The effectiveness of COVID-19 vaccines against severe cases and deaths in Brazil from 2021 to 2022: a registry-based study

Background Brazil started the COVID-19 mass vaccination in January 2021 with CoronaVac and ChAdOx1, followed by BNT162b2 and Ad26.COV2.S vaccines. By the end of 2021, more than 317 million vaccine doses were administered in the adult population. This study aimed at estimating the effectiveness of the primary series of COVID-19 vaccination and booster shots in protecting against severe cases and deaths in Brazil during the first year of vaccination. Methods A cohort dataset of over 158 million vaccination and severe cases records linked from official national registries was analyzed via a mixed-effects Poisson model, adjusted for age, state of residence, time after immunization, and calendar time to estimate the absolute vaccine effectiveness of the primary series of vaccination and the relative effectiveness of the booster. The method permitted analysis of effectiveness against hospitalizations and deaths, including in the periods of variant dominance. Findings Vaccine effectiveness against severe cases and deaths remained over 25% and 50%, respectively, after 19 weeks from primary vaccination of BNT162b2, ChAdOx1, or CoronaVac vaccines. The boosters conferred greater protection than the primary series of vaccination, with heterologous boosters providing marginally greater protection than homologous. The effectiveness against hospitalization during the Omicron dominance in the 60+ years old population started at 61.7% (95% CI, 26.1–86.2) for ChAdOx1, 95.6% (95% CI, 82.4–99.9) for CoronaVac, and 72.3% (95% CI, 51.4–87.4) for the BNT162b2 vaccine. Interpretation This study provides real-world evidence of the effectiveness of COVID-19 vaccination in Brazil, including during the Omicron wave, demonstrating protection even after waning effectiveness. Comparisons of the effectiveness among different vaccines require caution due to potential bias effects related to age groups, periods in the pandemic, and eventual behavioural changes. Funding 10.13039/501100006507Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (10.13039/501100003593CNPq), 10.13039/501100004586Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), 10.13039/100011893Pan American Health Organization (PAHO), Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde do Brasil (DECIT/SCTIE/MS).

The effectiveness of COVID-19 vaccines against severe cases and deaths in Brazil from 2021 to 2022: a registry-based study.

Background: Brazil started the COVID-19 mass vaccination in January 2021 with CoronaVac and ChAdOx1, followed by BNT162b2 and Ad26.COV2.S vaccines. By the end of 2021, more than 317 million vaccine doses were administered in the adult population. This study aimed at estimating the effectiveness of the primary series of COVID-19 vaccination and booster shots in protecting against severe cases and deaths in Brazil during the first year of vaccination. Methods: A cohort dataset of over 158 million vaccination and severe cases records linked from official national registries was analyzed via a mixed-effects Poisson model, adjusted for age, state of residence, time after immunization, and calendar time to estimate the absolute vaccine effectiveness of the primary series of vaccination and the relative effectiveness of the booster. The method permitted analysis of effectiveness against hospitalizations and deaths, including in the periods of variant dominance. Findings: Vaccine effectiveness against severe cases and deaths remained over 25% and 50%, respectively, after 19 weeks from primary vaccination of BNT162b2, ChAdOx1, or CoronaVac vaccines. The boosters conferred greater protection than the primary series of vaccination, with heterologous boosters providing marginally greater protection than homologous. The effectiveness against hospitalization during the Omicron dominance in the 60+ years old population started at 61.7% (95% CI, 26.1-86.2) for ChAdOx1, 95.6% (95% CI, 82.4-99.9) for CoronaVac, and 72.3% (95% CI, 51.4-87.4) for the BNT162b2 vaccine. Interpretation: This study provides real-world evidence of the effectiveness of COVID-19 vaccination in Brazil, including during the Omicron wave, demonstrating protection even after waning effectiveness. Comparisons of the effectiveness among different vaccines require caution due to potential bias effects related to age groups, periods in the pandemic, and eventual behavioural changes. Funding: Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Pan American Health Organization (PAHO), Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde do Brasil (DECIT/SCTIE/MS).

Adverse Events Related to COVID-19 Vaccines Reported in Pregnant Women in Brazil.

Regulations for the vaccination of pregnant women in Brazil occurred in March 2021. Despite the absence of robust data in the literature on the coronavirus disease 2019 (COVID-19) vaccinations in pregnant women, it is understood that the benefit-risk ratio tends to be favorable when considering the pandemic and the high burden of the disease. However, it is still important to monitor for Events Supposedly Attributable to Vaccination or Immunization (ESAVI) and to draw safety profiles of the different platforms used in pregnant and postpartum women. The present study aims to describe the main characteristics of ESAVIs related to COVID-19 vaccines occurring in pregnant women in the first months of the vaccination campaign in Brazil. During the evaluation period, 1,674 notifications of ESAVIs in pregnant women were recorded, and 582 notifications were included for the analysis. Of the 582 ESAVIs identified, 481 (82%) were classified as non-serious adverse events and 101 (17%) as serious adverse events. Ten deaths were identified, including one death which was considered to be causally related to the vaccine. The other nine maternal deaths had causality C, that is, without causal relationship with the vaccine, and most were due to complications inherent to pregnancy, such as pregnancy-specific hypertensive disorder (PSHD) in 4 cases and 3 due to COVID-19. Despite some limitations in our study, we believe it brings new insights into COVID-19 vaccines in this group and will add to the available evidence.

As determinações vacinação nas gestantes foram estabelecidas em março de 2021, no Brasil. Apesar da ausência de dados robustos na literatura da vacinação contra coronavirus disease 2019 (COVID-19) nesse grupo, entende-se que a relação de benefício versus risco tende a ser favorável considerando a situação pandêmica e a elevada carga de doença, tendo justificado o uso dessas vacinas em ampla escala nas gestantes de todo o mundo. Entretanto, o monitoramento dos eventos adversos pós vacinação (EAPVs) torna-se ainda mais importante para traçar um perfil de segurança das diferentes plataformas nas gestantes e puérperas. O presente estudo tem como objetivo descrever as principais características dos EAPVs contra COVID-19 ocorridos nas gestantes nos primeiros meses de campanha da vacinação no Brasil. Foram identificadas 1.674 notificações em gestantes, com a inclusão de 582 EAPVs analisados. Dos 582 EAPVs identificados, 481 (82%) foram classificados como eventos adversos não-graves e 101 (17%) como eventos adversos graves, sendo 10 (9,9%) destes referentes aos óbitos. Apenas um caso de óbito materno teve relação causal com a vacinação comprovada (causalidade A1), e foi secundário à síndrome trombocitopênica trombótica (TTS) após a vacina AstraZeneca/Fiocruz. Os outros nove óbitos maternos tiveram causalidade C, ou seja, sem relação causal com a vacina, e a maioria por complicações inerentes à gravidez, como a doença hipertensiva específica da gestação (DHEG) e COVID-19. Apesar de algumas limitações em nosso estudo, acreditamos que ele traz dados importantes sobre as vacinas COVID-19 neste grupo aumentando as evidências disponíveis.

Association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil: a prospective cohort study.

Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.

Y380Q novel mutation in receptor-binding domain of SARS-CoV-2 spike protein together with C379W interfere in the neutralizing antibodies interaction.

We aimed to describe the SARS-CoV-2 lineages circulating early pandemic among samples with S gene dropout and characterize the receptor-binding domain (RBD) of viral spike protein. Adults and children older than 2 months with signs and symptoms of COVID-19 were prospectively enrolled from May to October in Porto Alegre, Brazil. All participants performed RT-PCR assay, and samples with S gene dropout and cycle threshold < 30 were submitted to high-throughput sequencing (HTS). 484 out of 1,557 participants tested positive for SARS-CoV-2. The S gene dropout was detected in 7.4% (36/484) and a peak was observed in August. The B.1.1.28, B.1.91 and B.1.1.33 lineages were circulating in early pandemic. The RBD novel mutation (Y380Q) was found in one sample occurring simultaneously with C379W and V395A, and the B.1.91 lineage in the spike protein. The Y380Q and C379W may interfere with the binding of neutralizing antibodies (CR3022, EY6A, H014, S304).

Diagnostic accuracy of a SARS-CoV-2 rapid test and optimal time for seropositivity according to the onset of symptoms.

Point-of-care serological tests for SARS-CoV-2 have been used for COVID-19 diagnosis. However, their accuracy over time regarding the onset of symptoms is not fully understood. We aimed to assess the accuracy of a point-of-care lateral flow immunoassay (LFI). Subjects, aged over 18 years, presenting clinical symptoms suggestive of acute SARS-CoV-2 infection were tested once by both nasopharyngeal and oropharyngeal RT-PCR and LFI. The accuracy of LFI was assessed in periodic intervals of three days in relation to the onset of symptoms. The optimal cut-off point was defined as the number of days required to achieve the best sensitivity and specificity. This cut-off point was also used to compare LFI accuracy according to participants' status: outpatient or hospitalized. In total, 959 patients were included, 379 (39.52%) tested positive for SARS-CoV-2 with RT-PCR, and 272 (28.36%) tested positive with LFI. LFI best performance was achieved after 10 days of the onset of symptoms, with sensitivity and specificity of 84.9% (95%CI: 79.8-89.1) and 94.4% (95%CI: 91.0-96.8), respectively. Although the specificity was similar (94.6% vs. 88.9%, p = 0.051), the sensitivity was higher in hospitalized patients than in outpatients (91.7% vs. 82.1%, p = 0.032) after 10 days of the onset of symptoms. Best sensitivity of point-of-care LFI was found 10 days after the onset of symptoms which may limit its use in acute care. Specificity remained high regardless of the number of days since the onset of symptoms.

Identification of priority groups for COVID-19 vaccination in Brazil. / Identificação de grupos prioritários para a vacinação contra COVID-19 no Brasil.

In a context of community transmission and shortage of vaccines, COVID-19 vaccination should focus on directly reducing the morbidity and mortality caused by the disease. It was thus essential to define priority groups for vaccination by the Brazilian National Immunization Program (PNI in Portuguese), based on the risk of hospitalization and death from the disease. We calculated overrisk according to sex, age group, and comorbidities using hospitalization and death records from severe acute respiratory illness with confirmation of COVID-19 (SARI-COVID) in all of Brazil in the first 6 months of the epidemic. Higher overrisk was associated with male sex (hospitalization = 1.1 and death = 1.2), age over 45 years for hospitalization (OvRag ranging from 1.1 to 8.5), and age over 55 year for death (OvRag ranging from 1.5 to 18.3). In the groups with comorbidities, chronic kidney disease, diabetes mellitus, cardiovascular disease, and chronic lung disease were associated with overrisk, while there was no such evidence for asthma. Chronic kidney disease or diabetes and age over 60 showed an even stronger association, reaching overrisk of death 14 and 10 times greater than in the general population, respectively. For all the comorbidities, there was higher overrisk at older ages, with a downward gradient in the oldest age groups. This pattern was reversed when examining overrisk in the general population, for both hospitalization and death. The current study provided evidence of overrisk of hospitalization and death from SARI-COVID, assisting the definition of priority groups for COVID-19 vaccination.

Em um contexto de transmissão comunitária e escassez de vacinas, a vacinação contra a COVID-19 deve focar na redução direta da morbidade e da mortalidade causadas pela doença. Portanto, é fundamental a definição de grupos prioritários para a vacinação pelo Programa Nacional de Imunizações (PNI), baseada no risco de hospitalização e óbito pela doença. Para tal, calculamos o sobrerrisco por sexo, faixa etária e comorbidades por meio dos registros de hospitalização e óbito por síndrome respiratória aguda grave com confirmação de COVID-19 (SRAG-COVID) em todo o Brasil nos primeiros seis meses de epidemia. Apresentaram maior sobrerrisco pessoas do sexo masculino (hospitalização = 1,1 e óbito = 1,2), pessoas acima de 45 anos para hospitalização (SRfe variando de 1,1 a 8,5) e pessoas acima de 55 anos para óbitos (SRfe variando de 1,5 a 18,3). Nos grupos de comorbidades, doença renal crônica, diabetes mellitus, doença cardiovascular e pneumopatia crônica conferiram sobrerrisco, enquanto para asma não houve evidência. Ter doença renal crônica ou diabetes mellitus e 60 anos ou mais mostrou-se um fator ainda mais forte, alcançando sobrerrisco de óbito 14 e 10 vezes maior do que na população geral, respectivamente. Para todas as comorbidades, houve um sobrerrisco mais alto em idades maiores, com um gradiente de diminuição em faixas mais altas. Esse padrão se inverteu quando consideramos o sobrerrisco em relação à população geral, tanto para hospitalização quanto para óbito. O presente estudo forneceu evidências a respeito do sobrerrisco de hospitalização e óbito por SRAG-COVID, auxiliando na definição de grupos prioritários para a vacinação contra a COVID-19.

En un contexto de transmisión comunitaria y escasez de vacunas, la vacunación contra la COVID-19 debe enfocarse en la reducción directa de la morbilidad y de la mortalidad causadas por la enfermedad. Por lo tanto, es fundamental la definición de grupos prioritarios para la vacunación por el Programa Nacional de Inmunizaciones (PNI), basada en el riesgo de hospitalización y óbito por la enfermedad. Para tal fin, calculamos el sobrerriesgo por sexo, franja de edad y comorbilidades mediante los registros de hospitalización y óbito por síndrome respiratorio agudo grave con confirmación de COVID-19 (SRAG-COVID) en todo Brasil, durante los primeros seis meses de epidemia. Presentaron mayor sobrerriesgo personas del sexo masculino (hospitalización = 1,1 y óbito = 1,2), personas por encima de 45 años para hospitalización (SRfe variando de 1,1 a 8,5) y personas por encima de 55 años para óbitos (SRfe variando de 1,5 a 18,3). En los grupos de comorbilidades, enfermedad renal crónica, diabetes mellitus, enfermedad cardiovascular y neumopatía crónica ofrecieron sobrerriesgo, mientras que para el asma no hubo evidencia. Sufrir una enfermedad renal crónica o diabetes mellitus y tener 60 años o más mostró un factor todavía más fuerte, alcanzando sobrerriesgo de enfermedad 14 y 10 veces mayor que en la población general, respectivamente. Para todas las comorbilidades, hubo un sobrerriesgo más alto en edades mayores, con un gradiente de disminución en franjas más altas. Este patrón se invirtió cuando consideramos el sobrerriesgo en relación con la población general, tanto para hospitalización como para óbito. El presente estudio proporcionó evidencias respecto al sobrerriesgo de hospitalización y óbito por SRAG-COVID, ayudando en la definición de grupos prioritarios para la vacunación contra la COVID-19.

Children Have Similar Reverse Transcription Polymerase Chain Reaction Cycle Threshold for Severe Acute Respiratory Syndrome Coronavirus 2 in Comparison With Adults.

BACKGROUND: The viral dynamics and the role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not completely understood. Our aim was to evaluate reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) values among children with confirmed SARS-CoV-2 compared with that of adult subjects. METHODS: Patients (from 2 months to ≤18 years of age and adults) with signs and symptoms of acute SARS-CoV-2 infection for less than 7 days were prospectively enrolled in the study from May to November 2020. All participants performed RT-PCR assay for SARS-CoV-2 detection; Ct values of ORF1ab, N and S gene targets and the average of all the 3 probes were used as surrogates of viral load. RESULTS: There were 21 infants (2 months to <2 years), 40 children (≥2 to <12 years), 22 adolescents (≥12 to <18 years) and 293 adults of 376 participants with confirmed SARS-CoV-2 infections. RT-PCR Ct values from all participants less than 18 years of age, as well as from all childhood subgroups, were not significantly different from adults, comparing ORF1ab, N, S and all the gene targets together (P = 0.453). CONCLUSIONS: Ct values for children were comparable with that of adults. Although viral load is not the only determinant of SARS-CoV-2 transmission, children may play a role in the spread of coronavirus disease 2019 in the community.

Low performance of a SARS-CoV-2 point-of-care lateral flow immunoassay in symptomatic children during the pandemic.

OBJECTIVE: to evaluate the accuracy of an antibody point-of-care lateral flow immunoassay (LFI - Wondfo Biotech Co., Guangzhou, China) in a pediatric population. METHODS: children and adolescents (2 months to 18 years) with signs and symptoms suggestive of acute SARS-CoV-2 infection were prospectively investigated with nasopharyngeal RT-PCR and LFI at the emergency room. RT-PCR was performed at baseline, and LFI at the same time or scheduled for those with less than 7 days of the clinical picture. Overall accuracy, sensitivity and specificity were assessed, as well as according to the onset of symptoms (7-13 or ≥14 days) at the time of the LFI test. RESULTS: In 175 children included, RT-PCR and LFI were positive in 51 (29.14%) and 36 (20.57%), respectively. The overall sensitivity, specificity, positive and negative predictive value was 70.6% (95%CI 56.2-82.5), 96.8% (95%CI 91.9-99.1), 90.0% (95%CI 77.2-96.0), and 88.9% (95%CI 83.9-92.5), respectively. At 7-13 and ≥14 days after the onset of symptoms, sensitivity was 60.0% (95%CI 26.2-87.8) and 73.2% (95%CI 57.1-85.8) and specificity was 97.9% (95%CI 88.7-99.9) and 96.1% (95%CI 89.0-99.2), respectively. CONCLUSION: Despite its high specificity, in the present study the sensitivity of LFI in children was lower (around 70%) than most reports in adults. Although a positive result is informative, a negative LFI test cannot rule out COVID-19 in children.

Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.