Risk of COVID-19 Breakthrough Infection Heightened for Immunocompromised


People with immune dysfunction are at increased risk for COVID-19 breakthrough infection after vaccination, and should take additional precautions.

People with immune dysfunction are at increased risk for COVID-19 breakthrough infection after vaccination, as compared to persons who are not immunocompromised.

Immunocompromised people are at increased risk of severe or fatal COVID-19 disease. This vulnerability meant people with immune dysfunction were prioritized during the initial COVID-19 vaccine rollout, but they were largely excluded from vaccine trials.

The lack of evidence of the efficacy of COVID-19 vaccination in immunocompromised persons means little is known of the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infections after vaccination among people with immune dysfunction.

A recent study, published in JAMA Internal Medicine, researched whether immunocompromised persons had a higher rate of COVID-19 breakthrough infection after full or partial vaccination.

The retrospective cohort study included 664722 immunocompromised patients who received at least 1 dose of a COVID-19 vaccine between December 10, 2020-September 16, 2021. The participants had an average age of 51 years, and were 56.9% female.

The investigators analyzed data from the National COVID Cohort Collaborative (N3C), a repository of COVID-19 clinical data from US academic medical centers. Available data included vaccination status, COVID-19 diagnosis, immune dysfunction diagnoses (e.g., HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, bone marrow transplantation), other comorbidities, and demographic data.

The investigators used Poisson regression models to assess the risk of breakthrough infection after full of partial COVID-19 vaccination. “Breakthrough infection” was defined as contracting COVID-19 on or after the fourteenth day of vaccination. Poisson regression was controlled for study period (before or after the emergence of the Delta variant), full vaccination status, COVID-19 infection before vaccination, demographic characteristics, geographic location, and existing comorbidities.

The results showed that people with immune dysfunction are at significantly higher risk for COVID-19 breakthrough infection after vaccination, as compared to people who are not immunocompromised. The breakthrough infection incidence rate was 5.0/100 person-months among fully vaccinated individuals, but increased after Delta became the dominant variant.

Fully vaccinated persons had a 28% reduced risk for breakthrough infection. People living with HIV, rheumatoid arthritis, and solid organ transplant were more likely to experience breakthrough infections. Breakthrough infections were also most common among woman and older persons.

The investigators stressed the importance of nonpharmaceutical interventions, like mask wearing and social distancing, for people with immune dysfunction. Additionally, they recommended immunocompromised people consider immunogenicity testing and an additional dose of a COVID-19 vaccine.

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