Submitted:
16 April 2025
Posted:
21 April 2025
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Abstract
Keywords:
- This prospective cohort followed participants for up to 34 months encompassing eight SARS-CoV-2 variant periods
- The use of modified survival analysis permitted the inclusion of both first and subsequent SARS-CoV-2 infections in the analysis of factors associated with infection
- Self-collected dried blood spot samples were used to assess serological response to vaccines and infections
- Exposure information from participants without symptoms who were negative for, or not tested for, SARS-CoV-2 was used as comparators to infected participants
- Participants who withdrew may be dissimilar to those who chose to continue in the study
1. Introduction
2. Methods
2.1. Setting
2.2. Data Collection
2.3. Definitions
2.4. Data Structuring and Analysis
3. Results
3.1. Cohort Characteristics
- (1)
- HIV/AIDS or other immune suppressing disease or immunosuppressive medication for >7 consecutive days including prednisone (>20 mg/day), methotrexate, cyclosporine, imuran, azathioprine tacrolimus, or other
- (2)
- office and clerical staff, superintendent, human resources, finance, planner, audio-visual or computer technicians, bus driver, building maintenance/custodial, cafeteria/lunchroom staff
- (3)
- psychologist, social worker, therapist, school nurse
- (4)
- as defined by the first character of the postal code
3.2. Risk Factors for SARS-CoV-2 Infections
- (5)
- Positive by respiratory swab (self-reported) or DBS sample (anti-nucleocapsid and anti-RBD and/or anti-spike IgG levels above threshold of detection); n=9/384 or 2.3% of participants with previous positive results were detected by serology alone
- (6)
- Close contact (≤2 metres for >2 minutes) with someone with SARS-CoV-2 in previous 14 days
- (7)
- Close contact not listed above (e.g., extended family member, friend, or other)
- (8)
- Deaths attributed to COVID-19 in province, with 14-day lag, used as a proxy for force of infection
3.3. RBD Levels as Correlates of Protection
- (1)
- Cox proportional hazard model using Prentice-William-Peterson extension; adjusted for age, gender, health status, number of doses of COVID-19 vaccines, and whether they had tested positive for SARS-CoV-2 prior to the blood sample; stratified by time since vaccination or SARS-CoV-2 infection, and using previous SARS-CoV-2 history as a time-varying covariate
- (2)
- Adjusted as above less a) whether they had tested positive for SARS-CoV-2 prior to the blood sample as a covariate and b) history of SARS-CoV-2 infection as a time-varying covariate
4. Discussion
4.1. Strengths and Limitations
4.2. Conclusions
Supplementary Materials
Funding
Acknowledgements
Data Sharing
Ethics Statement
References
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| Demographic Variable | Risk Factor Analysis (N=3155) |
Serological Analysis (N=2977) |
|---|---|---|
| Age, median years (IQR) | 46 (40, 52) | 46 (40, 52) |
| Gender/sex Female Male Other |
2688 (85.2) 458 (14.5) 9 (0.3) |
2534 (85.1) 435 (14.6) 8 (0.3) |
| Household size, median (IQR) | 3 (2, 4) | 3 (2, 4) |
| Caucasian (vs other) | 2963 (94.0) | 2805 (94.2) |
| Health status Fair or poor Good Very good Excellent |
140 (4.4) 795 (25.2) 1494 (47.3) 726 (23.0) |
140 (4.7) 741 (24.9) 1409 (47.3) 687 (23.1) |
| At least one chronic health condition | 803 (25.6) | 753 (25.3) |
| Immune compromising condition/medication1 | 86 (2.7) | 80 (2.7) |
| Eye glasses No Reading and distance Reading or distance Contacts |
754 (23.9) 1326 (42.0) 837 (26.5) 238 (7.5) |
711 (23.9) 1236 (41.6) 796 (26.8) 227 (7.6) |
| Use refillable drink container Never < Once/month Several times/month Several times/week Most days |
118 (3.7) 69 (2.2) 106 (3.4) 241 (7.6) 2621 (83.1) |
104 (3.5) 64 (2.2) 96 (3.2) 229 (7.7) 2475 (83.4) |
| Hands to face frequency Never 1-2/day 3-5/day >5/day |
379 (12.0) 1345 (42.6) 720 (22.8) 711 (22.5) |
353 (11.9) 1289 (43.4) 670 (22.5) 661 (22.2) |
| Tobacco smoking Never Former Current |
2406 (76.3) 612 (19.4) 137 (4.3) |
2270 (76.3) 588 (19.7) 119 (4.0) |
| Public school board (vs private) | 3026 (95.9) | 2861 (96.2) |
| Education level Secondary or less College diploma Bachelor’s degree Teaching certificate Master’s degree Doctoral degree |
44 (1.4) 227 (7.2) 421 (13.3) 1735 (55.0) 680 (21.5) 48(1.5) |
43 (1.4) 210 (7.1) 396 (13.3) 1645 (55.3) 637 (21.4) 46 (1.5) |
| Occupation Teacher Educational assistant Early childhood educator Principal/vice principal Administrative/support2 Professional3 |
2565 (81.3) 181 (5.7) 70 (2.2) 117 (3.7) 113 (3.6) 109 (3.4) |
2428 (81.6) 161 (5.4) 69 (2.3) 105 (3.6) 110 (3.7) 103 (3.5) |
| Students in school <100 100-399 400-699 700+ Not applicable (e.g., board office) |
94 (3.0) 1031 (32.7) 926 (29.3) 887 (28.1) 217 (6.9) |
90 (3.0) 997 (33.5) 896 (30.1) 874 (29.4) 116 (3.9) |
| Level of contact with students No close contact In same room but >2 metres distance In same room and <2 metres distance Physical contact |
328 (10.4) 422 (13.4) 1685 (53.4) 720 (22.8) |
208 (7.0) 318 (10.7) 1688 (56.7) 762 (25.6) |
| Level of contact with coworkers No close contact In same room but >2 metres distance In same room and <2 metres distance Physical contact |
344 (10.9) 1355 (43.0) 1340 (42.5) 116 (3.7) |
345 (11.6) 1316 (44.2) 1203 (40.4) 113 (3.8) |
| Region of residence in Ontario4 East Central Toronto Southwest North |
559 (17.7) 1084 (34.5) 626 (19.8) 729 (23.1) 157 (5.0) |
550 (18.5) 1028 (34.5) 565 (19.0) 690 (23.2) 144 (4.8) |
| Covariate | All Participants (n=1909 Positive) aHR (95% CI) |
No Previous Infection(s) (n=1525 Positive) aHR (95% CI) |
SARS-CoV-2 Previously (n=384 Positive) aHR (95% CI) |
|---|---|---|---|
| Doses of vaccine: <2 2 3 4 ≥5 |
Referent 1.15 (0.55, 2.44) 0.24 (0.11, 0.50)‡ 0.14 (0.07, 0.30)‡ 0.14 (0.06, 0.30)‡ |
Referent 0.84 (0.49, 1.44) 0.08 (0.04, 0.14)‡ 0.03 (0.02, 0.06)‡ 0.02 (0.01, 0.05)‡ |
Referent 0.50 (0.16, 1.55) 0.43 (0.15, 1.27) 0.29 (0.10, 0.87)* 0.32 (0.10, 0.97)* |
| SARS-CoV-2 previously1 Not infected |
0.05 (0.04, 0.07)‡ Referent |
NA | NA |
| Age group: 20-29 30-39 40-49 50-59 ≥60 |
Referent 0.64 (0.47, 0.88)† 0.61 (0.45, 0.83)† 0.58 (0.43, 0.79)‡ 0.61 (0.43, 0.85)† |
Referent 0.57 (0.39, 0.83)† 0.59 (0.41, 0.86)† 0.55 (0.38, 0.79)† 0.53 (0.35, 0.81)† |
Referent 1.10 (0.46, 2.64) 0.94 (0.40, 2.19) 1.02 (0.44, 2.40) 1.11 (0.46, 2.91) |
| Caucasian ancestry Other |
0.82 (0.71, 0.96)† Referent |
0.87 (0.73, 1.02) Referent |
0.68 (0.46, 1.00)* Referent |
| No close contact2 Household member Coworker or student Other person3 More than one of the above |
Referent 1.53 (1.38, 1.70)‡ 1.21 (1.04, 1.41)* 0.94 (0.55, 1.62) 1.45 (1.29, 1.63)‡ |
Referent 1.34 (1.17, 1.53)‡ 1.10 (0.95, 1.29) 1.25 (0.70, 2.24) 1.29 (1.12, 1.49)‡ |
Referent 2.20 (1.65, 2.94)‡ 1.67 (1.31, 2.13)‡ 0.29 (0.03, 2.46) 2.16 (1.62, 2.89)‡ |
| Mortality rate, in province4 | 1.31 (1.28, 1.35)‡ | 1.36 (1.32, 1.40)‡ | 1.66 (1.41, 1.96)‡ |
| Anti-RBD Level (in BAU/mL) |
All Participants1 (n=15991 Samples) aHR (95% CI) |
No Previous Infection(s)2 (n=11584 Samples) aHR (95% CI) |
SARS-CoV-2 Previously2 (n=4407 Samples) aHR (95% CI) |
|---|---|---|---|
| Below threshold of detection 10-759 760-2289 2290-5849 ≥5850 |
Referent 0.88 (0.51, 1.52) 0.78 (0.45, 1.36) 0.66 (0.38, 1.15) 0.40 (0.23, 0.72)† |
Referent 0.80 (0.44, 1.46) 0.72 (0.40, 1.32) 0.63 (0.34, 1.16) 0.39 (0.21, 0.73)† |
Referent 1.98 (0.44, 8.97) 1.14 (0.24, 5.37) 0.74 (0.16, 3.48) 0.51 (0.11, 2.42) |
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