COVID-19 vaccines less effective in immunocompromised people

Immunocompromised patients, particularly those who had undergone organ transplants, show markedly lower seroconversion rates after vaccination against the coronavirus disease 2019 (COVID-19), according to a recent Singapore meta-analysis.

“In organ transplant recipients, seroconversion remained severely reduced even after a second dose,” the researchers said. “These findings suggest that a third dose of COVID-19 vaccine would be efficacious in immunocompromised patients.”

A search through the online databases of PubMed, Embase, the Central Register of Controlled Trials, CORD-19, and the WHO COVID-19 database yielded 82 studies eligible for inclusion in this analysis. Most studies (94 percent) looked at mRNA vaccines, while 20 percent and 5 percent assessed viral vector and inactivated whole virus vaccines, respectively. All were prospective and observational in design.

Pooled analysis revealed significantly reduced seroconversion rates among immunocompromised patients after the first dose. For example, those with haematological malignancies were only 40 percent as likely as immunocompetent counterparts to show measurable titres of antibodies (risk ratio [RR], 0.40, 95 percent confidence interval [CI], 0.32–0.50). [BMJ 2022;376:e068632]

Similarly, those with immune-mediated inflammatory disorders (RR, 0.53, 95 percent CI, 0.39–0.71) and solid cancers (RR, 0.55, 95 percent CI, 0.46–0.65) were about half as likely to seroconvert.

Notably, organ transplant recipients saw the worst outcome and were nearly 95 percent less likely to reach seroconversion than immunocompetent individuals after the first vaccine dose (RR, 0.06, 95 percent CI, 0.04–0.09).

Even after the second vaccine dose, organ transplant recipients were the least likely to display a detectable antibody response, with only around a third of patients achieving seroconversion (RR, 0.39, 95 percent CI, 0.32–0.46).

Likewise, the second dose led to slight improvements in seroconversion rates among those with haematological cancers (RR, 0.63, 95 percent CI, 0.57–0.69), solid cancers (RR, 0.90, 95 percent CI, 0.88–0.93), and immune-mediated inflammatory disorders (RR, 0.75, 95 percent CI, 0.69–0.82), though such likelihood remained significantly reduced overall.

In contrast, persons living with HIV did not suffer from significantly suppressed seroconversion rates relative to immunocompetent counterparts (RR, 1.00, 95 percent CI, 0.98–1.01).

“Our meta-analyses suggest significant heterogeneity in immunogenicity between different immunocompromised groups, after both the first and the second dose of COVID-19 vaccines,” the researchers said. “Vaccine regimes may need to be tailored according to the cause and degree of immunocompromise.”

“Additional strategies, such as the administration of a third vaccine dose to the conventional two dose regimen for mRNA covid-19 vaccines would be warranted to confer improved seroprotection for these patients,” they added.