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OBJECTIVES: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19. DESIGN: Phase III double-blind randomised controlled trial. SETTING: Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic. PARTICIPANTS: 3988 healthcare workers with no prior COVID-19 and no contraindication to BCG. INTERVENTION: Randomised 1:1 using a web-based procedure to receive a single 0.1 mL intradermal dose of BCG-Denmark (BCG group, n = 1999) or saline (placebo group, n = 1989). MAIN OUTCOME MEASURES: Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12 months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion). RESULTS: Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6 to 24.5%) compared with the placebo group (19.6%; 95% CI 17.6 to 21.5%); adjusted difference +3.0% points (95% CI 0.2 to 5.8%; p = 0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95% CI 9.5 to 12.4%) compared with 9.6% in the placebo group (95% CI 8.3 to 11.1%); adjusted difference +1.3% points (95% CI -0.7 to 3.3%, p = 0.2). Breakthrough COVID-19 (post COVID-19 vaccination) and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95% CI 0.60 to 4.02, p = 0.4) and two deaths due to COVID-19, both in the placebo group. CONCLUSIONS: Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among healthcare workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327206.
Assuntos
Vacina BCG , COVID-19 , Pessoal de Saúde , SARS-CoV-2 , Humanos , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Masculino , Feminino , Adulto , Método Duplo-Cego , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Vacinação , Austrália/epidemiologia , Brasil/epidemiologia , Reino Unido/epidemiologia , Espanha/epidemiologiaRESUMO
Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.
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The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6-11.5) and 56.8% (95% CI, 56.3-57.3) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9-80.7) and 86.0% (95% CI, 84.5-87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.
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Vacinas contra COVID-19 , COVID-19 , Adulto , Vacina BNT162 , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Casos e Controles , Humanos , Vacinas de Produtos InativadosRESUMO
Diagnosis of pulmonary tuberculosis is usually achieved by testing sputum for presence of Mycobacterium tuberculosis by microscopy, culture or nucleic acid amplification tests. However, many individuals are unable to produce sputum, particularly early in the course of illness. Studies have reported that oral swabs, assayed by nucleic acid amplification tests, may be a suitable substitute or complement to sputum testing. To determine whether this method could be useful of case finding, in which bacillary load is often lower, we evaluated it in the setting of a mass tuberculosis screening study in prison inmates in Brazil. For this sub-study, we enrolled 128 individuals with pulmonary tuberculosis confirmed by sputum Xpert testing, and 128 controls who tested negative by sputum culture and Xpert. We collected two oral swabs by participant, prior to starting treatment. Swabs were collected from the tongue by brushing along the surface for 10 times. The sensitivity of a single oral swab was 43% (N = 55/128; 95% CI: 34-52%). Using two consecutive oral swabs the sensitivity increased to 51% (N = 66/128; 95% CI: 43-60%). The specificity was 100% (128/128). In participants with high mycobaterial load in the sputum, the combined sensitivity was 90% (N = 9/10). In the participants with medium mycobaterial load in the sputum, the combined sensitivity was 79% (N = 23/29). In the participants with low or very low mycobaterial load in the sputum, the combined sensitivity was 38% (N = 34/89). Our data suggest that oral swab sampling, assayed by Xpert, has comparable sensitivity to sputum in participants with high and medium mycobacterial load in the sputum. However, 70% (89/128) of individuals identified through our mass screening study (Carbone et al.) had detection number low or very low in their sputum. In this population, oral swab testing may not have sufficient sensitivity as currently performed. Further studies are needed to identify alternative non-sputum sampling strategies in this population.
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O sistema proposto visa avaliar, qualitativa e quantitativamente, o comportamento de diferentes técnicas de síntese pós-osteotomia em metatarsos, mediante aplicação de esforços conhecidos em suas extremidades.
The equipment measures the deviation of the first metatarsal head as a result of forces applied through its plantar surface. Load displacement curves were obtained and the stiffness of severa! metatarsal osteotomy j!xation techniques were then compared