Abstract
This study examines hospitalizations and deaths associated with the SARS-CoV-2 Omicron variant compared with matched patients infected with the Delta variant.
The World Health Organization designated Omicron as a variant of concern on November 26, 2021. Omicron has 37 mutations in the spike protein and has rapidly replaced Delta as the dominant variant globally, due to increased immune evasion.1 It is less clear how the severity of Omicron compares with that of Delta. Early data from South Africa suggest that Omicron may be less severe than prior lineages2; however, the low average age of infected individuals, extent of previous infection, and low vaccination rates affect generalizability to certain other countries. In Ontario, Canada, we examined hospitalizations and deaths associated with Omicron compared with matched patients infected with Delta.
Methods
We conducted a retrospective population-wide matched cohort study of patients infected with the Omicron and Delta variants, using Ontario-wide data sets: Public Health Case and Contact Management Solution, containing all SARS-CoV-2 infections diagnosed in Ontario, linked to the COVaxON database, containing all COVID-19 vaccination records. Cases were included if onset occurred between November 22, 2021 (first Omicron BA.1 sublineage case in Ontario), and December 24, 2021. The study period was prior to the January 2022 emergence of the Omicron BA.2 sublineage in Ontario. Case onset date was defined by symptom onset or, for asymptomatic cases, specimen collection. Cases were excluded if they were missing onset date, age, or sex or were hospital acquired.
A representative portion (stepping down from 50% to 10% on December 20, 2021) of case samples with cycle threshold of 30 or less were submitted for whole-genome sequencing (WGS). Between December 6 and 24, 2021, testing for S gene target failure (SGTF) was conducted for all cases in Ontario. Omicron cases were defined as cases identified by WGS, with SGTF and cycle threshold of 30 or less before December 13 (date of 50% Omicron prevalence),3 or all with SGTF after December 13. Delta cases were defined as cases detected by WGS, cases with amplification of the S gene, or all cases not identified as Omicron prior to December 3 (date of 5% Omicron prevalence).3 Omicron cases were matched 1:1 with Delta cases on sex, age in years, vaccination status, time since most recent vaccine dose, region, and onset date (±3 days).
Cox proportional hazards models accounting for clustering within matched sets were used to determine hazard ratios (HRs) for hospitalization, intensive care unit admissions, and deaths for Omicron compared with Delta cases, and 95% CIs, in R (version 4.1.0; R Foundation). Statistical significance was defined as a 95% CI that excluded 1. Stratified analyses were performed to evaluate differences in risk by sex, age group, and vaccination status. In a sensitivity analysis, potential incidental cases (first positive specimen collection on the day of or the day prior to hospitalization) were excluded. The Public Health Ontario Ethics Review Board determined that ethics committee approval or informed consent was not required because deidentified population data were used.
Results
We identified 37 296 Omicron cases that met eligibility criteria, of which 9087 (24.4%) were matched 1:1 with Delta cases (Table 1). The median follow-up time was 24 days (IQR, 21.0-28.0). There were 53 hospitalizations (0.6%) and 3 deaths (0.03%) among matched Omicron cases compared with 129 hospitalizations (1.4%) and 26 deaths (0.3%) among matched Delta cases. The HR for hospitalization or death among Omicron cases compared with Delta cases was 0.41 (95% CI, 0.30-0.55; 0.33 [95% CI, 0.19-0.56] in sensitivity analysis), while the HR for intensive care unit admission or death was 0.19 (95% CI, 0.09-0.39), and the HR for death was 0.12 (95% CI, 0.04-0.37). Stratified estimates of Omicron severity by age, sex, and vaccination status all indicated reduced Omicron severity (Table 2).
Table 1. Demographic Characteristics, Vaccination Status, and Outcomes Among SARS-CoV-2 Delta and Omicron Variant Cases.
| No. (%) | ||||
|---|---|---|---|---|
| Full cohort | Matched cohort | |||
| Delta (n = 24 432) | Omicron (n = 37 296) | Delta (n = 9087) | Omicron (n = 9087) | |
| Age, median (IQR), y | 33.0 (13.0-49.0) | 30.0 (21.0-44.0) | 32.0 (16.0-46.0) | 32.0 (17.0-46.0) |
| Sex | ||||
| Female | 12 038 (49.3) | 18 682 (50.1) | 4571 (50.3) | 4571 (50.3) |
| Male | 12 331 (50.5) | 18 577 (49.8) | 4511 (49.6) | 4511 (49.6) |
| Other | 63 (0.3) | 37 (0.1) | 5 (0.1) | 5 (0.1) |
| Vaccination status (doses and time since last dose) | ||||
| 0 doses | 10 900 (44.6) | 4784 (12.8) | 2823 (31.1) | 2823 (31.1) |
| 1 dose | ||||
| >14 d-<3 mo | 1096 (4.5) | 1617 (4.3) | 551 (6.1) | 551 (6.1) |
| 3-<6 mo | 159 (0.7) | 110 (0.3) | 29 (0.3) | 29 (0.3) |
| ≥6 mo | 154 (0.6) | 132 (0.4) | 18 (0.2) | 18 (0.2) |
| 2 doses | ||||
| >7d-<3 mo | 509 (2.1) | 865 (2.3) | 162 (1.8) | 162 (1.8) |
| 3-<6 mo | 3392 (13.9) | 8714 (23.4) | 1724 (19.0) | 1724 (19.0) |
| ≥6 mo | 6183 (25.3) | 17 102 (45.9) | 3146 (34.6) | 3146 (34.6) |
| 3 doses | ||||
| >7d-<3 mo | 1975 (8.1) | 3841 (10.3) | 622 (6.8) | 622 (6.8) |
| 3-<6 mo | 64 (0.3) | 130 (0.3) | 12 (0.1) | 12 (0.1) |
| ≥6 mo | 0 | 1 (0.003) | 0 | 0 |
| Outcomes | ||||
| Hospitalization/death | 689 (2.8) | 115 (0.3) | 129 (1.4) | 53 (0.6) |
| ICU admission/death | 248 (1.0) | 21 (0.1) | 42 (0.5) | 8 (0.1) |
| Deaths | 133 (0.5) | 12 (0.03) | 26 (0.3) | 3 (0.03) |
Abbreviation: ICU, intensive care unit.
Table 2. Risk of Hospitalization, ICU Admission, or Death Among SARS-CoV-2 Omicron Variant Cases Relative to Delta, Ontario, Canada.
| Matched pairs, No. (%) | HR (95% CI)a | |||
|---|---|---|---|---|
| Hospitalization or death | ICU admission or death | Hospitalization or death, sensitivity analysisb | ||
| Total | 9087 (100.0) | 0.41 (0.30-0.55) | 0.19 (0.09-0.39) | 0.33 (0.19-0.56) |
| Stratified analyses | ||||
| Sex | ||||
| Female | 4571 (50.3) | 0.47 (0.31-0.73) | 0.23 (0.07-0.74) | 0.61 (0.29-1.29) |
| Male | 4511 (49.6) | 0.36 (0.24-0.54) | 0.17 (0.07-0.43) | 0.18 (0.08-0.41) |
| Age, y | ||||
| <60 | 8215 (90.4) | 0.42 (0.25-0.70) | 0.10 (0.01-0.78) | 0.47 (0.21-1.05) |
| ≥60 | 872 (9.6) | 0.39 (0.28-0.57) | 0.21 (0.10-0.46) | 0.24 (0.11-0.51) |
| Vaccine doses | ||||
| 0 doses | 2823 (31.1) | 0.41 (0.26-0.64) | 0.31 (0.13-0.76) | 0.21 (0.07-0.61) |
| 2 doses | 5032 (55.4) | 0.44 (0.29-0.65) | 0.09 (0.02-0.38) | 0.40 (0.20-0.80) |
Abbreviations: HR, hazard ratio; ICU, intensive care unit.
All analyses based on proportional hazards models and presented as HRs. HRs of 1 indicate equal risk for Omicron relative to Delta, of less than 1 indicate reduced severity of Omicron, and of more than 1 indicate increased severity of Omicron.
Sensitivity analysis excludes Delta or Omicron cases with potential incidental SARS-CoV-2 findings (first positive specimen collection on the day of or the day prior to hospitalization).
Discussion
In this matched study of more than 9000 Omicron cases in Ontario, the risk of hospitalization or death was lower for Omicron cases compared with Delta cases. The results align with findings from South Africa, Scotland, and England, all of which have demonstrated substantial decreases in risk associated with Omicron.4,5,6
This study has some limitations, in particular the short follow-up duration, potential misclassification due to incidental findings from hospital admission screening, and incomplete public health follow-up as incidence increased. While severity may be reduced among Omicron cases, the absolute number of hospitalizations and the effects on health care systems are likely to be significant due to the elevated incidence of Omicron.
Section Editors: Jody W. Zylke, MD, Deputy Editor; Kristin Walter, MD, Associate Editor.
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