Table 1.
Participant baseline characteristics and immune events during follow-up.
|
Baseline Characteristics Cells contain n (% of N) unless stated otherwise |
Total-analysis population | Randomised population | ||||
|
Placebo
N = 480 |
BCG
N = 490 |
p 1,2 |
Overall
N = 970 |
Overall
N = 1511 |
p 1,3 | |
| Age in years, mean (SD) | 43.0 (12.6) | 42.0 (12.6) | 0.208 | 42.5 (12.6) | 42.0 (12.7) | 0.366 |
| Female | 355 (74.0) | 369 (72.3) | 0.683 | 724 (74.7) | 1122 (74.3) | 0.868 |
| Smoking status | 0.143 | 0.258 | ||||
| Current | 31 (6.5) | 34 (6.9) | 65 (6.7) | 123 (8.1) | ||
| Former | 136 (28.3) | 166 (33.9) | 302 (31.1) | 436 (28.9) | ||
| Never | 313 (65.2) | 290 (59.2) | 603 (62.2) | 952 (63.0) | ||
| Work-related exposure 4 | 0.936 | 0.492 | ||||
| Low | 72 (15.0) | 76 (15.5) | 148 (15.3) | 213 (14.1) | ||
| Medium | 121 (25.2) | 119 (24.3) | 240 (24.7) | 356 (23.6) | ||
| High | 287 (59.8) | 295 (60.2) | 582 (60.0) | 942 (62.3) | ||
| History of BCG vaccination | 83 (17.3) | 91 (18.6) | 0.663 | 174 (17.9) | 256 (16.9) | 0.559 |
| Past TB test results 5 | 0.135 | 0.491 | ||||
| Tested negative | 320 (66.7) | 320 (66.7) | 640 (66.0) | 1016 (67.2) | ||
| Tested positive | 49 (10.2) | 45 (9.2) | 94 (9.7) | 136 (9.0) | ||
| Never tested | 109 (22.7) | 115 (23.5) | 224 (23.1) | 347 (23.0) | ||
| Unknown | 2 (0.4) | 10 (2.0) | 12 (1.2) | 12 (0.8) | ||
| Respiratory infection in winter 2019–2020 | 0.310 | 0.748 | ||||
| No | 349 (72.7) | 364 (74.3) | 713 (73.5) | 1090 (72.1) | ||
| Yes, with fever | 35 (7.3) | 44 (9.0) | 79 (8.1) | 127 (8.4) | ||
| Yes, without fever | 96 (20.0) | 82 (16.7) | 178 (18.3) | 294 (19.5) | ||
| Influenza vaccination in winter 2020–2021 6 | 0.239 | <0.001 | ||||
| Yes | 273 (56.9) | 255 (52.0) | 528 (54.4) | 697 (46.1) | ||
| No | 142 (29.6) | 169 (34.5) | 311 (32.1) | 428 (28.3) | ||
| Missing | 65 (13.5) | 66 (13.5) | 131 (13.5) | 386 (25.5) | ||
| Influenza vaccination prior to follow-up | 278 (57.9) | 282 (57.6) | 0.960 | 560 (57.7) | 872 (57.7) | 1.000 |
| Any other vaccination in past year 7 | 51 (10.6) | 54 (11.0) | 0.924 | 105 (10.8) | 162 (10.7) | 0.988 |
| Current use of anti-hypertensive medication | 33 (6.9) | 28 (5.7) | 0.540 | 61 (6.3) | 99 (6.6) | 0.860 |
| History of cardiovascular disease | 14 (2.9) | 9 (1.8) | 0.371 | 23 (2.4) | 34 (2.3) | 0.953 |
| Current use of anti-diabetic medication | 2 (0.4) | 3 (0.6) | 1.000 | 5 (0.5) | 9 (0.6) | 1.000 |
| History of asthma | 35 (7.3) | 34 (6.9) | 0.929 | 69 (7.1) | 101 (6.7) | 0.740 |
| History of hay fever | 130 (27.1) | 158 (32.2) | 0.091 | 288 (29.7) | 441 (29.2) | 0.823 |
| History of other pulmonary disease | 12 (2.5) | 11 (2.2) | 0.960 | 23 (2.4) | 32 (2.1) | 0.781 |
| Any lung disease (previous three combined) | 154 (32.1) | 175 (35.7) | 0.260 | 329 (33.9) | 497 (32.9) | 0.628 |
|
Immune Events Cells contain n (% of N) unless stated otherwise |
Total-analysis population | Randomised population | ||||
|
Placebo
N = 480 |
BCG
N = 490 |
p 1,2 |
Overall
N = 970 |
Overall
N = 1511 |
p 1,3 | |
| Number of immune events 8 | 0.323 | <0.001 | ||||
| 0 | 218 (45.4) | 235 (48.0) | 453 (46.7) | 679 (46.0) | ||
| 1 | 93 (19.4) | 94 (19.2) | 187 (19.3) | 487 (33.0) | ||
| 2 | 127 (26.5) | 133 (27.1) | 260 (26.8) | 216 (14.6) | ||
| 3 | 42 (8.8) | 28 (5.7) | 70 (7.2) | 94 (6.4) | ||
| Immune event type | 0.614 | <0.001 | ||||
| None | 218 (45.4) | 235 (48.0) | 453 (46.7) | 680 (45.0) | ||
| Infection 9 | 62 (12.9) | 61 (12.4) | 123 (12.7) | 158 (10.5) | ||
| Vaccine 1 dose | 31 (6.5) | 33 (6.7) | 64 (6.6) | 177 (11.7) | ||
| Vaccine 2 doses | 112 (23.3) | 118 (24.1) | 230 (23.7) | 320 (21.2) | ||
| Infection + 1 dose | 15 (3.1) | 15 (3.1) | 30 (3.1) | 54 (3.6) | ||
| Infection + 2 doses | 42 (8.8) | 28 (5.7) | 70 (7.2) | 86 (5.7) | ||
| COVID-19 vaccine product and dose 10 | 0.148 | 0.002 | ||||
| None | 280 (58.3) | 296 (60.4) | 576 (59.4) | 868 (57.4) | ||
| mRNA 1 dose | 30 (6.2) | 25 (5.1) | 55 (5.7) | 125 (8.3) | ||
| mRNA 2 doses | 154 (32.1) | 146 (29.8) | 300 (30.9) | 416 (27.5) | ||
| Vector 1 dose | 13 (2.7) | 23 (4.7) | 36 (3.7) | 86 (5.7) | ||
| Vector 2 doses | 0 (0.0) | (0.0) | (0.0) | 7 (0.5) | ||
| Unknown 1 dose | 3 (0.6) | 0 (0.0) | 3 (0.3) | 9 (0.6) | ||
| Had SARS-CoV-2 infection during follow-up 11 | 119 (24.8) | 104 (21.2) | 0.214 | 223 (21.2) | 298 (19.7) | 0.109 |
| Infection severity 12 | 0.727 | 0.541 | ||||
| No infection | 361 (75.2) | 386 (78.8) | 747 (77.0) | 1213 (77.9) | ||
| Asymptomatic | 15 (3.1) | 18 (3.7) | 33 (3.4) | 42 (2.8) | ||
| Very Mild | 65 (13.5) | 55 (11.2) | 120 (12.4) | 163 (10.8) | ||
| Mild | 25 (5.2) | 19 (3.9) | 44 (4.5) | 61 (4.0) | ||
| Moderate | 1 (0.2) | 1 (0.2) | 2 (0.2) | 3 (0.2) | ||
| Unknown | 13 (2.7) | 11 (2.2) | 24 (2.5) | 29 (1.9) | ||
| Acute duration of infection 13 | 0.401 | 0.908 | ||||
| 0 days/no infection | 377 (78.5) | 405 (82.7) | 782 (80.6) | 1251 (82.8) | ||
| 0–1 weeks | 20 (4.2) | 9 (1.8) | 29 (3.0) | 44 (2.9) | ||
| 1–2 weeks | 22 (4.6) | 23 (4.7) | 45 (4.6) | 61 (4.0) | ||
| 2–3 weeks | 17 (3.5) | 15 (3.1) | 32 (3.3) | 42 (2.8) | ||
| 3–4 weeks | 9 (1.9) | 8 (1.6) | 17 (1.8) | 20 (1.3) | ||
| 4+ weeks | 10 (2.1) | 5 (1.0) | 15 (1.5) | 18 (1.2) | ||
| Lingering | 10 (2.1) | 12 (2.4) | 22 (2.3) | 34 (2.3) | ||
| Ongoing/UNK | 15 (3.1) | 13 (2.7) | 28 (2.9) | 41 (2.7) | ||
| Long COVID | 0.489 | 0.975 | ||||
| No | 106 (89.1) | 87 (83.7) | 193 (86.5) | 256 (85.9) | ||
| Yes | 8 (6.7) | 11 (10.6) | 19 (8.5) | 27 (5.0) | ||
| Unknown | 5 (4.2) | 6 (5.8) | 11 (4.9) | 15 (9.1) | ||
| Long-term loss of smell/taste | 0.208 | 0.711 | ||||
| No | 112 (94.1) | 99 (95.2) | 211 (94.6) | 278 (93.3) | ||
| Yes | 5 (4.2) | 1 (1.0) | 6 (2.7) | 12 (4.0) | ||
| Unknown | 2 (1.7) | 4 (3.8) | 6 (2.7) | 8 (2.7) | ||
Abbreviations: BCG = Bacillus Calmette–Guérin vaccine; M = month; SD = standard deviation; TB = tuberculosis. p-values in bold indicate p < 0.05. 1 Chi-squared tests for categorical variables and Wilcoxon rank sum test for continuous variables. 2 Statistical test comparing baseline characteristics between the BCG and placebo group in the total-analysis population. 3 Statistical test comparing baseline characteristics between the total analysis (N = 970) and randomised populations (N = 1511). 4 Work-related exposure is a combination of participants expected to work in a COVID-19 ward and the percentage of work hours with direct patient contact (Supplementary Methods). 5 Tuberculosis tests include the Mantoux and/or TB QuantiFERON tests. A person who tested positive could have tested positive on either or both tests. 6 Only the missing category is statistically significantly different for the randomised and total-analysis populations. 7 Includes DTaP-IPV, hepatitis A, hepatitis B, yellow fever, typhoid, rabies, mumps-measles-rubella, meningococcal, pneumococcal, Haemophilus influenza type B, Ebola, tick-borne encephalitis, human papillomavirus, and unknown. 8 An immune event is considered to be either one natural infection or one dose of a COVID-19 vaccine. 9 No-one in the total-analysis population, and four persons in the randomised population, experienced more than one infection (two each). 10 COVID-19 vaccines available in The Netherlands during the study period are listed in the methods. In addition, one person received an experimental mRNA vaccine by CureVac N.V. in a clinical trial setting. That vaccine was never marketed due to insufficient efficacy, but the person was included in the mRNA vaccines group. 11 A natural infection was defined as a reported positive test (by the participants through the diary app) or identified by serology (evidence of anti-S1 at sampling round 1 or both anti-S1 and anti-N at sampling round 2). None of the participants in the total-analysis population reported a positive PCR test prior to follow-up at baseline. 12 Participants with an unsure infection status at M12 (never reported a positive test and/or seropositive for anti-N but not anti-S1 at M12; n = 36) were considered as never having had an infection during follow-up in the randomised population and were removed from the total-analysis population. 13 Participants who never had an infection during follow-up are included in the 0 days/no infection category.