This cohort study assesses the severity of clinical outcomes in persons infected with the SARS-CoV-2 Delta variant vs the Beta variant in Qatar.
Key Points
Question
Do patients infected with the SARS-CoV-2 Delta variant experience more severe disease outcomes compared with those infected with the Beta variant?
Findings
In this cohort study of 1427 persons infected with the Delta variant and 5353 persons infected with the Beta variant in Qatar, among 451 propensity score–matched pairs identified, persons infected with the Delta variant were more likely to be hospitalized (27.3% vs 20.0%) or to experience more severe disease outcomes. Infection with the Delta variant was independently associated with higher odds of experiencing any adverse outcome, and vaccination was associated with significantly reduced odds of severe disease outcomes.
Meaning
In this cohort study, infection with the Delta variant was more severe than infection with the Beta variant in persons in Qatar, although vaccination was highly protective against severe outcomes for both variants.
Abstract
Importance
The Delta variant is now the predominant circulating SARS-CoV-2 strain worldwide. Severity of illness in persons infected with the SARS-CoV-2 Delta variant compared with the Beta variant is not known.
Objective
To directly compare clinical outcomes in persons infected with the SARS-CoV-2 Delta variant vs those infected with the Beta variant in Qatar.
Design, Setting, and Participants
This retrospective cohort study used data from the national COVID-19 database in Qatar, which includes information on all individuals who were ever tested for SARS-CoV-2 using a reverse transcriptase–polymerase chain reaction test and all individuals who received any SARS-CoV-2 vaccine in Qatar. Among persons with confirmed SARS-CoV-2 infection between March 22 and July 7, 2021, those infected with the Delta variant were identified and were propensity score matched with control individuals infected with the Beta variant. The variants were ascertained by variant genotyping of the positive samples.
Exposures
SARS-CoV-2 infection with the Delta or Beta variant.
Main Outcomes and Measures
The main outcomes were admission to the hospital, admission to the intensive care unit, use of supplemental oxygen, use of high-flow oxygen, receipt of mechanical ventilation, or death among those infected with the Delta or Beta variant overall and stratified by vaccination status.
Results
Among 1427 persons infected with the Delta variant (252 [55.9%] male; median age, 34 years [IQR, 17-43 years]) and 5353 persons infected with the Beta variant (233 [51.7%] male; median age, 34 years [IQR, 17-45 years]), 451 propensity score–matched pairs were identified. Persons infected with the Delta variant were more likely to be hospitalized (27.3% [95% CI, 23.2%-31.6%] vs 20.0% [95% CI, 16.4-24.0]; P = .01) or to have mild-moderate or severe-critical disease outcomes (27.9% [95% CI, 23.8%-32.3%] vs 20.2% [95% CI, 16.6%-24.2%]; P = .01) compared with persons infected with the Beta variant. Infection with the Delta variant was independently associated with higher odds of experiencing any adverse outcome (adjusted odds ratio [aOR], 2.53; 95% CI, 1.72-3.72). Compared with being unvaccinated, being vaccinated with a second dose more than 3 months before infection was associated with lower odds of any adverse outcome among persons infected with the Delta variant (aOR, 0.11; 95% CI, 0.04-0.26) and among those infected with the Beta variant (aOR, 0.22; 95% CI, 0.05-0.98). Protection was similar among those who received a second vaccine dose less than 3 months before infection, but having received only a single dose was not associated with a lower odds of any severe outcome among those infected with the Delta variant (aOR, 1.12; 95% CI, 0.41-3.06) or those infected with the Beta variant (aOR, 0.74; 95% CI, 0.20-2.72).
Conclusions and Relevance
In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.
Introduction
The COVID-19 pandemic has rapidly evolved over time, with new viral strains appearing at regular and frequent intervals. The new strains, which are associated with substantial changes in the behavior of the virus and/or its effect on the host have been termed variants of concern (VOCs) and labeled with the Greek alphabet sequentially. A more recent entrant and now the predominant VOC worldwide is the Delta variant. Originally identified in India, the Delta variant has spread rapidly in the US, with more than 90% of the infections in the US now being caused by the Delta variant.1,2 It has been suggested that transmission by asymptomatic infected persons has led to a large increase in COVID-19 cases due to the Delta variant.3 However, there is evidence that the Delta variant is more infectious and associated with higher viral load and ability to escape in vivo neutralization.4,5,6 Infection with the Delta variant has also been recently associated with more severe disease and poorer clinical outcomes compared with the wild-type and Alpha variants.7,8 The risk is significantly higher in unvaccinated persons.7,8 Current vaccines have been found to be highly effective against the Delta variant, particularly in preventing severe and critical disease, although their effectiveness is somewhat lower compared with their effectiveness against the previous variants.9,10,11,12,13 To our knowledge, no large-scale study has directly compared outcomes in persons infected with the Delta variant vs the Beta variant. We undertook this study to directly compare the clinical outcomes in persons infected with the Delta variant vs those infected with the Beta variant in a national setting.
Methods
Study Setting
This cohort study was conducted in Qatar, which has one of the highest rates of testing and vaccination of the eligible population for SARS-CoV-2 in the world.14 Since the identification of the first patient with SARS-CoV-2 infection on February 27, 2020, Qatar has experienced 4 distinct waves attributed to the wild-type, Alpha, and Beta variants, with recent incidence being dominated by the Delta variant.15,16,17,18 Starting early in the pandemic, Qatar also instituted an aggressive testing policy, which included testing of all persons with compatible symptoms, contacts of persons with confirmed cases, returning travelers, and persons in frontline, high-risk professions (eg, health care workers, school staff, and salon and spa workers). Multiple general screening campaigns were also carried out, targeting persons in high-incidence areas and large convenience samples. Reverse transcriptase–quantitative polymerase chain reaction (RT-qPCR) was used to test for SARS-CoV-2 in nasopharyngeal swab samples at a single national laboratory at Hamad Medical Corporation, which is accredited by the College of American Pathologists and the Joint Commission International. Surveillance for SARS-CoV-2 variants in Qatar was based on viral genome sequencing and multiplex, real-time RT-qPCR variant genotyping19 of random positive clinical samples17,18,20,21,22 and was complemented by deep sequencing of wastewater samples.22 The study was approved by the institutional review board at Hamad Medical Corporation. A waiver of informed consent was granted for the study owing to the use of retrospective data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Study Participants
All persons in Qatar with a nasopharyngeal swab sample positive for SARS-CoV-2 between March 22 and July 7, 2021, were eligible for inclusion in the study. SARS-CoV-2 testing and results were retrieved from the national COVID-19 database, which includes every result of PCR tests performed in Qatar since the beginning of the pandemic.20,21,23 Among persons who tested positive between those dates, we identified those with variant genotyping performed on their positive sample. For each person with a confirmed Delta variant infection, we identified a propensity score–matched control individual with a Beta variant infection. Propensity score matching was done based on demographic and clinical variables and vaccination status. Body mass index data were missing for 3690 cases and thus were excluded from the data frame. A propensity score was estimated based on age, sex, nationality, vaccination status at time of infection, and the following comorbidities: asthma, cancer, chronic kidney disease, chronic liver disease, chronic lung disease, coronary artery disease, diabetes, hypertension, and stroke. We performed 1:1 matching using the nearest neighbor matching with a caliper of 0.2 SD.
Definitions
The primary outcome of interest was a composite of any SARS-CoV-2–related adverse disease outcomes in persons infected with the Delta variant and those infected with the Beta variant. These outcomes included admission to the hospital, care in the intensive care unit, use of supplemental oxygen, use of high-flow oxygen, receipt of mechanical ventilation, and death. Secondary outcomes included mild-moderate disease and severe-critical disease in persons infected with the Delta variant and those infected with the Beta variant. Disease severity was based on modified World Health Organization criteria, which have been used in previous publications.23,24 Mild-moderate illness was defined as admission to a non–intensive care unit or use of supplemental oxygen. Severe-critical illness was defined as care in an intensive care unit, need for high-flow oxygen or mechanical ventilation, or death. Information at admission to the hospital and data regarding care in the intensive care unit, use of supplemental oxygen, use of high-flow oxygen, receipt of mechanical ventilation, and death were extracted from each person’s electronic medical record by trained personnel using structured individual medical record reviews. All outcomes were recorded for the duration of the index hospital stay related to the COVID-19 diagnosis or within 28 days of the index positive test result, whichever was longer. Comorbidities were identified based on associated diagnostic codes in the electronic medical records, as used in previous publications.25,26,27 SARS-CoV-2 infection was confirmed from the national COVID-19 database, which includes every test performed in Qatar since the beginning of the pandemic.20,21,23 Vaccination status, type of vaccine, and date(s) of administration were also confirmed from the national COVID-19 database, which contains a record of every SARS-CoV-2 vaccine administered in Qatar.20,21
Laboratory Methods and Classification by Variant Type
Nasopharyngeal and/or oropharyngeal swab samples were collected for PCR testing and placed in universal transport medium. Aliquots of Universal Transport Medium were extracted on a QIAsymphony platform (Qiagen) and tested with real-time RT-qPCR using TaqPath COVID-19 Combo Kits (Thermo Fisher Scientific) on an ABI 7500 FAST (Thermo Fisher). They were tested directly on the Cepheid GeneXpert system using the Xpert Xpress SARS-CoV-2 (Cepheid) or loaded directly into a Roche cobas 6800 system and assayed with a cobas SARS-CoV-2 Test (Roche). The first assay targets the viral S, N, and ORF1ab gene regions. The second targets the viral N and E-gene regions, and the third targets the ORF1ab and E-gene regions. All PCR testing was conducted at the Hamad Medical Corporation central laboratory following standardized protocols.
Surveillance for SARS-CoV-2 variants in Qatar is based on viral genome sequencing and multiplex, real-time RT-qPCR variant screening19 of random positive clinical samples17,18,20,21,22 and is complemented by deep sequencing of wastewater samples.22 The ascertainment of the Beta and Delta variants in this study was based on the results of the weekly RT-qPCR genotyping of the positive clinical samples.18,22 Between March 22 and August 3, 2021, RT-qPCR genotyping identified 5480 (45.8%) B.1.351-like cases, 3233 (27.0%) B.1.1.7-like cases, 3223 (26.9%) other variant cases, and 41 (0.3%) B.1.375-like and B.1.258-like cases in 11 977 randomly collected SARS-CoV-2–positive specimens.18,22
The accuracy of the RT-qPCR genotyping was verified against either Sanger sequencing of the receptor-binding domain of SARS-CoV-2 surface glycoprotein (S) gene or by viral whole-genome sequencing on a Nanopore GridION sequencing device. From 236 random samples (27 B.1.1.7-like, 186 B.1.351/P.1-like, and 23 other variants), the PCR genotyping results for B.1.1.7-like, B.1.351/P.1-like, and other variants were in 88.8% (23 of 27), 99.5% (185 of 186), and 100% (23 of 23) agreement, respectively, with the SARS-CoV-2 lineages assigned by sequencing.18,22 Within the other variant category, Sanger sequencing and/or Illumina sequencing of the receptor-binding domain of SARS-CoV-2 spike gene on 457 random samples confirmed that 433 (94.7%) were B.1.617.2 cases, 8 (1.8%) were B.1.617.1 cases, 3 (0.7%) were B.1 cases, 1 (0.2%) was a B.1.351/P.1 case, 1 (0.2%) was a P.1 case, and 1 (0.2%) was a B.1.617.3 case, with 10 (1.1%) samples failing lineage assignment.18,22 Accordingly, a Delta variant case was proxied as any other case identified through the RT-qPCR–based variant screening. All variant genotyping was conducted at the Sidra Medicine Laboratory following standardized protocols.
Statistical Analyses
Baseline characteristics of persons infected with the Delta variant were compared with those of persons infected with the Beta variant using the χ2 or Mann-Whitney test, as appropriate. Proportions of persons with each outcome among those infected with the Delta and Beta variants were calculated and compared overall and stratified by vaccination status; 95% CIs were calculated to express the spread. Multivariable logistic regression was used to calculate the adjusted odds ratios (aORs) and 95% CIs for factors associated with primary and secondary outcomes. Significance was defined at 2-sided P < .05. All analyses were done using SPSS, version 27.0 (IBM).
Results
We identified 1427 persons infected with the Delta variant and 5353 persons infected with the Beta variant between March 22 and July 7, 2021. Among those, we identified 451 propensity score–matched pairs infected with the Delta and Beta variants. The median age was 34 years (IQR, 17-43 years) among those infected with the Delta variant and 34 years (IQR, 17-45 years) among those infected with the Beta variant; 252 individuals infected with the Delta variant (55.9%) and 233 infected with the Beta variant (51.7%) were male, and 171 (37.9%) and 124 (27.5%), respectively, were Qatari nationals (Table 1). Among those with Delta variant infection, 53.7% (95% CI, 48.9%-58.3%) had no comorbidity, 18.9% (95% CI, 15.3%-22.8%) had 1 comorbidity, and 27.5% (95% CI, 23.4%-31.9%) had more than 1 comorbidity. Among those with Beta variant infection, 55.0% (95% CI, 50.3%-60.0%) had no comorbidity, 18.8% (95% CI, 15.3%-22.8%) had 1 comorbidity, and 26.2% (95% CI, 22.2%-30.5%) had more than 1 comorbidity. Distribution of individual comorbidities is provided in Table 1.
Table 1. Baseline Characteristics of Propensity Score–Matched Persons Infected With the Delta and Beta Variants.
| Characteristic | Persons, No. (%) [95% CI] | P value | |
|---|---|---|---|
| Delta variant infection (n = 451) | Beta variant infection (n = 451) | ||
| Age, y | |||
| Median (IQR) | 34 (17-43) | 34 (17-45) | .59a |
| 0-19 | 125 (27.7) [23.6-32.1] | 121 (26.8) [22.8-31.2] | .99b |
| 20-39 | 173 (38.4) [33.9-43.0] | 174 (38.6) [34.1-43.3] | |
| 40-59 | 125 (27.7) [23.6-32.1] | 127 (28.2) [24.1-32.6] | |
| ≥60 | 28 (6.2) [4.2-8.9] | 29 (6.4) [4.4-9.1] | |
| Sex | |||
| Female | 199 (44.1) [39.5-48.8] | 218 (48.3) [43.6-53.1] | .20b |
| Male | 252 (55.9) [51.2-60.5] | 233 (51.7) [46.9-56.4] | |
| Nationality | |||
| Qatari | 171 (37.9) [33.4-42.6] | 124 (27.5) [23.4-31.9] | <.001b |
| Indian subcontinent and Sudanc | 154 (34.2) [29.8-38.7] | 156 (34.6) [30.2-39.2] | |
| Otherd | 126 (27.9) [23.8-32.3] | 171 (37.9) [33.4-42.6] | |
| Body mass indexe | |||
| Median (IQR) | 25.8 (21.2-30.3) | 26.6 (21.6-30.5) | .25a |
| Underweight | 69 (15.3) [12.1-19.0] | 73 (22.4) [18.6-26.5] | .18b |
| Normal weight | 139; 30.8 (26.6-35.3) | 110 (26.4) [22.4-30.7] | |
| Overweight | 126 (27.9) [23.8-32.3] | 144 (31.7) [27.4-36.2] | |
| Obesity | 117 (25.9) [22.0-30.3] | 124 (19.5) [16.0-23.5] | |
| Comorbidities | |||
| Asthma | 163 (36.1) [31.7-40.8] | 132 (29.3) [25.1-33.7] | .03b |
| Cancer | 4 (0.9) [0.2-2.3] | 8 (1.8) [0.8-3.5] | .24b |
| Chronic kidney disease | 8 (1.8) [0.8-3.5] | 7 (1.6) [0.6-3.2] | .79b |
| Chronic liver disease | 2 (0.4) [0.1-1.6] | 3 (0.7) [0.1-1.9] | >.99f |
| Chronic obstructive pulmonary disease | 78 (17.3) [13.9-21.1] | 62 (13.7) [10.7-17.3] | .14b |
| Coronary artery disease | 11 (2.4) [1.2-4.3] | 17 (3.8) [2.2-6.0] | .25b |
| Diabetes | 62 (13.7) [10.7-17.3] | 79 (17.5) [14.1-21.4] | .12b |
| Hypertension | 54 (12.0) [9.1-15.3] | 77 (17.1) [13.7-20.9] | .03b |
| Stroke | 2 (0.4) [0.1-1.6] | 4 (0.9) [0.2-2.3] | .69f |
| Comorbidities, No. | |||
| 0 | 242 (53.7) [48.9-58.3] | 248 (55.0) [50.3-60.0] | .89b |
| 1 | 85 (18.9) [15.3-22.8] | 85 (18.8) [15.3-22.8] | |
| ≥2 | 124 (27.5) [23.4-31.9] | 118 (26.2) [22.2-30.5] | |
| Vaccination status at time of infection | |||
| None | 332 (73.6) [69.3-77.6] | 379 (84.0) [80.3-87.3] | <.001b |
| 1 Dose | 24 (5.3) [3.4-7.8] | 18 (4.0) [2.4-6.2] | |
| Second dose ≤3 mo before infection | 30 (6.7) [4.5-9.4] | 35 (7.8) [5.5-10.6] | |
| Second dose >3 mo before infection | 65 (14.4) [11.3-18.0] | 19 (4.2) [2.6-6.5] | |
| Infection status in relation to vaccination | |||
| Infection ≤14 d after second dose | 360 (79.8) [75.8-83.4] | 408 (90.5) [87.4-93.0] | <.001b |
| Infection >14 d after second dose | 91 (20.2) [16.6-24.2] | 43 (9.5) [7.0-12.6] | |
Estimated using the Mann-Whitney test.
Estimated using the χ2 test.
Indian subcontinent includes India, Pakistan, Bangladesh, Nepal, and Sri Lanka.
Other includes 39 nationalities.
Calculated as weight in kilograms divided by height in meters squared. Underweight was considered as a body mass index of less than 18.5; normal, 18.5 to less than 25.0; overweight, 25.0 to less than 30; obesity, 30 or greater.
Estimated using the Fisher exact test.
Persons infected with the Delta variant were more likely to be hospitalized (27.3% [95% CI, 23.2%-31.6%] vs 20.0% [95% CI, 16.4%-24.0%]; P = .01) and to have mild-moderate or severe-critical disease (27.9% [95% CI, 23.8%-32.3%] vs 20.2% [95% CI, 16.6%-24.2%]; P = .01) compared with those infected with the Beta variant (Table 2). There were no statistically significant differences between the groups in hospitalization, intensive care unit admission, need for high-flow oxygen, receipt of mechanical ventilation, or death. However, the number of events were too small for each of these outcomes for a meaningful comparison. Among persons with infection more than 14 days after receiving the second dose of the vaccine (BNT162b2 and mRNA-1673 were administered in >99.5% of vaccinees in Qatar during the study period), there was no significant difference in any of the measures of severity of illness between those with Delta or Beta variant infection. However, among those with infection within 14 days of the second dose, those with Delta variant infection were more likely to be hospitalized (31.1% [95% CI, 26.4%-36.2%] vs 20.3% [95% CI, 16.5%-24.6%]; P < .001) and to have a mild-moderate or severe-critical outcome (31.7% [95% CI, 26.9%-36.8%] vs 20.6% [95% CI, 16.8%-24.8%]; P < .001) compared with those with Beta variant infection (Table 3).
Table 2. Summary of Disease Outcomes in the Groups Infected With the Delta Variant and the Beta Variant.
| Outcome | Persons, No. (%) [95% CI] | P valuea | |
|---|---|---|---|
| Delta variant infection | Beta variant infection | ||
| All persons b | |||
| Hospitalization | 123 (27.3) [23.2-31.6] | 90 (20.0) [16.4-24.0] | .01 |
| Intensive care unit admission | 22 (4.9) [3.1-7.3] | 14 (3.1) [1.7-5.2] | .17 |
| Use of supplemental oxygen | 45 (10.0) [7.4-13.1] | 41 (9.1) [6.6-12.1] | .65 |
| Use of high-flow oxygen | 16 (3.5) [2.0-5.7] | 19 (4.2) [2.6-6.5] | .61 |
| Receipt of mechanical ventilation | 6 (1.3) [0.5-2.9] | 7 (1.6) [0.6-3.2] | .78 |
| Death | 3 (0.7) [0.1-1.9] | 1 (0.2) [0.0-1.2] | .62c |
| Outcome disease statusd | |||
| No hospitalization | 325 (72.1) [67.7-76.2] | 360 (79.8) [75.8-83.4] | .02 |
| Mild-moderate | 101 (22.4) [18.6-26.5] | 70 (15.5) [12.3-19.2] | |
| Severe-critical | 25 (5.5) [3.6-8.1] | 21 (4.7) [2.9-7.0] | |
| Composite positive outcomee | 126 (27.9) [23.8-32.3] | 91 (20.2) [16.6-24.2] | .01 |
| Hospitalized persons f | |||
| Intensive care unit admission | 22 (17.9) [11.6-25.8] | 14 (15.6) [8.8-24.7] | .65 |
| Use of supplemental oxygen | 42 (34.2) [25.8-43.2] | 40 (44.4) [34.0-55.3] | .13 |
| Use of high-flow oxygen | 16 (13.0) [7.6-20.3] | 19 (21.1) [13.2-31.0] | .12 |
| Receipt of mechanical ventilation | 6 (4.9) [1.8-10.3] | 7 (7.8) [3.2-15.4] | .38 |
| Death | 3 (2.4) [0.5-7.0] | 1 (1.1) [0.0-0.6] | .64c |
| Outcome disease status | |||
| Mild-moderate | 98 (79.7) [71.5-86.4] | 69 (76.7) [66.6-84.9] | .60 |
| Severe-critical | 25 (20.3) [13.6-28.5] | 21 (23.3) [15.1-33.4] | |
Estimated using the χ2 test.
In both groups, n = 451.
Estimated using the Fisher exact test.
Mild-moderate disease included hospitalization and/or use of supplemental oxygen; severe-critical disease included any 1 or more of intensive care unit admission, use of high-flow oxygen, receipt of mechanical ventilation, or death.
Composite positive outcome included mild-moderate or severe-critical disease.
In the Delta variant group, n = 123; Beta variant group, n = 90.
Table 3. Summary of Disease Outcomes in Persons Infected With the SARS-CoV-2 Delta or Beta Variant Stratified by Vaccination Status.
| Outcome | Infection >14 d after the second vaccine dose | Infection ≤14 d after the second vaccine dose | ||||
|---|---|---|---|---|---|---|
| Persons, No. (%) [95% CI] | P value | Persons, No. (%) [95% CI] | P value | |||
| Delta variant (n = 91) | Beta variant (n = 43) | Delta variant (n = 360) | Beta variant (n = 408) | |||
| Hospitalization | 11 (12.1) [6.2-20.6] | 7 (16.3) [6.8-30.7] | .51a | 112 (31.1) [26.4-36.2] | 83 (20.3) [16.5-24.6] | <.001a |
| Intensive care unit admission | 1 (1.1) [0.0-6.0] | 0 (0.0) [0.0-8.2] | >.99b | 21 (5.8) [3.7-8.8] | 14 (3.4) [1.9-5.7] | .11a |
| Use of supplemental oxygen | 2 (2.2) [0.3-7.7] | 0 (0.0) [0.0-8.2] | >.99b | 43 (11.9) [8.8-15.8] | 41 (10.1) [7.3-13.4] | .40a |
| Use of high-flow oxygen | 0 (0.0) [0.0-4.0] | 0 (0.0) [0.0-8.2] | NA | 16 (4.4) [2.6-7.1] | 19 (4.7) [2.8-7.2] | .89a |
| Receipt of mechanical ventilation | 0 (0.0) [0.0-4.0] | 0 (0.0) [0.0-8.2] | NA | 6 (1.7) [0.6-3.6] | 7 (1.7) [0.7-3.5] | .96a |
| Death | 0 (0.0) [0.0-4.0] | 0 (0.0) [0.0-8.2] | NA | 3 (0.8) [0.0-2.4] | 1 (0.2) [0.0-1.4] | .35b |
| Outcome disease statusc | ||||||
| No hospitalization | 79 (86.8) [78.1-93.0] | 36 (83.7) [69.3-93.2] | .64b | 246 (68.3) [63.3-73.1] | 324 (79.4) [75.2-83.2] | <.001a |
| Mild-moderate | 11 (12.1) [6.2-20.6] | 7 (16.3) [6.8-30.7] | 90 (25.0) [20.6-29.8] | 63 (15.4) [12.1-19.3] | ||
| Severe-critical | 1 (1.1) [0.0-6.0] | 0 (0.0) [0.0-8.2] | 24 (6.7) [4.3-9.8] | 21 (5.2) [3.2-7.8] | ||
| Composite positive outcomed | 12 (13.2) [7.0-21.9] | 7 (16.3) [6.8-30.7] | .63a | 114 (31.7) [26.9-36.8] | 84 (20.6) [16.8-24.8] | <.001a |
Abbreviation: NA, not applicable.
Estimated using the χ2 test.
Estimated using the Fisher exact test.
Mild-moderate disease included hospitalization and/or use of supplemental oxygen; severe-critical disease included any 1 or more of intensive care unit admission, use of high-flow oxygen, receipt of mechanical ventilation, or death.
Composite positive outcome included mild-moderate or severe-critical disease.
Infection with the Delta variant was independently associated with higher odds of experiencing any adverse outcome (aOR, 2.53; 95% CI, 1.72-3.72) (Table 4). Compared with being unvaccinated, having received 2 vaccine doses within 3 months or more than 3 months before infection was associated with a markedly lower odds of any outcome (mild-moderate or severe-critical disease) (aOR for ≤3 months, 0.24 [95% CI, 0.11-0.56]; aOR for >3 months, 0.14 [95% CI, 0.07-0.29]). Having received a single dose was not associated with a lower risk of a more serious outcome (aOR, 0.94; 95% CI, 0.44-2.02) (Table 4). Other factors associated with a higher odds of any adverse outcome included increasing age (vs 0-19 years) (aOR for 20-39 years, 4.47 [95% CI, 2.09-9.56]; aOR for 40-59 years, 10.26 [95% CI, 4.73-22.26]; aOR for ≥60 years, 9.46 [95% CI, 3.52-25.38]) and presence of comorbidities (aOR for 1-2 comorbidities, 4.22 [95% CI, 2.82-6.32]; aOR for ≥3 comorbidities, 7.14 [95% CI, 3.58-14.23]) (Table 4).
Table 4. Multivariable Logistic Regression With Outcome Disease Status as the Dependent Variable.
| Variable | Any outcome | Severe-critical diseasea | Mild-moderate diseasea | |||
|---|---|---|---|---|---|---|
| aOR (95% CI) | P value | aOR (95% CI) | P value | aOR (95% CI) | P value | |
| Variant | ||||||
| Beta | 1 [Reference] | NA | 1 [Reference] | NA | 1 [Reference] | NA |
| Delta | 2.53 (1.72-3.72) | <.001 | 3.61 (1.65-7.91) | .001 | 2.55 (1.69-3.85) | <.001 |
| Vaccination status at time of infection | ||||||
| None | 1 [Reference] | NA | 1 [Reference] | NA | 1 [Reference] | NA |
| 1 Dose | 0.94 (0.44-2.02) | .87 | 2.49 (0.78-7.93) | .12 | 0.66 (0.27-1.62) | .36 |
| Second dose ≤3 mo before infection | 0.24 (0.11-0.56) | <.001 | NA | NA | 0.30 (0.13-0.69) | .01 |
| Second dose >3 mo before infection | 0.14 (0.07-0.29) | <.001 | 0.03 (0.00-0.23) | .001 | 0.17 (0.08-0.37) | <.001 |
| Age, y | ||||||
| 0-19 | 1 [Reference] | NA | 1 [Reference] | NA | 1 [Reference] | NA |
| 20-39 | 4.47 (2.09-9.56) | <.001 | 7.17 (0.83-61.68) | .07 | 4.37 (1.98-9.68) | <.001 |
| 40-59 | 10.26 (4.73-22.26) | <.001 | 15.24 (1.80-129.06) | .01 | 10.29 (4.56-23.25) | <.001 |
| ≥60 | 9.46 (3.52-25.38) | <.001 | 11.81 (1.17-119.22) | .04 | 9.89 (3.47-28.20) | <.001 |
| Sex | ||||||
| Female | 1 [Reference] | NA | 1 [Reference] | NA | 1 [Reference] | NA |
| Male | 1.63 (1.10-2.43) | .02 | 2.92 (1.23-6.96) | .02 | 1.47 (0.97-2.23) | .07 |
| Nationality | ||||||
| Qatari | 1 [Reference] | NA | 1 [Reference] | NA | 1 [Reference] | NA |
| Indian subcontinent and Sudanb | 1.37 (0.81-2.30) | .24 | 1.36 (0.44-4.18) | .59 | 1.34 (0.78-2.32) | .29 |
| Otherc | 1.75 (1.06-2.88) | .03 | 2.47 (0.87-7.05) | .09 | 1.62 (0.95-2.74) | .08 |
| Body mass indexd | ||||||
| Normal | 1 [Reference] | NA | 1 [Reference] | NA | 1 [Reference] | NA |
| Underweight | 0.22 (0.07-0.69) | .01 | NA | NA | 0.24 (0.08-0.77) | .02 |
| Overweight | 1.00 (0.63-1.59) | .99 | 1.74 (0.66-4.63) | .27 | 0.87 (0.53-1.42) | .57 |
| Obesity | 0.85 (0.52-1.38) | .50 | 1.45 (0.52-4.05) | .48 | 0.76 (0.45-1.27) | .30 |
| Comorbidities, No. | ||||||
| 0 | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA | |
| 1-2 | 4.22 (2.82-6.32) | <.001 | 8.69 (3.31-22.80) | <.001 | 3.84 (2.52-5.88) | <.001 |
| ≥3 | 7.14 (3.58-14.23) | <.001 | 41.74 (11.28-154.46) | <.001 | 5.01 (2.35-10.67) | <.001 |
Abbreviations: aOR, adjusted odds ratio; NA, not applicable.
Mild-moderate disease included hospitalization and/or use of supplemental oxygen; severe-critical disease included any 1 or more of intensive care unit admission, use of high-flow oxygen, receipt of mechanical ventilation, or death.
Indian subcontinent includes India, Pakistan, Bangladesh, Nepal, and Sri Lanka.
Other includes 39 nationalities.
Calculated as weight in kilograms divided by height in meters squared. Underweight was considered as a body mass index of less than 18.5; normal, 18.5 to less than 25.0; overweight, 25.0 to less than 30; obesity, 30 or greater.
We also analyzed the factors associated with the composite outcome of severe-critical disease and mild-moderate disease for both variants separately. Persons with Delta variant infection more than 14 days after the second dose of the vaccine had a significantly lower odds of developing any serious outcome (aOR, 0.11; 95% CI, 0.05-0.24) compared with those who developed infection 14 days or less after the second dose. Persons with Beta variant infection also had numerically lower odds of developing any serious outcome (aOR, 0.38; 95% CI, 0.14-1.01), but this did not reach statistical significance. Vaccination was associated with lower odds of developing mild-moderate disease among persons with Delta variant infection compared with those with Beta variant infection (aOR for Delta variant, 0.14 [95% CI, 0.06-0.33]; aOR for Beta variant, 0.51 [95% CI, 0.19-1.37]; P = .04) (Table 5).
Table 5. Multivariable Logistic Regression With Outcome Disease Status as Dependent Variable Stratified by Variant.
| Variable | Any outcome | Severe-critical diseasea | Mild-moderate diseasea | ||||||
|---|---|---|---|---|---|---|---|---|---|
| aOR (95% CI) | P valueb | aOR (95% CI) | P valueb | aOR (95% CI) | P valueb | ||||
| Delta variant | Beta variant | Delta variant | Beta variant | Delta variant | Beta variant | ||||
| Vaccination status | |||||||||
| Infection ≤14 d after second dose | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA |
| Infection >14 d after second dose | 0.11 (0.05-0.24)c | 0.38 (0.14-1.01) | .06 | 0.02 (0.00-0.21)c | NA | >.99 | 0.14 (0.06-0.33)c | 0.51 (0.19-1.37) | .04 |
| Age, y | |||||||||
| 20-39 | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA |
| 0-19 | 0.15 (0.06-0.42)c | 0.27 (0.07-1.04) | .79 | 0.08 (0.01-0.85)c | NA | >.99 | 0.17 (0.06-0.48)c | 0.35 (0.09-1.39) | .54 |
| 40-59 | 2.44 (1.36-4.40)c | 2.84 (1.51-5.34)c | .65 | 3.52 (0.99-12.48) | 1.79 (0.56-5.71) | .29 | 2.48 (1.33-4.61)c | 3.26 (1.63-6.55)c | .43 |
| ≥60 | 1.32 (0.47-3.75) | 4.04 (1.47-11.10)c | .06 | 1.84 (0.30-11.45) | 2.97 (0.49-17.91) | .76 | 1.29 (0.41-4.01) | 4.27 (1.42-12.82)c | .03 |
| Sex | |||||||||
| Female | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA |
| Male | 1.83 (1.04-3.24)c | 1.50 (0.84-2.69) | .67 | 3.16 (0.82-12.21) | 1.37 (0.43-4.38) | .88 | 1.53 (0.85-2.76) | 1.50 (0.80-2.81) | .53 |
| Nationality | |||||||||
| Qatari | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA |
| Indian subcontinent and Sudand | 0.86 (0.42-1.77) | 2.56 (1.14-5.74)c | .09 | 0.45 (0.09-2.20) | 7.45 (0.76-72.73) | .08 | 0.97 (0.45-2.08) | 2.14 (0.82-4.94) | .27 |
| Othere | 1.91 (0.95-3.84) | 2.10 (0.95-4.64) | .90 | 1.87 (0.44-7.95) | 7.89 (0.89-70.09) | .26 | 1.95 (0.93-4.08) | 1.72 (0.74-3.97) | .51 |
| Body mass indexf | |||||||||
| Normal | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA |
| Underweight | 0.16 (0.04-0.66)c | 0.22 (0.03-2.02) | .88 | NA | NA | NA | 0.18 (0.04-0.75)c | 0.24 (0.03-2.22) | .86 |
| Overweight | 0.75 (0.40-1.43) | 1.18 (0.57-2.43) | .34 | 1.43 (0.34-5.96) | 1.46 (0.34-6.28) | .96 | 0.64 (0.33-1.27) | 1.09 (0.50-2.37) | .31 |
| Obesity | 0.61 (0.31-1.21) | 1.10 (0.52-2.31) | .45 | 0.98 (0.23-4.27) | 1.22 (0.26-5.79) | >.99 | 0.53 (0.25-1.10) | 1.07 (0.48-2.38) | .36 |
| Comorbidities, No. | |||||||||
| 0 | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA | 1 [Reference] | 1 [Reference] | NA |
| 1 | 9.48 (4.81-18.67)c | 1.46 (0.71-2.98) | <.001 | 4.48 (0.82-24.39) | 3.47 (0.78-15.47) | .77 | 9.90 (4.95-19.80)c | 1.15 (0.52-2.54) | <.001 |
| ≥2 | 7.46 (3.73-14.91)c | 3.27 (1.67-6.40)c | .41 | 33.44 (8.31-134.53)c | 8.41 (1.93-36.64)c | .15 | 5.60 (2.65-11.84)c | 2.57 (1.25-5.28)c | .67 |
Abbreviations: aOR, adjusted odds ratio; NA, not applicable.
Mild-moderate disease included hospitalization and/or use of supplemental oxygen; severe-critical disease included any 1 or more of intensive care unit admission, use of high-flow oxygen, receipt of mechanical ventilation, or death.
P value comparing ORs between Beta and Delta variants.
P < .05.
Indian subcontinent includes India, Pakistan, Bangladesh, Nepal, and Sri Lanka.
Other includes 39 nationalities.
Calculated as weight in kilograms divided by height in meters squared. Underweight was considered as a body mass index of less than 18.5; normal, 18.5 to less than 25.0; overweight, 25.0 to less than 30; obesity, 30 or greater.
We compared the baseline characteristics of all persons with Delta (n = 1427) and Beta (n = 5353) variant infection. Those infected with the Beta variant were older and more likely to have comorbidities compared with those with Delta variant infection (eTable in the Supplement). A plot demonstrating the effect of propensity score matching on the distribution of variables is shown in the eFigure in the Supplement.
Discussion
Sporadic reports7,8 have suggested that persons infected with the SARS-CoV-2 Delta variant may be at a higher risk for adverse outcomes compared with those infected with other VOCs, although much still remains unknown. We provide results from a national cohort study in Qatar describing clinical outcomes in persons infected with the Delta variant compared with those in propensity score–matched controls infected with the Beta variant.
We found that persons infected with the Delta variant were more likely to be hospitalized compared with those infected with the Beta variant. Need for supplemental or high-flow oxygen, receipt of mechanical ventilation, and death were not significantly different between the 2 groups. However, the number of events were too small to make a meaningful comparison. A recent study from England7 found a higher risk of hospitalization in patients infected with the Delta variant compared with those infected with the Alpha variant. Unvaccinated persons were at an especially higher risk. Patients infected with the Beta variant were not included in that study. Another smaller study from Singapore8 compared outcomes among patients infected with the Alpha, Beta, and Delta variants using persons infected with other variants as the control group. Although Delta variant infection was associated with a higher risk of a composite outcome of oxygen requirement, intensive care unit admission, and death, the Delta and Beta variant infections were not directly compared. Higher viral load in patients with Delta variant infection may be a potential mechanism conferring higher virulence and poorer outcomes.
In the present study, being fully unvaccinated was associated with a significantly lower risk of poorer outcomes. This was observed for any outcome, mild-moderate disease, and severe-critical disease. Although the benefit was observed in both Delta variant– and Beta variant–infected persons, a comparison of any outcome between Delta variant– and Beta variant–infected persons demonstrated a 2-fold higher risk among those with Beta variant infection. This underscores the importance of vaccination in preventing severe consequences of SARS-CoV-2 infection regardless of the VOC. Although the reported effectiveness of currently available vaccines is somewhat lower against the Delta variant,11 our study provides a rationale for vaccination to prevent the severe consequences of infection.
Increasing age and presence of comorbidities were associated with any adverse outcome, mild-moderate disease, and severe-critical disease even after adjusting for vaccination status. These are well-known risk factors for poor outcomes in patients with SARS-CoV-2 infection. These factors were associated with a higher risk of poor outcomes in persons infected with the Delta variant compared with those infected with the Beta variant.
Strengths and Limitations
Strengths of our study include a large national population, extensive testing, a single testing site, and uniform data collection methods. To mitigate potential bias from an imbalance in baseline risk factors, we conducted robust propensity score matching of the 2 study groups.
This study also has limitations. This was a retrospective study. Variant identification was based on RT-qPCR variant genotyping, and only a subset of the sample was subjected to whole genome sequencing. However, we demonstrated a high level of correlation between genotyping and viral sequencing.
Conclusions
In this cohort study of individuals with COVID-19 in Qatar, infection with the Delta variant was associated with a higher risk of poorer clinical outcomes compared with infection with the Beta variant. Vaccination was associated with significantly lower rates of infection with both variants and especially with significantly lower rates of severe-critical disease.
eTable. Baseline characteristics before propensity score matching.
eFigure. A plot demonstrating the effect of propensity score matching in our study population.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable. Baseline characteristics before propensity score matching.
eFigure. A plot demonstrating the effect of propensity score matching in our study population.