nfection with a pre-Omicron SARS-CoV-2 variant offered 35.5% protection against symptomatic Omicron BA.4 or BA.5 reinfection, while an Omicron infection was 76.2% protective, according to a Qatari test-negative, case-control study published yesterday in a letter to the New England Journal of Medicine.
The gap between the pre-Omicron infections and the BA.4/BA.5 reinfections were almost a year longer than the gap between the Omicron infections and BA.4/BA.5 reinfections, however, indicating that waning immunity played a role in protection against reinfections.
Led by researchers from Weill Cornell Medicine-Qatar in Doha, the team analyzed data on COVID-19 lab testing, clinical infection, vaccination, and demographic factors from an integrated nationwide digital-health information platform, which includes all results of polymerase-chain-reaction (PCR) and rapid antigen testing results from healthcare facilities.
The study spanned May 7 to Jul 28, 2022, a period of BA.4/BA.5 dominance in Qatar. The researchers said that Qatar has an unusually young and diverse population, with only 9% of its residents aged 50 years and older, and 89% expatriates from more than 150 countries. Each case-patient was matched with an uninfected control.
Protection waned over time
Pre-Omicron infection at least 90 days before reinfection was 35.5% (95% confidence interval [CI], 12.1% to 52.7%) effective against symptomatic BA.4/BA.5 reinfection and 27.7% (95% CI, 19.3% to 35.2%) effective against symptomatic or asymptomatic BA.4/BA.5 reinfection.
Omicron infection offered greater protection (76.2%; 95% CI, 66.4% to 83.1%) against symptomatic BA.4/BA.5 reinfection and 78.0% (95% CI, 75.0% to 80.7%) protection against symptomatic or asymptomatic infection.
Pre-Omicron infections occurred a median of 518 days before symptomatic BA.4/BA.5 infections, compared with a 189-day interval between the initial Omicron infection and the BA4/BA.5 reinfection—or a difference of 329 days. For any BA.4 or BA.5 reinfection, the difference was 309 days (490 vs 181).
Results were consistent in the different primary, sensitivity, and additional analyses. An analysis of effectiveness stratified according to time since previous infection revealed waning protection over time, and analyses classified by COVID-19 vaccination status suggested that previously infected vaccine recipients could have slightly higher protection against reinfection.
The study authors noted that BA.4 and BA.5 can escape neutralizing antibodies such as those conferred by previous infection or vaccination.
“Protection from a previous SARS-CoV-2 infection against BA.4 or BA.5 reinfection was modest when the previous infection had been caused by a pre-Omicron variant but strong when it had been caused by a post-omicron subvariant (including BA.1 or BA.2),” they wrote.
“Protection of a previous infection against reinfection with a BA.4 or BA.5 subvariant was lower than that against reinfection with a BA.1 or BA.2 subvariant because of more waning of immune protection over time and a greater capacity for immune-system evasion with the BA.4 and BA.5 subvariants,” they added.
The researchers cautioned that the study results may not generalize to other countries with an older population and said that the number of severe, critical, and fatal COVID-19 cases was too small to estimate the effectiveness of previous infection against hospitalization or death from reinfection.