 2021, including 35,511 individuals with a known immune dysfunction condition. These included 13,445 RA patients, 2,970 multiple sclerosis patients, 8,536 people living with HIV, as well as 1,872 bone marrow transplant recipients and 8,688 solid organ transplant recipients. Overall, 59% of the cohort were white, 57% were female, and the average age was 51. About half of the individuals had comorbidities.
The rate of breakthrough infections among all fully vaccinated individuals in the cohort was 5 per 1,000 person-months, with the incidence rate (IR) increasing from 2.2 per 1,000 person-months (95% CI 2.2-2.2) during the pre-Delta period to 7.3 per 1,000 person-months (95% CI 7.3-7.4) during the Delta period starting in June 2021. Average time to breakthrough infection was 138 days, and breakthroughs tended to occur more frequently among women and older individuals.
Among those with immune conditions, IRs for breakthrough infections pre-Delta ranged from 2.6 per 1,000 person-months for bone marrow transplant recipients to 4.8 per 1,000 person-months for solid organ recipients; during Delta, these IRs ranged from 8.6 to 15.7 per 1,000 person-months for these transplant recipients, respectively.
Nearly all (91%) individuals in the overall cohort were fully vaccinated, which was associated with a 28% lower breakthrough infection risk compared to those who were only partially vaccinated (AIRR 0.72, 95% CI 0.68-0.76).
Poisson regression models used in the analysis adjusted for vaccination status, study period, location, demographics, and comorbidities.
The study had several limitations, the authors noted, including the use of electronic medical records data, which is prone to misclassification and underreporting vaccinations. Also, other conditions that can have a significant impact on the immune system, such as cancer, were excluded from the analysis.
Funding was provided by the National Center for Advancing Translational Sciences, the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, and the U.S. Department of Veterans Affairs.
Sun did not report any conflicts of interest. Coauthors reported various ties with industry.
Kim disclosed funding from Exagen Diagnostics, GlaxoSmithKline, Aurinia Pharmaceuticals, the NIH, Helmsley Charitable Trust, the National Institute of Arthritis, and the Rheumatology Research Foundation. Nakamura disclosed Moderna stock ownership.