Table 1.
Details of 11 Published Trials of BCG Vaccination for Protection Against Coronavirus Disease 2019
| Location; Trial Name; Authors |
Participant Details (Previous BCG Vaccine Rate) |
Total No. Enrolled (Randomization Ratio) |
Intervention: BCG Strain | Control Intervention | Follow- up Duration |
Primary Outcomea | Cases or Days, No. (%) | Reported Summary Measure | |
|---|---|---|---|---|---|---|---|---|---|
| BCG Group |
Control Group | ||||||||
| Poland; “Polish trial”; Czajka et al [16] |
HCWs aged >25 y (100% presumed) |
354 (1:1) |
Poland BCG-10 |
Saline | 3 mo | COVID-19 cases (PCR confirmed) |
38
(22.6) |
44 (25.3) |
“No significant correlation” |
| Brazil; “Brazilian revaccination trial”; Dos Anjos et al [17] |
HCWs with previous BCG (100% confirmed) |
138 (1:1) |
Russia 361-I, SII |
None | 180 d | COVID-19 cases (PCR/serology confirmed) |
8
(12.5) |
11 (16.4) |
“Did not reach statistical significance” |
| Netherlands; BCG-CORONA; Ten Doesschate et al [20] |
HCWs (17%) |
1511 (1:1) |
Denmark 1331, SSI |
Saline | Median, 358 d |
Duration of unplanned absenteeism for any illness, including quarantine (% of planned workdays) |
3443 d
(2.8) |
3298 d (2.7) |
Adjusted risk ratio, 0.94 (95% CrI, .78–1.15) |
| Secondary outcome: COVID-19 cases (symptomatic and PCR/RAT confirmed) |
102
(14.2) |
108 (15.2) |
Adjusted HR 0.94 (95% CI .72–1.13) |
||||||
| South Africa; “South African trial”; Upton et al [22] |
HCWs (100% presumed) |
1000 (1:1) |
Denmark 1331, SSI |
Saline | 52 wk | Hospitalization due to COVID-19 |
10 (2) |
5
(1) |
HR 2.0 (95% CI, .69–5.9) |
| Secondary outcome: COVID-19 cases (PCR/antigen confirmed) |
98 (19.6) |
92
(18.4) |
HR, 1.08 (95% CI, .82–1.42) |
||||||
| Greece; ACTIVATE-2; Tsilika et al [21] |
Adults aged ≥50 y with comorbid conditions (unknown) |
301 (1:1) |
Russia 361-I, SII |
Saline | 3 mo/6 mo | COVID-19 cases (combination of “possible,” “probable,” and “definitive”symptoms and/or molecularly confirmed) in first 3 mo |
2
(1.4) |
10 (6.5) |
P = .09 |
| USA (existing trial); “US trial”; Faustman et al [26] |
Type 1 diabetes mellitus (0%) |
144 (2 BCG: 1 placebo) |
Japan Tokyo-172 (≥3 doses) |
Saline | 15 mo | COVID-19 cases (symptomatic and serology ± PCR confirmed) |
1
(1.0) |
6 (12.5) |
Vaccine efficacy, 92% (P = .006) |
| Netherlands; BCG-CORONA-ELDERLY; Moorlag et al [18] |
Adults aged ≥60 y (27%) | 2014 (1:1) |
Denmark 1331, SSI |
Saline | 12 mo | Clinically relevant respiratory tract infections requiring medical intervention |
29 (2.9) |
24
(2.4) |
Subdistribution HR, 1.26 (98.2% CI, .65–2.44) |
| Secondary outcome: COVID-19 cases (PCR confirmed) |
51 (5.1) |
48
(4.8) |
Subdistribution HR, 1.05 (95% CI, .71–1.56) | ||||||
| India; BRIC; Sinha et al [19] |
Adults aged 18–60 y with comorbid conditions (unknown) |
495 (1:1) |
Russia SII |
Saline | 9 mo | COVID-19 cases (CB-NAAT-confirmed) |
18 (7.3) |
17
(6.8) |
OR, 1.08 (95% CI, .54–2.14) |
| COVID-19 cases (“probable”; symptomatic only) |
15
(6.1) |
36 (14.5) |
OR, 0.38 (95% CI, .20–.72) |
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| Netherlands; BCG-PRIME; Koekenbier et al [24] |
Adults aged ≥60 y with comorbid conditions (15%) | 6112 (1:1) |
Denmark | Saline | 6 mo | COVID-19 cases (symptomatic and PCR/antigen/imaging confirmed) |
129 (4.2) |
115
(3.8) |
Subdistribution HR, 1.12 (95% CI, .87–1.44) |
| Brazil; ProBCG; Santos et al [25] |
HCWs (93%) |
278 (1:1) |
Moreau/Russia SII | Saline | 6 mo | COVID-19 cases (PCR/serology confirmed) |
12
(0.52) b |
17 (0.75)b |
HR, 0.65 (95% CI, .31–1.39) |
| Australia, UK, Brazil, Netherlands, Spain; BRACE; Pittet et al [23] |
HCWs (77%) |
3988 (1:1) |
Denmark 1331, AJV |
Saline | 6 mo/12 mo | COVID-19 cases (symptomatic and PCR/RAT/serology confirmed) in first 6 mo |
132 (14.7)c |
106
(12.3)c |
Adjusted probability difference, +2.4% (95% CI −.7%–5.5%) |
| Severe COVID-19 cases (hospitalized/nonhospitalized) in first 6 mo |
75 (7.6)c |
61
(6.5)c |
Adjusted probability difference, +1.1% (95% CI, −1.2% to 3.5%) |
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Bold text has been used to indicate the group with the more favourable outcome.
Abbreviations: AJV, AJ Vaccines; CB-NAAT, cartridge-based nucleic acid amplification test; CI, confidence interval; COVID-19, coronavirus disease 2019; CrI, credible interval; HCWs, healthcare workers; HR, hazard ratio; OR, odds ratio; PCR, polymerase chain reaction; RAT, rapid antigen test; SII, Serum Institute of India; SSI, Statens Serum Institute.
aSecondary outcomes are noted for trials in which COVID-19 cases were not reported as the primary outcome.
bIncidence as reported by the trial, based on person-days of observation.
cAdjusted estimated percentage in 6 months (adjusted for stratification factors used at randomization: age, geographic location, and presence of comorbid conditions).