In a recent study posted to the medRxiv* preprint server, researchers compared the vaccine effectiveness (VE) against infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) Omicron BA.1 and BA.2 sublineages in Sweden.
Studies have reported that the Omicron BA.2 sublineage is more transmissible than BA.1, with lower protection conferred by vaccines against BA.2-associated hospitalizations and deaths. However, some studies have reported equivalent protection for both sublineages. Therefore, robust evidence on the comparative VE against BA.1 and BA.2 sublineages is lacking.
About the study
In the present cohort study, researchers compared VE against severe coronavirus disease 2019 (COVID-19) caused by BA.1 and BA.2 sublineages of the Omicron VOC between December 27, 2021, and March 15, 2022, among Scania County residents of southern Sweden. The individuals were longitudinally followed up for positive COVID-19 reports, and hospitalizations, and were assessed for COVID-19 severity.
Data for all residents of Scania were obtained from routine sample sequencing of COVID-19 cases for comparative VE assessment during three periods: (i) BA.1 predominance (60%) in week 52, 2021 and week 1, 2022, (ii) transitional period during week 2 and 3, 2022 (BA.1 47%, BA.2 49%), and (iii) Omicron BA.2 predominance (82%), weeks 4 to 11 of 2022.
Data on all the residents were obtained from regional and national registries by linking the personal identification number of the residents. Updates were obtained weekly on the vaccination type, date, and doses provided by the national vaccination register.
Data on severe COVID-19 patients were provided by the SMINet, an electronic system of Sweden’s public health agency. In addition, regional registers of health were used as sources of complementary data to rapidly provide COVID-19 tests data and to evaluate the impact of comorbidities on COVID-19 outcomes. The comorbid conditions assessed included diabetes, obesity, and disorders of renal, hepatic, pulmonary, neurological systems, cancer, immunosuppressive conditions, and genetic diseases such as Down’s Syndrome, thalassemia, and sickle cell anemia.
Severe COVID-19 cases were those with a minimum of one-day hospitalization five days before and up to two weeks after positive COVID-19 reports with oxygen supplementation requirements of ≥ 5 L/minute or intensive care unit (ICU) admissions.
The continuous density case-control sampling technique was used for matching the case and controls for age and sex and making data adjustments for differences in comorbidities and COVID-19 history. Logistic regression modeling and 95% confidence intervals (CI) were used to compare VE for severe SARS-CoV-2 infections.
For every severe COVID-19 case, 10 individuals with SARS-CoV-2-negative reports obtained 90 days before or in the same timeframe as that of SARS-CoV-2-positive cases were randomly chosen as controls. Only vaccinations administered a week before the date of COVID-19 diagnosis were selected for the analyses.
Over 590 severe COVID-19 cases were detected during the follow-up assessments, that corresponded to weekly 65 BA.1 predominant cases, 78 BA.1 to BA.2 transition cases, and 56 BA.2 cases. Although most (83%) of the study participants were vaccinated, only 57% booster vaccine uptake was observed. Most (77%) of the study participants were vaccinated with the BNT16b2 messenger ribonucleic acid (mRNA) vaccine. The severe BA.2 cases were more prevalent in the elderly with a more uniform prevalence among both the sexes compared to BA.1 cases.
Before follow-up, VE against severe SARS-CoV-2 infections was high (mean VE 89%) between March and November 2021) and was stable during BA.1 predominance in December 2021. However, after two doses, VE declined remarkably from 90% (95% CI 78% to 95%) during BA.1 predominance to 54% (95% CI 13% to 75%) during BA.2 predominance. In addition, vaccine protection from prior COVID-19 history was also lower after the transition to BA.2. This decline in VE was consistent across all ages, comorbidities, and sexes. In contrast, among participants who received three vaccine doses, the VE remained stable after the transition from BA.1 to BA.2.
To summarize, the study findings highlighted the importance of booster vaccination to mitigate COVID-19 and that the immune-evasive Omicron BA.2 sublineage was more likely to cause severe SARS-CoV-2 infections compared to the BA.1 sublineage. However, further studies for continued monitoring of VE against BA.2 are required.
Data on the causative viral variants for every case for every period were lacking. Thus, the true changes in VE during the transition from BA.1 to BA.2 could have been underestimated. In addition, the protection from the history of Omicron infections could not be evaluated since the period of follow-up with Omicron predominance is short.
Further, since routine testing is not recommended any longer, VE against infections could not be thoroughly investigated. Additionally, the study results had high statistical uncertainty, indicated by wide CIs among the subgroups.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.