In a recent study published on the medRxiv* preprint server, researchers compared the clinical outcomes of cases of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA. 2 and Omicron BA.4 Variants /BA.5 based on Kaiser Permanente Southern California (KPSC) health records between April 29 and July 2, 2022.
Study: Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome. Image credit: Sutthituch/Shutterstock
background
The incidence of BA.4/BA.5 variant infections among individuals with pre-existing immunity to SARS-CoV-2 from previous infections or vaccinations has raised health concerns related to Omicron BA.4 evasive immunity /BA.5. The clinical implications of the emergence of BA.4 and BA.5 have been unclear, with varying counts of BA.4/BA.5 infections associated with hospitalizations and deaths.
About the study
In the present longitudinal study, investigators assessed the differential severity of Omicron BA.4/BA.5 infections relative to Omicron BA.2 infections.
The number of COVID-19 vaccines administered was identified by linkage to California immunization registry data. Nearly 19% (4.7 million members as of 2022) of the Southern California population receives KPSC care through prepaid, federally sponsored, or employer-provided insurance plans. Outpatients with COVID-19 were recruited with a home follow-up program based on standard criteria for inpatient admissions and ED referrals.
In-network delivery data including diagnosis, clinic notes, vaccines, prescriptions and lab reports are captured by KPSC in real-time through the patient’s electronic medical records (EHR) and out-of-network care is captured through reimbursements for insurance claims. . The team excluded individuals identified as SARS-CoV-2-positive in hospital settings or those identified as SARS-CoV-2-positive ≤90 days before the start of the study. In addition, individuals were excluded if they withdrew before the study end date or after 60 days from the test date.
Study outcomes/aims were: (i) emergency department (ED) presentation; (ii) Presentation of ED with symptoms ≤ 2 weeks days after onset of symptoms; (iii) inpatient admissions; (iv) inpatient admissions with symptoms ≤2 weeks after symptom onset; (v) intensive care unit (ICU) admission; (vi) mechanical ventilation needs; and (vii) dead.
For outcomes such as ED presentations, symptomatic ED presentations, hospitalizations, and symptomatic hospitalizations, follow-up assessments were performed ≤ 30 days after testing positive for SARS-CoV-2 in outpatient settings. For outcomes such as ICU admissions, mechanical ventilation requirements, and deaths, participants were followed for ≤ 30 days from their reports of positive ambulatory tests for SARS-CoV-2. In addition, sensitivity analyzes were performed by repeating the survival analyzes of ED presentations and symptomatic ED presentations for cases with a history of COVID-19.
Molecular tests for the detection of SARS-CoV-2 included real-time polymerase chain reaction (rt-PCR) analyzes and probes targeting the SARS-CoV-2 nucleocapsid (N), reading frames open 1 a/b (ORF1a/b) and spike (S) genes. S gene target failure (SGTF) analysis was used to distinguish between BA.2 and BA.4/BA.5 variants. Logistic regression models and Cox proportional models (survival analysis) adjusted for included covariates were used for analysis. Adjusted odds ratios (OR), adjusted hazard ratios (aHR) and 30-day crude incidence rates per 1000 cases were calculated.
results
A total of 65,694 outpatient cases of COVID-19 (out of a total of 81,880 cases) were analyzed, of which 26% (n=16,753) were BA.4/BA.5 infections and 75% (n =-48.941) by Omicron BA. .2 infections, respectively. Of the cases randomly selected by KPSC for genomic sequencing in 2022, 99.6% (n=243) and 99% (n=406) of Omicron BA.4 and Omicron BA.5 cases showed SGTF and, in instead, SGTF was not observed in 98% (n=2,000) of Omicron BA.2 cases.
Among Omicron BA.4/BA.5 cases, 17%, 2.5%, 24%, 49%, and 7.5% of individuals received zero, one, two, three, and four doses of vaccine against COVID-19, respectively, before their diagnoses. The corresponding vaccination rates among individuals with Omicron BA.2 cases were 18%, 2.5%, 25%, 49%, and 5.9%, respectively. The aORs of receiving three and four doses of COVID-19 vaccines were 1.1-fold and 1.3-fold higher for Omicron BA.4/BA.5 infections compared with Omicron BA infections. 2.
Previous history of COVID-19 ≥90 days prior to positive SARS-CoV-2 test results was documented for 4.5% and 2.9% of Omicron BA.4/BA.5 and Omicron cases BA.2, respectively. ORs for prior documentation of COVID-19 were 1.6 times higher for Omicron BA.4/BA.5 cases than for Omicron BA.2 cases. For 4,349 cases of BA.4/BA.5 infections, 30-day crude incidence rates for symptomatic ED presentations, all ED presentations, symptomatic inpatient admissions, all inpatient admissions and ICU admissions were 25, 26, 2.3, 3.0 and 0.2. , respectively, without the need for mechanical ventilation and deaths.
For 32,592 cases of Omicron BA.2 infection, the corresponding rates of symptomatic ED presentations, all ED presentations, symptomatic inpatient admissions, all inpatient admissions, mechanical ventilation requirements, ICU admissions, and deaths were 24, 26, 2.6, 3.0, 0.3, 0.3. , and 0.2, respectively. The AHRs for cases of Omicron BA.4/BA.5 infection compared with cases of Omicron BA.2 infection were 1.1, 1.1, 1.0, 1.1, and 0, 9 for symptomatic ED presentations, all ED presentations, symptomatic hospitalizations, all inpatient and ICU admissions. admissions, respectively.
No cases of Omicron BA.4/BA.5 infection required mechanical ventilation or died, and therefore AHRs could not be calculated for both outcomes. Omicron BA.4/BA.5 cases diagnosed in ambulatory settings had 55% greater odds of a prior history of COVID-19 compared with contemporary ambulatory-diagnosed Omicron BA.2 cases, and modestly higher odds older than receiving ≥3 doses of COVID-19. vaccines
Overall, the study’s findings showed that despite the high risks of breakthrough Omicron BA.4 and BA.5 infections among previously infected or vaccinated individuals, the reduced severity of Omicron BA.2 infections was persistent with Omicron BA.4/BA.5 infections.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.