Weak immune systems tied to more COVID-19 breakthrough infections

Cancer patient on oxygen
Cancer patient on oxygen

Evgeniy Shkolenko / iStock

While COVID-19 breakthrough infections—cases after vaccination—are rare, fully vaccinated people with compromised immune systems have them three times more often than those with strong immune systems and have more severe illnesses, according to a real-world US study involving nearly 1.3 million people.

In the retrospective study, published today in the Journal of Medical Economics, a team led by researchers from Pfizer analyzed the health records of 1,277,747 people aged 16 or older who had received two doses of the Pfizer/BioNTech COVID-19 vaccine from Dec 10, 2020, to Jul 8, 2021. The latter part of the study period included the emergence of the Delta (B1617.2) variant in the United States.

Rare but severe infections

Of all people studied, 17.7% were immunocompromised by conditions such as solid tumor (32.0%), kidney disease (19.5%), and rheumatologic/inflammatory conditions (16.7%). Median patient age in this cohort was 58 years, with 48.3% from 50 to 64 years and 23.0% 65 and older; 56.3% were female, and 74.5% had health insurance.

Nearly two thirds (62.5%) of this group had at least one underlying condition that put them at risk for severe COVID-19, versus 19.3% of those who were not immunocompromised. The most common of these conditions were obesity (9.4%), type 2 diabetes (9.2%), smoking (5.4%), and cancer (5.2%).

Among patients with healthy immune systems, 53.1% were female and 80.2% had commercial health coverage; median age was 45 years, with 33.3% from 50 to 64 years and 9.3% 65 and older.

While only 978 of 1,176,907 people (0.08%) who had received their second dose of COVID-19 vaccine at least 2 weeks before had a breakthrough infection, people with weakened immune systems accounted for upwards of 38% of infections, 60% of hospitalizations, and both deaths.

Of all vaccinated people with breakthrough cases, 97.1% had a clinic visit and 12.7% required hospital admission, 59.7% of whom had weakened immune systems. The share of people with breakthrough infections was three times higher among immunocompromised vaccinees (0.18%) than among the non-immunocompromised (0.06%), though the risk was very small for both groups.

Findings support booster doses

Organ transplant recipients had the highest rate of breakthrough infections. Patients with more than one immunocompromising (IC) condition and those who used antimetabolite cancer drugs or had primary immunodeficiencies or blood cancer had higher breakthrough rates than other patients with weakened immune systems.

Incidence rates in patients 65 years and older were higher than those among their younger counterparts.

"While some COVID-19 vaccine breakthrough infections among those who are fully vaccinated against COVID-19 are expected, the findings of this study show that they are rare and less likely to result in hospitalization or death in those without an IC condition," the authors wrote. "However, further research is necessary to continue monitoring the rates of breakthrough infections in the general population, especially with waning duration of protection and emerging SARS-CoV-2 variants."

Lead study author Manuela Di Fusco, MS, director of health economics and outcomes research at Pfizer, said in a Taylor & Francis Group press release that the results support the use of booster COVID-19 vaccine doses.

"Several countries are currently experiencing a resurgence of SARS-CoV-2 infections despite the rollout of mass vaccination programmes," she said. "While COVID-19 mRNA vaccines help protect people from getting infected and severely ill, the risk of breakthrough infections in fully vaccinated people is not completely eliminated."

Di Fusco added that although the study used a large dataset that has been used in previous US research, its limitations include coding accuracy and data representativeness after the study period.

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