How Vaccine Immunity, Prior Infection Hold Up Against BA.2

Protection against symptomatic BA.1 or BA.2 COVID-19 infection was similar between individuals who received three doses of an mRNA vaccine and those who had either a prior infection or some form of hybrid immunity, a national case-control study from Qatar found.

Against severe disease from either of the two Omicron subvariants, effectiveness was strong across the different types of immunity, at 70% or higher, reported Laith Abu-Raddad, PhD, of Weill Cornell Medicine-Qatar in Doha, and colleagues in the New England Journal of Medicine.

For example, effectiveness against a symptomatic case of BA.2 — the dominant U.S. strain until early May (BA.2.12.1 now makes up the largest share) — was 46.1% for individuals with a prior infection alone, 55.1% for people who had a prior infection and also received two doses of the Pfizer/BioNTech vaccine (Comirnaty), 52.2% for those who received three vaccine doses but had no prior infection, and 77.3% for those with a prior infection and three vaccine doses.

Effectiveness against symptomatic BA.2 infection with two doses of Pfizer’s vaccine and no prior infection was essentially nil (-1.1%), with most individuals having received their second dose more than 8 months prior, but this group still saw substantial protection (76.8%) against severe, critical, or fatal cases of COVID-19.

Across the four other types of immunity, effectiveness against severe outcomes or worse from a BA.2 infection were as follows:

• Prior infection but not vaccinated: 73.4% (95% CI 0.2-92.9)
• Two doses plus prior infection: 97.8% (95% CI 82.6-99.7)
• Three doses but no prior infection: 98.2% (95% CI 91.9-99.6)
• Three doses plus prior infection: 100.0% (95% CI 82.6-100.0)

“Even though the five forms of immunity investigated showed large differences in protection against symptomatic infection that ranged from 0 to 80%, they all showed strong protection against COVID-19-related hospitalization and death,” wrote Abu-Raddad and co-authors. “This suggests that any form of previous immunity … is associated with strong and durable protection against COVID-19-related hospitalization and death.”

Similar results were observed when the researchers looked at protection against BA.1 infection or Moderna’s mRNA vaccine (Spikevax) rather than Pfizer’s. They also saw no evidence of a difference in disease severity between the two Omicron subvariants in their study population, which skewed younger.

An analysis of effectiveness based on the time since infection or vaccination “showed rapidly waning vaccine protection after the second and third doses but slowly waning protection from previous infection,” the group highlighted.

For example, protection against a new symptomatic Omicron infection (BA.1 or BA.2) following a past infection 4 to 6 months earlier was 65.7%, which declined slightly to 54.9% at 12 months or more.

With Pfizer’s vaccine, protection against a symptomatic Omicron infection started at 40.7% in the 14 days to 3 months following the second dose but essentially vanished at 6 months or more. A third vaccine dose, however, restored that earlier level of protection; most individuals who received a booster in the study did so within the past 45 days.

To evaluate the different types of immunity against the Omicron BA.1 and BA.2 variants, the researchers conducted a matched, test-negative, case-control study in Qatar from Dec. 23, 2021 to Feb. 21, 2022.

The five different groups — prior infection but no vaccination; two vaccine doses but no prior infection; two vaccine doses plus prior infection; three vaccine doses but no prior infection; and three vaccine doses plus prior infection — were compared with an unvaccinated group that had no evidence of prior infection. Classification of disease severity followed World Health Organization criteria.

Analysis for the Pfizer vaccine included 25,888 individuals who tested positive for COVID-19 by PCR, and these cases were matched by sex, age, week of testing, and nationality with an equal number of controls who had tested negative. Median participant age was 32 years, 54% were men, and Qatari (38%) and Indian (12%) were the predominant nationalities. For the Moderna vaccine analysis, 13,139 case patients were evaluated along with an equal number of controls. This group skewed a bit younger (median age 28-29 years; 56% men).

During the course of the large Omicron wave in Qatar, 315 random specimens were collected, of which Omicron was identified as the variant in 95% of the cases. This revealed a limitation to the data, in that Delta was still circulating during the study period at lower levels (4.8%). Of the cases identified as Omicron, 23.8% were BA.1 and 76.2% were BA.2.