Fetal death as an outcome of acute respiratory distress in pregnancy, during the COVID-19 pandemic: a population-based cohort study in Bahia, Brazil.

BACKGROUND: Fetal loss is one of the most serious adverse outcomes of pregnancy. Since the onset of the COVID-19 pandemic, Brazil has recorded an unprecedented number of hospitalizations of pregnant women due to acute respiratory distress (ARD), thereby, we aimed to assess the risk of fetal deaths associated to ARD during pregnancy in Bahia state, Brazil, in the context of the COVID-19 pandemic. METHODS: This is an observational population-based retrospective cohort study, developed with women at or after 20 weeks of pregnancy, residents in Bahia, Brazil. Women who had acute respiratory distress (ARD) in pregnancy during the COVID-19 pandemic (Jan 2020 to Jun 2021) were considered 'exposed'. Women who did not have ARD in pregnancy, and whose pregnancy occurred before the onset of the COVID-19 pandemic (Jan 2019 to Dec 2019) were considered 'non-exposed'. The main outcome was fetal death. We linked administrative data (under mandatory registration) on live births, fetal deaths, and acute respiratory syndrome, using a probabilistic linkage method, and analyzed them with multivariable logistic regression models. RESULTS: 200,979 pregnant women participated in this study, 765 exposed and 200,214 unexposed. We found four times higher chance of fetal death in women with ARD during pregnancy, of all etiologies (adjusted odds ratio [aOR] 4.06 confidence interval [CI] 95% 2.66; 6.21), and due to SARS-CoV-2 (aOR 4.45 CI 95% 2.41; 8.20). The risk of fetal death increased more when ARD in pregnancy was accompanied by vaginal delivery (aOR 7.06 CI 95% 4.21; 11.83), or admission to Intensive Care Unit (aOR 8.79 CI 95% 4.96; 15.58), or use of invasive mechanical ventilation (aOR 21.22 CI 95% 9.93; 45.36). CONCLUSION: Our findings can contribute to expanding the understanding of health professionals and managers about the harmful effects of SARS-CoV-2 on maternal-fetal health and alerts the need to prioritize pregnant women in preventive actions against SARS-CoV-2 and other respiratory viruses. It also suggests that pregnant women, infected with SARS-CoV-2, need to be monitored to prevent complications of ARD, including a careful assessment of the risks and benefits of early delivery to prevent fetal death.

National data linkage assessment of live births and deaths in Mexico: Estimating under-five mortality rate ratios for vulnerable newborns and trends from 2008 to 2019.

BACKGROUND: Linked datasets that enable longitudinal assessments are scarce in low and middle-income countries. OBJECTIVES: We aimed to assess the linkage of administrative databases of live births and under-five child deaths to explore mortality and trends for preterm, small (SGA) and large for gestational age (LGA) in Mexico. METHODS: We linked individual-level datasets collected by National statistics from 2008 to 2019. Linkage was performed based on agreement on birthday, sex, residential address. We used the Centre for Data and Knowledge Integration for Health software to identify the best candidate pairs based on similarity. Accuracy was assessed by calculating the area under the receiver operating characteristic curve. We evaluated completeness by comparing the number of linked records with reported deaths. We described the percentage of linked records by baseline characteristics to identify potential bias. Using the linked dataset, we calculated mortality rate ratios (RR) in neonatal, infants, and children under-five according to gestational age, birthweight, and size. RESULTS: For the period 2008-2019, a total of 24,955,172 live births and 321,165 under-five deaths were available for linkage. We excluded 1,539,046 records (6.2%) with missing or implausible values. We succesfully linked 231,765 deaths (72.2%: range 57.1% in 2009 and 84.3% in 2011). The rate of neonatal mortality was higher for preterm compared with term (RR 3.83, 95% confidence interval, [CI] 3.78, 3.88) and for SGA compared with appropriate for gestational age (AGA) (RR 1.22 95% CI, 1.19, 1.24). Births at <28 weeks had the highest mortality (RR 35.92, 95% CI, 34.97, 36.88). LGA had no additional risk vs AGA among children under five (RR 0.92, 95% CI, 0.90, 0.93). CONCLUSIONS: We demonstrated the utility of linked data to understand neonatal vulnerability and child mortality. We created a linked dataset that would be a valuable resource for future population-based research.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study.

BACKGROUND: Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron's emergence accelerating their booster program. Despite this, both countries have reported substantial recent increases in Coronavirus Disease 2019 (COVID-19) cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear. METHODS AND FINDINGS: Using a test-negative design, we analyzed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus an mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death) during the period of Omicron dominance in Brazil and Scotland compared to unvaccinated individuals. Additional analyses included stratification by age group (18 to 49, 50 to 64, ≥65). All individuals aged 18 years or older who reported acute respiratory illness symptoms and tested for SARS-CoV-2 infection between January 1, 2022, and April 23, 2022, in Brazil and Scotland were eligible for the study. At 14 to 29 days after the mRNA booster, the VE against symptomatic SARS-CoV-2 infection of ChAdOx1 plus BNT162b2 booster was 51.6%, (95% confidence interval (CI): [51.0, 52.2], p < 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], p < 0.001) in Scotland. At ≥4 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], p = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], p < 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], p < 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], p < 0.001) and 98.3% (95% CI [87.3, 99.8], p < 0.001) to 77.8% (95% CI [51.4, 89.9], p < 0.001) in Scotland for the same periods. Similar results were obtained with the primary series of BNT162b2 plus homologous booster. Potential limitations of this study were that we assumed that all cases included in the analysis were due to the Omicron variant based on the period of dominance and the limited follow-up time since the booster dose. CONCLUSIONS: We observed that mRNA boosters after a primary vaccination course with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron but substantial and more sustained protection against severe COVID-19 outcomes for at least 3 months.

Pregnancy during COVID-19: social contact patterns and vaccine coverage of pregnant women from CoMix in 19 European countries.

BACKGROUND: Evidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries. METHODS: In each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the adjusted mean number of contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap. FINDINGS: We recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18-49. Pregnant women made slightly fewer contacts (3.6, 95%CI = 3.5-3.7) than non-pregnant women (4.0, 95%CI = 3.9-4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15-20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period. COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women. INTERPRETATION: Limited social contact to avoid pathogen exposure during the COVID-19 pandemic has been a challenge to many, especially women going through pregnancy. More recognition of maternal social support desire is needed in the ongoing pandemic. As COVID-19 vaccination continues to remain an important pillar of outbreak response, strategies to promote correct information can provide reassurance and facilitate informed pregnancy vaccine decisions in this vulnerable group.

Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil.

There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14-30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3-55.7) against confirmed infection and 82.1% (95% CI: 81.4-82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1-36.2) against infection and 72.5% (95% CI: 70.9-74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0-94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1-98.1) 14-30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.

Vaccine effectiveness of CoronaVac against COVID-19 among children in Brazil during the Omicron period.

Although severe COVID-19 in children is rare, they may develop multisystem inflammatory syndrome, long-COVID and downstream effects of COVID-19, including social isolation and disruption of education. Data on the effectiveness of the CoronaVac vaccine is scarce during the Omicron period. In Brazil, children between 6 to 11 years are eligible to receive the CoronaVac vaccine. We conducted a test-negative design to estimate vaccine effectiveness using 197,958 tests from January 21, 2022, to April 15, 2022, during the Omicron dominant period in Brazil among children aged 6 to 11 years. The estimated vaccine effectiveness for symptomatic infection was 39.8% (95% CI 33.7-45.4) at ≥14 days post-second dose. For hospital admission vaccine effectiveness was 59.2% (95% CI 11.3-84.5) at ≥14 days. Two doses of CoronaVac in children during the Omicron period showed low levels of protection against symptomatic infection, and modest levels against severe illness.

Effectiveness of CoronaVac, ChAdOx1 nCoV-19, BNT162b2, and Ad26.COV2.S among individuals with previous SARS-CoV-2 infection in Brazil: a test-negative, case-control study.

BACKGROUND: COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. METHODS: Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. FINDINGS: Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1-42·6) for CoronaVac, 56·0% (51·4-60·2) for ChAdOx1 nCoV-19, 44·0% (31·5-54·2) for Ad26.COV2.S, and 64·8% (54·9-72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3-85·8) for CoronaVac, 89·9% (83·5-93·8) for ChAdOx1 nCoV-19, 57·7% (-2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3-97·7) for BNT162b2. INTERPRETATION: All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. FUNDING: Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.

Vaccine effectiveness of two-dose BNT162b2 against symptomatic and severe COVID-19 among adolescents in Brazil and Scotland over time: a test-negative case-control study.

BACKGROUND: Little is known about vaccine effectiveness over time among adolescents, especially against the SARS-CoV-2 omicron (B.1.1.529) variant. This study assessed the associations between time since two-dose vaccination with BNT162b2 and the occurrence of symptomatic SARS-CoV-2 infection and severe COVID-19 among adolescents in Brazil and Scotland. METHODS: We did test-negative, case-control studies in adolescents aged 12-17 years with COVID-19-related symptoms in Brazil and Scotland. We linked records of SARS-CoV-2 RT-PCR and antigen tests to national vaccination and clinical records. We excluded tests from individuals who did not have symptoms, were vaccinated before the start of the national vaccination programme, received vaccines other than BNT162b2 or a SARS-CoV-2 booster dose of any kind, or had an interval between their first and second dose of fewer than 21 days. Additionally, we excluded negative SARS-CoV-2 tests recorded within 14 days of a previous negative test, negative tests recorded within 7 days after a positive test, any test done within 90 days after a positive test, and tests with missing sex and location information. Cases (SARS-CoV-2 test-positive adolescents) and controls (test-negative adolescents) were drawn from a sample of individuals in whom tests were collected within 10 days of symptom onset. We estimated the adjusted odds ratio and vaccine effectiveness against symptomatic COVID-19 for both countries and against severe COVID-19 (hospitalisation or death) for Brazil across fortnightly periods. FINDINGS: We analysed 503 776 tests from 2 948 538 adolescents in Brazil between Sept 2, 2021, and April 19, 2022, and 127 168 tests from 404 673 adolescents in Scotland between Aug 6, 2021, and April 19, 2022. Vaccine effectiveness peaked at 14-27 days after the second dose in both countries during both waves, and was significantly lower against symptomatic infection during the omicron-dominant period in Brazil (64·7% [95% CI 63·0-66·3]) and in Scotland (82·6% [80·6-84·5]), than it was in the delta-dominant period (80·7% [95% CI 77·8-83·3] in Brazil and 92·8% [85·7-96·4] in Scotland). Vaccine efficacy started to decline from 27 days after the second dose for both countries, reducing to 5·9% (95% CI 2·2-9·4) in Brazil and 50·6% (42·7-57·4) in Scotland at 98 days or more during the omicron-dominant period. In Brazil, protection against severe disease remained above 80% from 28 days after the second dose and was 82·7% (95% CI 68·8-90·4) at 98 days or more after receiving the second dose. INTERPRETATION: We found waning vaccine protection of BNT162b2 against symptomatic COVID-19 infection among adolescents in Brazil and Scotland from 27 days after the second dose. However, protection against severe COVID-19 outcomes remained high at 98 days or more after the second dose in the omicron-dominant period. Booster doses for adolescents need to be considered. FUNDING: UK Research and Innovation (Medical Research Council), Scottish Government, Health Data Research UK BREATHE Hub, Fiocruz, Fazer o Bem Faz Bem programme, Brazilian National Research Council, and Wellcome Trust. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Duration of protection of CoronaVac plus heterologous BNT162b2 booster in the Omicron period in Brazil.

To date, no information has been published on the effectiveness of inactivated whole-virus COVID-19 vaccines plus heterologous booster against symptomatic infection and severe outcomes (hospitalization or death) during the dominance of the SARS-CoV-2 Omicron variant period. We evaluated the vaccine effectiveness (VE) of CoronaVac plus BNT162b2 booster during the period of dominance of the Omicron variant in Brazil (January to April 2022). Using a test-negative design, we analysed data for 2,471,576 individuals tested during the Omicron variant's dominant period using a nationally linked database from Brazil. Compared to unvaccinated, vaccinees maintained protection against severe outcomes, with an estimated VE of 84.1% (95% CI:83.2-84.9) at more than 120 days after BNT162b2 booster. Furthermore, while we detected a high level of protection against severe outcomes for individuals up to 79 years old, waning was observed for individuals aged ≥80 years, with VE decreasing from 81.3% (95% CI:77.9-84.2) at 31-60 days to 72.9% (95% CI:70.6-75.1) at 120 days or more after the booster dose. However, no significant protection against symptomatic infection was observed at this time period. In conclusion, except for individuals aged ≥80 years, CoronaVac plus a BNT162b2 booster dose offered high and durable protection against severe outcomes due to Omicron.

Combined association of obesity and other cardiometabolic diseases with severe COVID-19 outcomes: a nationwide cross-sectional study of 21 773 Brazilian adult and elderly inpatients

ObjectivesTo investigate the combined association of obesity, diabetes mellitus (DM) and cardiovascular disease (CVD) with severe COVID-19 outcomes in adult and elderly inpatients.DesignCross-sectional study based on registry data from Brazil’s influenza surveillance system.SettingPublic and private hospitals across Brazil.ParticipantsEligible population included 21 942 inpatients aged ≥20 years with positive reverse transcription-PCR test for SARS-CoV-2 until 9 June 2020.Main outcome measuresSevere COVID-19 outcomes were non-invasive and invasive mechanical ventilation use, intensive care unit (ICU) admission and death. Multivariate analyses were conducted separately for adults (20–59 years) and elders (≥60 years) to test the combined association of obesity (without and with DM and/or CVD) and degrees of obesity with each outcome.ResultsA sample of 8848 adults and 12 925 elders were included. Among adults, obesity with DM and/or CVD showed higher prevalence of invasive (prevalence ratio 3.76, 95% CI 2.82 to 5.01) and non-invasive mechanical ventilation use (2.06, 1.58 to 2.69), ICU admission (1.60, 1.40 to 1.83) and death (1.79, 1.45 to 2.21) compared with the group without obesity, DM and CVD. In elders, obesity alone (without DM and CVD) had the highest prevalence of ICU admission (1.40, 1.07 to 1.82) and death (1.67, 1.00 to 2.80). In both age groups, obesity alone and combined with DM and/or CVD showed higher prevalence in all outcomes than DM and/or CVD. A dose–response association was observed between obesity and death in adults: class I 1.32 (1.05 to 1.66), class II 1.41 (1.06 to 1.87) and class III 1.77 (1.35 to 2.33).ConclusionsThe combined association of obesity, diabetes and/or CVD with severe COVID-19 outcomes may be stronger in adults than in elders. Obesity alone and combined with DM and/or CVD had more impact on the risk of COVID-19 severity than DM and/or CVD in both age groups. The study also supports an independent relationship of obesity with severe outcomes, including a dose–response association between degrees of obesity and death in adults.

Mortality from Congenital Zika Syndrome - Nationwide Cohort Study in Brazil.

BACKGROUND: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited. METHODS: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age. RESULTS: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome. CONCLUSIONS: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.).

CoronaVac vaccine is effective in preventing symptomatic and severe COVID-19 in pregnant women in Brazil: a test-negative case-control study.

BACKGROUND: More doses of CoronaVac have been administered worldwide than any other COVID-19 vaccine. However, the effectiveness of COVID-19 inactivated vaccines in pregnant women is still unknown. We estimated the vaccine effectiveness (VE) of CoronaVac against symptomatic and severe COVID-19 in pregnant women in Brazil. METHODS: We conducted a test-negative design study in all pregnant women aged 18-49 years with COVID-19-related symptoms in Brazil from March 15, 2021, to October 03, 2021, linking records of negative and positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests to national vaccination records. We also linked records of test-positive cases with notifications of severe, hospitalised or fatal COVID-19. Using logistic regression, we estimated the adjusted odds ratio and VE against symptomatic COVID-19 and against severe COVID-19 by comparing vaccine status in test-negative subjects to test-positive symptomatic cases and severe cases. RESULTS: Of the 19,838 tested pregnant women, 7424 (37.4%) tested positive for COVID-19 and 588 (7.9%) had severe disease. Only 83% of pregnant women who received the first dose of CoronaVac completed the vaccination scheme. A single dose of the CoronaVac vaccine was not effective at preventing symptomatic COVID-19. The effectiveness of two doses of CoronaVac was 41% (95% CI 27.1-52.2) against symptomatic COVID-19 and 85% (95% CI 59.5-94.8) against severe COVID-19. CONCLUSIONS: A complete regimen of CoronaVac in pregnant women was effective in preventing symptomatic COVID-19 and highly effective against severe illness in a setting that combined high disease burden and marked COVID-19-related maternal deaths.

Impact of COVID-19 pandemic on time series of maternal mortality ratio in Bahia, Brazil: analysis of period 2011-2020.

BACKGROUND: Most studies on the effects of SARS-CoV-2 infection have been conducted with adults and non-pregnant women. Thus, its impacts on maternal health are not yet fully established. This study aimed to verify the relationship between the maternal mortality ratio and the incidence of COVID-19 in the State of Bahia, Brazil, 2020. METHODS: This time-series study used publicly available information in Brazil, to obtain data on maternal deaths and live births in Bahia, State, from January 1, 2011, to December 31, 2020. The time trend of Maternal Mortality Ratio (MMR) was analysed through polynomial regression, of order 6. Expected MMR, monthly (Jan-Dec) and annual values for 2020, were predicted by the additive Holt-Winters exponential smoothing algorithm, with 95% confidence interval, based on the time series of the MMR from 2011 to 2019, and the accuracy of the forecasts for 2020 was assessed by checking the smoothing coefficients and the mean errors. According to the statistical forecast, the MMR values ​​recorded in the year 2020 were compared to those expected. RESULTS: In 2020, the annual MMR in Bahia, Brazil, was 78.23/100,000 live births, 59.46% higher than the expected ratio (49.06 [95% CI 38.70-59.90]). The increase in maternal mortality ratio relative to expected values was observed throughout the 2020 months; however, only after May, when the COVID-19 epidemic rose sharply, it exceeded the upper limit of the 95% CI of the monthly prediction. Of the 144 registered maternal deaths in 2020, 19 (13.19%) had COVID-19 mentioned as the cause of death. CONCLUSIONS: Our study revealed the increase in maternal mortality, and its temporal relationship with the incidence of COVID-19, in Bahia, Brazil, in 2020. The COVID-19 pandemic may be directly and indirectly related to this increase, which needs to be investigated. An urgent public health action is needed to prevent and reduce maternal deaths during this pandemic, in Brazil.

Long-term impact of a conditional cash transfer programme on maternal mortality: a nationwide analysis of Brazilian longitudinal data.

BACKGROUND: Reducing poverty and improving access to health care are two of the most effective actions to decrease maternal mortality, and conditional cash transfer (CCT) programmes act on both. The aim of this study was to evaluate the effects of one of the world's largest CCT (the Brazilian Bolsa Familia Programme (BFP)) on maternal mortality during a period of 11 years. METHODS: The study had an ecological longitudinal design and used all 2548 Brazilian municipalities with vital statistics of adequate quality during 2004-2014. BFP municipal coverage was classified into four levels, from low to consolidated, and its duration effects were measured using the average municipal coverage of previous years. We used negative binomial multivariable regression models with fixed-effects specifications, adjusted for all relevant demographic, socioeconomic, and healthcare variables. RESULTS: BFP was significantly associated with reductions of maternal mortality proportionally to its levels of coverage and years of implementation, with a rate ratio (RR) reaching 0.88 (95%CI 0.81-0.95), 0.84 (0.75-0.96) and 0.83 (0.71-0.99) for intermediate, high and consolidated BFP coverage over the previous 11 years. The BFP duration effect was stronger among young mothers (RR 0.77; 95%CI 0.67-0.96). BFP was also associated with reductions in the proportion of pregnant women with no prenatal visits (RR 0.73; 95%CI 0.69-0.77), reductions in hospital case-fatality rate for delivery (RR 0.78; 95%CI 0.66-0.94) and increases in the proportion of deliveries in hospital (RR 1.05; 95%CI 1.04-1.07). CONCLUSION: Our findings show that a consolidated and durable CCT coverage could decrease maternal mortality, and these long-term effects are stronger among poor mothers exposed to CCT during their childhood and adolescence, suggesting a CCT inter-generational effect. Sustained CCT coverage could reduce health inequalities and contribute to the achievement of the Sustainable Development Goal 3.1, and should be preserved during the current global economic crisis due to the COVID-19 pandemic.

The need for fast-track, high-quality and low-cost studies about the role of the BCG vaccine in the fight against COVID-19.

Bacillus Calmette-Guérin (BCG) vaccination is routine and near-universal in many low- and middle-income countries (LMIC). It has been suggested that BCG can have a protective effect on COVID-19 morbidity and mortality. This commentary discusses the limitations of the evidence around BCG and COVID-19. We argue that higher-quality evidence is necessary to understand the protective effect of the BCG vaccine from existing, secondary data, while we await results from clinical trials currently conducted in different settings.