Severe COVID-19: Who is at risk even after full vax?

Individuals with risk factors such as pre-existing comorbid conditions, in addition to old age and being immunosuppressed, may still be at increased risk of developing severe COVID-19 illness even after completing their full vaccination, according to a study by the US CDC. 

After primary vaccination, the odds of having severe COVID-19 outcomes were approximately threefold higher in the elderly aged ≥65 years (adjusted odds ratio [aOR], 3.22, 95 percent confidence interval [CI], 1.81–5.74) and twofold greater in those who were immunosuppressed (aOR, 1.91, 95 percent CI, 1.37–2.66). [medrxiv 2022;doi:10.1101/2021.07.08.21259776v1]

Underlying comorbid conditions such as cardiac disease (aOR, 1.44, 95 percent CI, 1.01–2.06), diabetes (aOR, 1.47, 95 percent CI, 1.14–1.89), neurologic disease (aOR, 1.54, 95 percent CI, 1.06–2.25), chronic kidney disease (aOR, 1.61, 95 percent CI, 1.19–2.19), liver disease (aOR, 1.68, 95 percent CI, 1.12–2.52), and pulmonary disease (aOR, 1.69, 95 percent CI, 1.31–2.18) were also associated with increased risk of severe COVID-19 despite full vaccination.

On the other hand, individuals who had COVID-19 previously were less likely to have severe outcomes from subsequent infection after vaccination (aOR, 0.27, 95 percent CI, 0.09–0.84).

“Severe COVID-19 out­comes after primary vaccination are rare; however, vaccinated persons who are aged ≥65 years, are immunosuppressed, or have other underlying conditions might be at increased risk,” the researchers stated. 

“Even when vaccinated, persons with identifiable risk factors should receive interventions including chronic disease management, precautions to reduce exposure, additional primary and booster vaccine doses, and effective pharmaceutical therapy as indicated to reduce risk for severe COVID-19–associated outcomes,” they urged. “Increasing COVID-19 vaccination coverage is a public health priority.”

Among 1,228,664 fully vaccinated participants, 2,246 had COVID-19, of which 189 had developed severe outcomes — referring to hospitalization with acute respiratory failure or noninvasive ventilation (NIV; 5.7 percent), admission to intensive care unit (ICU; 1.1 percent), or death (1.6 percent). 

All patients who went on to develop severe outcomes despite full vaccination had at least one risk factor mentioned above. Their risk of such outcomes grew with increasing number of risk factors shown.

The majority of patients (78 percent) who died had at least four risk factors.

Participants in the study were 1,228,664 adults (57.6 percent female) who had completed primary vaccination (those who had boosters were also included) across 465 facilities in the US under the Premier Healthcare Database Special COVID-19 Release (PHD-SR). Most of the participants received mRNA-based vaccines (72.8 percent Pfizer-BioNTech and 20.0 percent Moderna).

Compared with recipients of the Janssen vaccine (6.5 percent), the odds of developing severe COVID-19 were comparable with those who received the Pfizer-BioNTech vaccine (aOR, 0.70, 95 percent CI, 0.39–1.26), while the odds were lower in those who were given the Moderna vaccine (aOR, 0.56, 95 percent CI, 0.32–0.98).

“This study provides insight into the frequency of and risk factors for severe outcomes among persons who acquired COVID-19 after primary vaccination during periods of pre-Delta and Delta variant predominance; [the] findings might not be applicable to the risk from SARS-CoV-2 B.1.1.529 (Omicron) variant or future variants,” the researchers pointed out.

“With the emergence of novel variants of concern and development of additional therapeutic strategies, studies in vaccinated populations are vital to guide targeted guidelines and interventions for persons at risk for severe outcomes,” they suggested.