Table 1.
Randomized controlled trials (RCTs) on evaluating BCG vaccination effectiveness against COVID-19.
| NCT number (reference) | Study Design | Participants characteristics | Intervention | Follow-up | Results | TB status | ||
|---|---|---|---|---|---|---|---|---|
| Mean Age (Year) | Total number (Male, %) | BCG stain and dosage | Placebo | |||||
| NCT04435379 (17) | Phase 3 mRCT | 67.3 | 2025 (52.9) | VPM1002, 2–8 × 105 CFUs | Saline solution | 240 days | VPM1002 vaccination is safe and seems to protect elderly individuals from severe respiratory disease. | Individuals with ATB or LTBI were excluded |
| NCT04414267 (18) | Phase 3 sRCT | 69 | 301 (67.8) | 0.1 mL BCG Moscow | Saline solution | 6 months | BCG vaccination can offer some protection against COVID-19 among individuals over 50 years old with underlying health conditions. | Individuals with ATB or LTBI were excluded |
| RBR-4kjqtg (22) | Phase 2 sRCT | 43 | 131 (23.7) | 0.1 mL BCG Moscow | – | 180 days | A second BCG Moscow vaccination was linked to a reduced rate of COVID-19 infections, although the findings were not statistically significant. | Individuals with ATB or LTBI were excluded |
| NCT04417335 (23) | Phase 3 sRCT | 67 | 2014 (52.5) | 0.1 mL BCG Danish strain | Saline solution | 12 months | BCG vaccination did not impact the occurrence of SARS-CoV-2 infection among older adult volunteers. However, it did enhance the cytokine responses produced by both influenza and SARS-CoV-2, as well as lead to stronger antibody titers following COVID-19 infection. | Individuals with ATB or LTBI were excluded |
| NCT04328441 (20) | Phase 3 mRCT | 42 | 1511 (25.7) | 0.1 mL BCG Danish strain | Saline solution | 26 weeks | BCG vaccination offers some defense against potential COVID-19 infection in patients over 50 years old who have underlying health conditions. | Individuals with ATB or LTBI were excluded |
| NCT04328441 (21) | Phase 3 mRCT | 1309 (25.6) | 0.1 mL BCG Danish strain 1331 | Saline solution | 12 months | BCG vaccination did not reduce the incidence of SARS-CoV-2 infection in HCWs, nor did it reduce the duration or severity of infection, but it may enhance antibody production during SARS-CoV-2 infection. | Individuals with ATB or LTBI were excluded | |
| NCT04379336 (19) | Phase 3 mRCT | 39 | 1000 (29.6) | 0.1 mL BCG Danish strain | Saline solution | 52 weeks | BCG did not protect HCWs from SARS-CoV-2 infection or related severe COVID-19 disease and hospitalization. | Individuals with ATB were excluded |
| NCT04648800 (24) | Phase 3 mRCT | 45 | 342 (19.3) | 0.1 mL BCG Moreau strain | Saline solution | 3 months | There was no meaningful association found between the frequency of suspected COVID-19 incidents and BCG-10 vaccination, tuberculin test results, or the number of scars. | Individuals with a TB history were excluded |
| NCT04659941 (16) | Phase 2b mRCT | Groups | 264 (20.4) | 0.1 mL BCG Moreau and Moscow strains | Sterile 0.9% NaCl | 180 days | BCG did not demonstrate a protective hazard ratio against COVID-19. | Individuals with ATB or LTBI were included |
| CTRI/2020/07/026668 (25) | Phase 3 mRCT | 43 | 495 (52.1) | 0.1 mL BCG, 0.2 and 0.8 million CFUs | 0.1 ml of normal saline | 6 months | BCG vaccination did not significantly reduce the incidence of PCR-positive COVID-19 infection but did significantly reduce the incidence of clinically diagnosed COVID-19 infection in high-risk population. | Individuals with ATB or LTBI were not determined |
CFU, colony forming unit; HCWs, health care workers; NCT, Clinical trials registration number; VPM1002 vaccine is a genetically modified BCG; sRCT, single center randomized controlled trial; mRCT, multicenter randomized controlled trial.