Effectiveness of mRNA-1273 against infection and COVID-19 hospitalization with SARS-CoV-2 Omicron subvariants: BA.1, BA.2, BA.2.12.1, BA.4, and BA.5

Abstract

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against Omicron BA.4/BA.5 compared with earlier Omicron subvariants. We conducted a test-negative case-control study evaluating mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron subvariants. The study included 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection was high and waned slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection was initially moderate to high (61.0%-90.6% 14-30 days post third dose) and waned rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranged between 64.3%-75.7%, and was low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 was 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 was 88.5%. Evaluation of the updated bivalent booster is warranted.

Effectiveness of Monovalent mRNA Vaccines Against COVID-19–Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States — IVY Network, 18 States, December 26, 2021–August 31, 2022

“…In contrast, a cohort study in Portugal found reduced protection against severe outcomes during BA.5 predominance (4). This was similar to U.S. findings, which indicated that 3-dose VE against hospitalization was lower during the BA.4/BA.5 period compared with the BA.1 period, although these VE estimates did not account for time after the last vaccine dose (5). Third, infection-induced immunity in the population substantially increased during and after the BA.1 period.…”

“…Second, increased immune evasion of BA.4/BA.5 lineages has been shown in neutralization assessments and may contribute to lower VE (10). However, the extent to which reduced neutralization in vitro correlates with reduced protection against severe disease is unknown; available studies have shown mixed results (2)(3)(4)(5). A study from South Africa showed no difference in VE of 3 monovalent mRNA vaccine doses against hospitalization during the BA.4/BA.5 period compared with the BA.1/BA.2 period at the same intervals from vaccination, which was corroborated by findings from the United Kingdom showing similar VE against BA.2-or BA.4/BA.5-related hospitalizations (2,3).…”

“…BA.1 has since been replaced by emerging lineages BA.2 (including BA.2.12.1) in March 2022, followed by BA.4 and BA.5, which have accounted for a majority of SARS-CoV-2 infections since late June 2022 (1). Data on the effectiveness of monovalent mRNA COVID-19 vaccines against BA.4/BA.5associated hospitalizations are limited, and their interpretation is complicated by waning of vaccine-induced immunity (2)(3)(4)(5). Further, infections with earlier Omicron lineages, including BA.1 and BA.2, reduce vaccine effectiveness (VE) estimates because certain persons in the referent unvaccinated group have protection from infection-induced immunity.…”

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome

“…Reassuringly, however, our findings are consistent with previous evidence that vaccination remains protective against severe disease associated with the BA.4/BA.5 lineages, at levels comparable to those reported for the BA.2 lineage. 5,[19][20][21] Within our large sample of 49,976 BA.2 cases and 59,556 BA.4/BA.5 cases, vaccination was not associated with statistically meaningful differences in estimates of protection against progression from an initial outpatient diagnosis to subsequent illness requiring ED presentation or either hospital or ICU admission. As our study is limited to infected cases who received clinical molecular testing, it is important to note our findings do not measure the effectiveness of prior infection or vaccination against infection with either lineage BA.4/BA.5 or BA.2 lineages.…”

Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes

“…23 A study among Kaiser Permanente members found that VE of third and fourth doses against BA.4/BA.5-related hospitalizations was lower compared to BA.1/BA.2-related hospitalizations, whereas another study among individuals admitted to IVY Network hospitals saw this difference for a third dose but not for 2 or 4 doses. 24,25 The IVY Network study reported 3-dose VE of 79% (95%CI, 74-84%) and 60% (95%CI, 12-81%), respectively, during the BA.1/BA.2-predominant versus BA.4/BA.5-predominant periods 7-120 days after vaccination. 25 Potential explanations for lower VE during the period of BA.4/BA.5-predominance compared to BA.1/BA.2-predominance include longer intervals between booster dose receipt and outcomes, increased incidence of undocumented infections, and increased BA.4/BA.5 immune evasion.…”