Post-vax COVID infection: What are the odds?

The odds of severe COVID-19 illness, hospitalization, and long COVID-19 were significantly reduced by more than half after two doses of vaccines compared with those unvaccinated, reveal data from a real-world study. Even if fully vaccinated people were infected, they were twice as likely to be completely asymptomatic than unvaccinated ones.

In addition, the population that was most susceptible to a breakthrough infection after the first dose of vaccine were older adults who were frail or who had pre-existing comorbid conditions such as heart disease, kidney disease, obesity, or lung disease. [Lancet Infect Dis 2021;doi:10.1016/S1473-3099(21)00460-6]

“We are at a critical point in the pandemic as we see cases rising worldwide due to the delta variant. Breakthrough infections are expected and don’t diminish the fact that these vaccines are doing exactly what they were designed to do — save lives and prevent serious illness,” said co-principal investigator Dr Claire Steves of King’s College London, London, UK.

The prospective, community-based, nested, case-control study collected data from more than 2 million UK-based, adult users of the COVID Symptom Study app, who self-reported on demographics, health risk factors, vaccination status, COVID-19 test results and symptoms. Cases were defined as testing positive for COVID-19 ≥14 days after the first vaccination (but before receiving the second dose) or testing positive ≥7 days after the second vaccine dose. Cases were matched 1:1 to unvaccinated controls who tested positive in the respective periods. The vaccines used were BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19.

Even if infections did occur post-vaccination, participants were almost three-quarter less likely to be hospitalized after the first (odds ratio [OR], 0.31; p<0.0001) and the second doses (OR, 0.27; p<0.0001) of vaccines compared with unvaccinated individuals.

After two doses of vaccines, the odds of developing long COVID (defined as having prolonged symptoms for ≥28 days) was halved compared with no vaccination (OR, 0.51; p=0.006).

Vaccinated people were also significantly less likely to develop severe disease — referring to >5 symptoms during the first week of COVID-19 illness — compared with unvaccinated individuals (OR, 0.74; p<0.0001 after the first dose and OR, 0.69; p=0.0180 after the second dose).  

“Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older,” noted Steves and co-authors.

Fully vaccinated recipients were twice as likely as those unvaccinated to be asymptomatic even if breakthrough infections occurred (OR, 1.94; p<0.0001). Moreover, the benefit of vaccination was particularly pronounced among older adults aged ≥60 years — who were more than twice as likely to be asymptomatic than their unvaccinated counterparts (OR, 2.38; p<0.0001).

“This increased incidence of asymptomatic or minimally symptomatic infection in vaccinated participants underlines the importance of individuals who interact with unvaccinated or clinically vulnerable groups (eg, healthcare workers and social care workers) continuing to regularly take tests for SARS-CoV-2, even if vaccinated,” the researchers pointed out.

Who is at risk?

While vaccination was protective against severe disease and hospitalization, there were certain characteristics which place one at increased risk to SARS-CoV-2 infection post-vaccination, particularly after only one vaccine dose.

Steves and team found that in older adults aged ≥60 years who were frail, the risk of contracting COVID-19 after one vaccine dose was nearly doubled compared with healthy older adults (OR, 1.93; p<0.0001).

Also, comorbidities such as kidney disease (OR, 1.95; p=0.014), heart disease (OR, 1.30; p=0.031), and lung disease (OR, 1.27; p=0.030) were risk factors associated with increased risk of infection following the first vaccine dose in older adults.

Across all age groups, people without obesity were less likely to contract infection post-vaccination than those who were obese (OR 0·84; p=0.003).

“To minimize SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated,” pointed out Steves and co-authors.

"Health policies designed to prevent infections, including policies around timing between the first and second dose and potential booster shots, should prioritize these groups,” said study co-author Dr Rose Penfold from King’s College, London, UK.