Distribution of SARS-CoV-2 Variants in a Large Integrated Health Care System — California, March–July 2021

Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.^† Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4–7). This study used whole genome sequencing (WGS) data on SARS-CoV-2–positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4–July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2–positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4–May 19, 2021. During April 15–July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4–July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18–44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States.

KPSC facilities represent 15 large medical centers that provide care to approximately 4.6 million members across Southern California. As of 2021, KPSC performs molecular SARS-CoV-2 testing for all patients upon request, regardless of symptoms, and before hospital admission or medical procedures. During March 4–July 21, 2021, specimens were primarily collected via nasopharyngeal or oropharyngeal swab, but self-collection of saliva was also available. During this period, WGS was performed in accredited laboratories on all specimens collected by KPSC facilities that yielded a positive SARS-CoV-2 test result.^§,¶ The four most commonly identified SARS-CoV-2 variants were defined according to the CDC classification system as of September 2021.** All other identified variants were grouped together as ‘other’ variants. WGS data were linked with patient electronic medical records. The distributions (frequency and percentage) of variants were compared by week of specimen collection, vaccination status,^†† age, sex, race/ethnicity, and underlying medical conditions^§§ (8). Differences between groups were calculated using chi-square tests; statistical significance was defined as p<0.05.

Patients were followed up for 14 days from the date of SARS-CoV-2 specimen collection. COVID-19–related hospitalization was defined as hospital admission from 2 days before until 14 days after the SARS-CoV-2 positive test result. For patients hospitalized 0–2 days before the date of specimen collection, medical chart reviews were conducted to confirm that the hospitalization was related to COVID-19.^¶¶ For patients hospitalized during the 14 days after the specimen collection date, it was assumed that the hospitalization was related to the COVID-19 diagnosis. Cox proportional hazards regression analysis was used to obtain the adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) for the risk for COVID-19 hospitalization associated with the Delta variant (i.e., the predominant variant) relative to all other variants. Regression models were stratified by vaccination status, and were adjusted for age, sex, race/ethnicity, presence of underlying medical conditions, and study period. Data analyses were performed using SAS (version 9.4; SAS Institute). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.***

Among 6,798 sequenced SARS-CoV-2–positive specimens collected from KPSC patients during March 4–July 21, 2021, a total of 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons (Table) (Supplementary Figure 1, https://stacks.cdc.gov/view/cdc/110072). Approximately 45% of all positive SARS-CoV-2 specimens during March 4–July 21, 2021, failed sequencing; specimens most likely to fail sequencing were those collected from vaccinated persons, non-Hispanic Asians persons, older persons (those aged ≥65 years), and those with underlying medical conditions. Compared with unvaccinated persons, fully vaccinated persons were older and included a larger proportion of non-Hispanic Asian persons and persons with multiple underlying conditions. During March 4–May 19, 2021, the weekly percentage of infections attributed to the Alpha variant increased steadily from 20% to approximately 67%, after which it declined. During April 15–July 21, 2021, the weekly percentage attributed to the Delta variant increased from 0% to 95% of all sequenced specimens (Figure).

The absolute number of specimens that yielded a positive SARS-CoV-2 result was much lower among fully vaccinated persons (648) than among unvaccinated persons (5,994). In general, the weekly percentages of SARS-CoV-2 variants among fully vaccinated persons approximately mirrored those among unvaccinated persons (Supplementary Figure 2, https://stacks.cdc.gov/view/cdc/110120). However, overall, the percentage of fully vaccinated persons with infections attributed to the Delta variant was slightly higher (22%) than the percentage infected with other variants (4%–8%). There were slight differences in the distribution of selected variants by age group and race/ethnicity, but the distribution did not substantially differ between males and females, or between patients with and without multiple underlying medical conditions (Table). Compared with all infections, those from the Delta variant were slightly more common among non-Hispanic Black persons (16.4% versus 12.1%, respectively). Infections attributed to the Delta variant were also more common among younger persons, with the majority of infections identified among persons aged 18–44 years (55.3%). Twenty-five (3.9%) fully vaccinated patients and 393 (6.6%) unvaccinated patients were admitted to hospital within 2 days before to 14 days after the specimen collection date. Among unvaccinated persons, infection with the Delta variant compared with all other variants was associated with an increased adjusted risk of hospitalization (aHR = 1.81, 95% CI = 1.30–2.52).

Acknowledgments

Jennifer Charter, Lee Childs, Joy Gelfond, Radha Bathala, Yi Luo, Sarah Simmons, Gina S. Lee, Ayoola A. Ogun, Vivie Tang, Todd Choi, Raul Calderon, Kourtney Kottman, Ana Acevedo, Elmer Ayala, Jonathan Arguello, Kaiser Permanente Southern California; Helix OpCo, LLC; the patients of Kaiser Permanente Southern California.

Corresponding author: Deborah E. Malden, qdz7@cdc.gov.

¹Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California; ²Epidemic Intelligence Service, CDC; ³Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; ⁴Department of Health System Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California; ⁵Moderna, Inc., Cambridge, Massachusetts; ⁶Pfizer Inc., Collegeville, Pennsylvania.

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Abbreviations: FDA = Food and Drug Administration; IQR = interquartile range; N/A = not applicable.
* Vaccination status was defined as follows: fully vaccinated persons had completed all recommended doses of an FDA–authorized COVID-19 vaccine, including Pfizer-BioNTech, Moderna, and Janssen (Johnson & Johnson) ≥14 days before the positive SARS-CoV-2 test date; partially vaccinated persons had completed a single dose of Pfizer-BioNTech or Moderna COVID-19 vaccine ≥14 days before the positive SARS-CoV-2 test date; unvaccinated persons had no record of receiving a FDA-authorized COVID-19 vaccine ≥14 days before the positive SARS-CoV-2 test date.
^† Charlson Comorbidity Index is a weighted composite score based on 17 comorbidities.
^§ Chi-square test for heterogeneity.

FIGURE. Percentage of SARS-CoV-2 variants* identified among sequenced specimens, by unvaccinated (n = 5,994) and fully vaccinated (n = 648) status^† — California, March–July 2021

Abbreviation: FDA = Food and Drug Administration.

* Variants and their associated SARS-CoV-2 (Pango) lineages were defined according to the CDC classification system at the time of the report (https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html). The four most commonly identified variants were displayed separately, and all other identified lineages were grouped together as other variants.

^† Fully vaccinated persons had completed all recommended doses of an FDA-authorized COVID-19 vaccine, including Pfizer-BioNTech, Moderna, and Janssen (Johnson & Johnson) ≥14 days before the positive SARS-CoV-2 test date. Unvaccinated persons had no record of receiving an FDA-authorized COVID-19 vaccine ≥14 days before the positive SARS-CoV-2 test date. Partially vaccinated persons had completed a single dose of Pfizer-BioNTech or Moderna COVID-19 vaccine ≥14 days before the positive SARS-CoV-2 test date; these persons were not included in the current analysis because of sample size limitations.