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Since its initial detection in Brazil in February 2020, SARS-CoV-2 and the associated COVID-19 pandemic have continued to devastate Latin America. Specific comorbidities, as well as sociodemographic and lifestyle factors that may be more prevalent in underserved areas, have been identified as risk factors for COVID-19 infection or associated adverse outcomes. Dynamics of infections and deaths in Latin America have varied by country and temporally, as has SARS-CoV-2 variant prevalence; however, more recently, the Delta and subsequent Omicron variants have become ubiquitous. Successful pandemic responses have involved robust infection mitigation measures, testing, and smart deployment of healthcare resourcing. While in some Latin American countries up to 90% of the population is fully vaccinated (i.e., 2 doses) against COVID-19, other countries have failed to reach the World Health Organization's 70% target. Continued focus on comprehensive surveillance, strategies to maximize vaccine availability and uptake, and mitigation of collateral damage on other aspects of public health and social services are critical for managing the COVID-19 pandemic. This review summarizes the COVID-19 experience in Latin America, including epidemiology and vaccination. Key learnings and future considerations for the ongoing pandemic response are also discussed. [ABSTRACT FROM AUTHOR]

Background: AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated., Methods: In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed., Findings: Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2., Interpretation: Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants., Funding: AstraZeneca., Competing Interests: Declaration of interests SACC declares participation in the clinical development, with University of Oxford, of the vaccines described in this Article, membership on CureVac and Clover advisory boards, and institutional research grants from AstraZeneca. BJ is an employee of Cytel and is currently on assignment to AstraZeneca. QEB declares institutional funding, the provision of study materials, or both from the Wits Health Consortium, the Bill & Melinda Gates Foundation, the South African Medical Research Council, and AstraZeneca, as well as research grants or contracts from Regeneron, Novo Nordisk, Avillion, GlaxoSmithKline, Novavax, Sinovac, Johnson & Johnson, and Pfizer pharmaceuticals. PKA declares institutional grants to support the conduct of the study from AstraZeneca and the UK Vaccine Taskforce via the UK National Institute for Health Research (NIHR). HB is an employee of Bogier consulting and is currently on assignment to AstraZeneca. EJK is an employee of Sanofi. SM is an employee of Exploristics and is currently on assignment to AstraZeneca. EPM declares no competing interests. TL declares consulting fees from Vaccitech on an unrelated project, an honorarium from Seqirus on an unrelated project, an institutional grant from the UK Vaccine Taskforce via the NIHR, work-related investments, and is a named inventor on a patent application for a vaccine against SARS-CoV-2. JJL declares no competing interests. MNR declares institutional support for the study from AstraZeneca. AJP is Chair of the UK Department of Health and Social Care’s Joint Committee on Vaccination and Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee. AJP also declares membership of the WHO’s Strategic Advisory Group of Experts on Immunization until January, 2022; provision of advice to Shionogi on COVID-19; and funding from the NIHR, AstraZeneca, the Bill & Melinda Gates Foundation, Wellcome, the UK Research and Innovation Medical Research Council, the Serum Institute of India, and the Coalition for Epidemic Preparedness Innovations. University of Oxford has entered a partnership with AstraZeneca for the development of COVID-19 vaccines; TL, MNR, SB, PKA, and AJP are contributors to the intellectual property licensed by Oxford University Innovation to AstraZeneca. AA, TA, EJK, MK, UO, SS, KS, AS, TV, and JAG are, or were, employees of and may hold (or have held) stock or stock options in AstraZeneca. MSMdOP declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

ChAdOx1-S is a viral vector vaccine developed by AstraZeneca. We aimed to assess the effectiveness of 1 and 2 doses of the ChAdOx1-S vaccine in reducing COVID-19-related in-hospital mortality in individuals with schizophrenia. This is a retrospective cohort study using a nationwide hospital database in Brazil. Individuals diagnosed with COVID-19 and schizophrenia were included in the study. The exposures were 0, 1, and 2 doses of ChAdOx1-S. The outcome of mortality was measured in hazard ratios (HR), calculated using multivariable Cox regression models. The study included 1,929 positive cases of COVID-19 in schizophrenia patients. After adjusting for age, socioeconomic factors, and comorbidities, we observed a significant 55% decrease in the hazard of mortality in the 2-dose vaccination group (HR 0.45, 95% CI: 0.310-0.652) compared to the unvaccinated. Surprisingly, our results did not show any significant reduction in the hazard of mortality in the 1 dose vaccination group (HR 1.278, 95% CI: 0.910-1.795). The effectiveness of two doses of ChAdOx1-S in individuals with schizophrenia aligns with findings from studies on the general population. That one dose was insignificant. Overall, these findings are important for informing public health decisions - prioritizing individuals with schizophrenia for vaccinations and managing acceptance of vaccines.

We investigated the impact of the fourth dose with ChAdOx1 nCoV-19 (AstraZeneca) in the humoral immune response to SARS-CoV-2 during a 9-month follow-up period in which Omicron was the predominant variant in Brazil. IgG for the SARS-CoV-2 spike protein (S) and nucleocapsid (N) proteins were analyzed in samples collected before and after the fourth dose. All participants were tested monthly for SARS-CoV-2 infection by RT-qPCR. The antibody response induced by the fourth dose of the coronavirus disease 2019 vaccine was evaluated and compared with the response induced by the second and third doses. The additional antibody response to the viral S protein after the fourth dose was smaller than those after the third vaccine dose. In contrast, an increase in the N IgG levels could be observed after the fourth dose compared to other vaccine doses. In the comparison of the antibody response before and after the fourth dose, an increase in both S-and-N IgG was noted, mainly in the positive qPCR group. We did not observe a significant decline in IgG levels after the fourth dose, as observed after the second and third doses, therefore, a sustained humoral response to both S and N proteins seems to be achieved., (© 2023 Wiley Periodicals LLC.)

In this phase 4 study we assessed boosting with fractional doses of heterologous COVID-19 vaccines in Brazilian adults primed with two doses of CoronaVac (Sinovac/Butantan, São Paulo, Brazil) at least 4 months previously. Participants received either full-dose of ChAdOx1-S (Group 1, n  = 232), a half dose of ChAdOx1-S (Group 2, n  = 236), or a half dose of BNT162b2 (Group 3, n  = 234). The primary objective was to show 80% seroresponse rates (SRR) 28 d after vaccination measured as IgG antibodies against a prototype SARS-CoV-2 spike-protein. Safety was assessed as solicited and unsolicited adverse events. At baseline all participants were seropositive, with high IgG titers overall. SRR at Day 28 were 34.3%, 27.1% and 71.2%, respectively, not meeting the primary objective of 80%, despite robust immune responses in all three groups with geometric mean-fold rise (GMFR) in IgG titers of 3.39, 2.99 and 7.42, respectively. IgG immune responses with similar GMFR were also observed against SARS-CoV-2 variants, Alpha, Beta, Delta, Gamma and D614G. In subsets ( n  = 35) of participants GMFR of neutralizing immune responses against live prototype SARS-CoV-2 virus and Omicron BA.2 were similar to the IgG responses as were pseudo-neutralizing responses against SARS-CoV-2 prototype and Omicron BA.4/5 variants. All vaccinations were well tolerated with no vaccine-related serious adverse events and mainly transient mild-to-moderate local and systemic reactogenicity. Heterologous boosting with full or half doses of ChAdOx1-S or a half dose of BNT162b2 was safe and immunogenic in CoronaVac-primed adults, but seroresponse rates were limited by high baseline immunity.

Several vaccines have been produced in 2 years of the COVID-19 pandemic to control the infection outbreak. This study demonstrated the success of vaccination in controlling COVID-19 cases and deaths in a small city (41 424 people) with a low population density in Brazil. This study was based on a 1-year dataset since the application of the first dose in January 2021. The results show a reduction in positive cases and deaths as the vaccination coverage increased in the city, mainly after 15 000 inhabitants were vaccinated (35.21% of the population) in July 2021. At the time, 49.06% of administered vaccines were ChAdOx1-S recombinant, 39.80% inactivated SARS-CoV-2 virus (CZ02 strain), 9.70% Tozinameran, and 1.44% Ad26.COV2-S recombinant. From August 2021, a marked reduction in daily positive cases and deaths was observed, and incidence (≤2.49 per 1000 inhabitants) and mortality (≤0.02 per 1000 inhabitants) rates remained stabilized until January 2022, when a new outbreak occurred upon the emergence of the Omicron variant. However, the mortality rate (0.07 per 1000 inhabitants) remained low regardless of the Omicron high incidence rate (68.41 per 1000 inhabitants). These data demonstrate the COVID-19 vaccination effectiveness with a threshold of 35.21% of the population vaccinated in this city model., (© 2023 Wiley Periodicals LLC.)

Objectives: Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity., Methods: A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used., Results: A total of 264 volunteers were included for analysis (BCG = 134 and placebo = 130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60% × 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance., Conclusion: Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941)., Competing Interests: Declaration Of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Brazil experienced moments of collapse in its health system throughout 2021, driven by the emergence of variants of concern (VOC) combined with an inefficient initial vaccination strategy against Covid-19., Objectives: To support decision-makers in formulating COVID-19 immunization policy in the context of limited vaccine availability and evolving variants over time, we evaluate optimal strategies for Covid-19 vaccination in Brazil in 2021, when vaccination was rolled out during Gamma variant predominance., Methods: Using a discrete-time epidemic model we estimate Covid-19 deaths averted, considering the currently Covid-19 vaccine products and doses available in Brazil; vaccine coverage by target population; and vaccine effectiveness estimates. We evaluated a 5-month time horizon, from early August to the end of December 2021. Optimal vaccination strategies compared the outcomes in terms of averted deaths when varying dose intervals from 8 to 12 weeks, and choosing the minimum coverage levels per age group required prior to expanding vaccination to younger target populations. We also estimated dose availability required over time to allow the implementation of optimal strategies., Results: To maximize the number of averted deaths, vaccine coverage of at least 80 % should be reached in older age groups before starting vaccination into subsequent younger age groups. When evaluating varying dose intervals for AZD1222, reducing the dose interval from 12 to 8 weeks for the primary schedule would result in fewer COVID-19 deaths, but this can only be implemented if accompanied by an increase in vaccine supply of at least 50 % over the coming six-months in Brazil., Conclusion: Covid-19 immunization strategies should be tailored to local vaccine product availability and supply over time, circulating variants of concern, and vaccine coverage in target population groups. Modelling can provide valuable and timely evidence to support the implementation of vaccination strategies considering the local context, yet following international and regional technical evidence-based guidance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Describe a case series of vaccine-induced immune thrombotic thrombocytopenia (VITT) after COVID-19 vaccination in Brazil that included ChAdOx1 nCoV-19, Ad26.COV2.S and BNT162b2 vaccines, describing their clinical and laboratory characteristics., Methodology: Descriptive case series study using Bio-Manguinhos/Fiocruz/AstraZeneca Brazil and National Immunization Program/Ministry of Health (NIP/MoH) data on COVID-19 AEFI surveillance. We obtained patient-level data from pharmacovigilance for AEFI surveillance and used both the NIP/MoH and Bio-Manguinhos/Fiocruz pharmacovigilance databases to create the study database. Thirty-nine cases of suspect VITT were included, 36 after ChAdOx1 nCoV-19, one after BNT162b2 and two after Ad26.COV2.S vaccine. All cases were based on meeting the Brighton Collaboration criteria for VITT. The primary outcomes were clinical and laboratory features, site of thrombosis, and anti-PF4 ELISA, when available., Results: Thirty-nine cases met the criteria, 38 of which were classified as level 1 and one as level 3 according to Brighton Collaboration. Most cases had the central nervous system (CNS) as the main site of thrombosis (21/39) and happened after the vaccine first dose (34/39). The median age of the cases was 41 years old (23 to 86 yo). Most of the cases (61.5%) occurred in women. The median interval between vaccination and onset of symptoms was 8 days (0-37 days). The platelet count and D-dimer count had median values of 34,000/µL and 19,235 µg FEU/L, respectively. The ELISA anti-PF4 antibody was positive in 18 samples. The overall mortality rate was 51% and was higher in cases of CNS thrombosis with intracerebral bleeding., Conclusion: Our case series shows that Brazilian VITT cases have similar clinical and laboratory profiles as demonstrated in the literature. Brazil has administered more than 300 million doses of COVID-19 vaccines (more than 110 million from ChAdOx1 nCoV-19). VITT seems to be a very rare but serious adverse event following COVID-19 immunization, especially adenoviral vector immunization., Competing Interests: Declaration of Competing Interest Patricia Mouta Nunes de Oliveira ,Catherine Crespo Cordeiro, Debora Lima Abreu, Gabriellen Vitiello Teixeira, Janaina Reis Xavier, Letícia Kegele Lignani, Livia Neves Waite Freitas, Maria de Lourdes de Sousa Maia, Michael Bernardes Ramos, Patricia Mouta Nunes de Oliveira, Paulo Roberto Gomes Takey, Renata Saraiva Pedro, Tainá dos Santos Pereira, and Vitor Cardoso da Gama are employees of the Immunobiological Technology Institute/Oswaldo Cruz Foundation (Bio-Manguinhos/Fiocruz), Marketing Authorization Holder of the covid-19 vaccine (recombinant)* in Brazil.  Bárbara Emoingt Furtado and André Santa Maria reports a relationship with AstraZeneca Brasil that includes: employment. employee of AstraZeneca Brasil , Marketing Authorization Holder of the covid-19 vaccine (recombinant)* in Brazil.  The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of interests MB-N reports grants from the Fazer o Bem Faz Bem programme from JBS. AIK reports grants from Bristol Myers Squibb, Regeneron, and Serimmune; and grants and personal fees from Tata Medical Devices, outside the submitted work. VdAO, VSB, MLB, JC, and MB-N are employees of Fiocruz, a federal public institution, which manufactures Vaxzevria (ChAdOx1 nCoV-19 vaccine) in Brazil through a full technology transfer agreement with AstraZeneca. Fiocruz allocates all its manufactured products to the Ministry of Health for public health use. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To estimate vaccine effectiveness after the first and second dose of ChAdOx1 nCoV-19 against symptomatic COVID-19 and infection in a socially vulnerable community in Brazil when Gamma and Delta were the predominant variants circulating., Methods: We conducted a test-negative study in the community Complexo da Maré, the largest group of slums (n = 16) in Rio de Janeiro, Brazil, from January 17, 2021 to November 27, 2021. We selected RT-qPCR positive and negative tests from a broad community testing program. The primary outcome was symptomatic COVID-19 (positive RT-qPCR test with at least one symptom) and the secondary outcome was infection (any positive RT-qPCR test). Vaccine effectiveness was estimated as 1 - OR, which was obtained from adjusted logistic regression models., Results: We included 10 077 RT-qPCR tests (6,394, 64% from symptomatic and 3,683, 36% from asymptomatic individuals). The mean age was 40 (SD: 14) years, and the median time between vaccination and RT-qPCR testing among vaccinated was 41 (25-75 percentile: 21-62) days for the first dose and 36 (25-75 percentile: 17-59) days for the second dose. Adjusted vaccine effectiveness against symptomatic COVID-19 was 31.6% (95% CI, 12.0-46.8) 21 days after the first dose and 65.1% (95% CI, 40.9-79.4) 14 days after the second dose. Adjusted vaccine effectiveness against COVID-19 infection was 31.0% (95% CI, 12.7-45.5) 21 days after the first dose and 59.0% (95% CI, 33.1-74.8) 14 days after the second dose., Discussion: ChAdOx1 nCoV-19 was effective in reducing symptomatic COVID-19 in a socially vulnerable community in Brazil when Gamma and Delta were the predominant variants circulating., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses., Methods: RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer-BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18-60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR-9nn3scw., Findings: Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8-30·1) in adults aged 18-60 years and 8·9% (4·2-16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67-88) for Ad26.COV2-S, 152 (134-173) for BNT162b2, 90 (77-104) for ChAdOx1 nCoV-19, and 12 (11-14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8-7·7) for Ad26.COV2-S, 13·4 (11·6-15·3) for BNT162b2, and 7·0 (6·1-8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9-12·9) for Ad26.COV2-S vaccine, 21·5 (14·5-31·9) for BNT162b2, and 10·6 (7·2-15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home., Interpretation: Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection., Funding: Ministry of Health, Brazil., Competing Interests: Declaration of interests AJP is chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts. AJP is an National Institute for Health Research Senior Investigator. TL is named as an inventor on a patent application covering ChAdOx1 nCoV-19. Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Brazil is one of the epicenters of COVID-19 pandemic and faces several hindrances to make his COVID-19 vaccination plan efficient., Methods: The Brazilian COVID-19 vaccination plan was evaluated and the hindrances to make the COVID-19 vaccination plan efficient were described and discussed., Results: High territorial extension might contribute to a delay on the COVID-19 vaccination, due to difficulty in delivering vaccines to furthest Brazilian states and to all the interior cities. The choice among the vaccines should be done based on the type of storage and must consider the transport conditions necessary to maintain its effectiveness. The indigenous individuals were included with health-care workers as the first group to be vaccinated, inflaming the number of vaccines doses distributed in states where the indigenous population have higher prevalence. The antivaccine movement and the politicization of the vaccine are also hindrances to be overcome in Brazil. The COVID-19 incidence or mortality rate and the distribution of intensive care units (ICUs) are not a criterion to distribute the vaccines, as we did not identify a correlation between these markers and the number of vaccines. However, a strong or very strong correlation occurred between the number of COVID-19 vaccines and the number of COVID-19 cases, deaths by COVID-19, gross domestic product, as well as populational density. A total of 83,280,475 doses of COVID-19 vaccines were distributed in Brazil. In the first dose, the Coronavac (Sinovac™), AZD1222 (AstraZeneca/Oxford™), and BNT162b (Pfizer/BioNTech™) vaccines were responsible to vaccinate, respectively, 9.61%, 6.69%, and 0.35% of the Brazilian population. In the second dose, the Coronavac, AZD1222, and BNT162b vaccines were responsible to vaccinate, respectively, 7.52%, 0.53%, and <0.01% of the Brazilian population., Conclusions: The Federal Government must evaluate the hindrances and propose solutions to maximize the immunization against COVID-19 on Brazil.

Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (-2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K., (© 2021. The Author(s).)

Introduction: The quick spread of SARS-CoV-2 led to the development of vaccines that are capable of reducing infection and the number of more severe COVID-19 cases., Aim: To assess COVID-19 prevalence among healthcare workers (HCWs) after vaccination against SARS-CoV-2., Methods: This was a cross-sectional study on the prevalence of COVID-19 diagnosis among 7523 HCWs vaccinated against SARS-CoV-2 with CoronaVac and ChAdOx1 nCoV-19 in a university hospital, in southern Brazil, between January 18 and March 18, 2021.The variables evaluated were: sex, age, work area, role, source of infection, previous diagnosis of COVID-19, date of vaccine administration, type of vaccine, and need for hospitalization. The statistical analysis used Poisson regression and Fisher's exact test with SPSS software version 25, and a level of significance set at 5%., Results: 813 vaccinated HCWs showed symptoms suggestive of COVID-19, of whom 35.4% (288) had a detectable result after undergoing RT-PCR for SARS-CoV-2. There was a reduction of 62% in new cases of COVID-19 among HCWs in the institution 7 weeks after the start of vaccine rollout., Conclusion: Our data suggest that the vaccines used by the institution reduced the number of COVID-19 cases among healthcare workers, demonstrating the effectiveness of the vaccines., Competing Interests: Declaration of Competing Interest The researchers declare that they have no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Coronavirus disease-2019 (COVID-19), associated with the outbreak of deadly virus originating in Wuhan, China, is now a global health emergency and a matter of serious concern. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is rapidly spreading worldwide, and WHO declared the outbreak of this disease a pandemic on March 11, 2020. Though some of the countries have succeeded in slowing down the rate of the spread of this pandemic, most the countries across the globe are still continuing to experience an increasing trend in the growth and spread of this deadly disease. Hence, in the current scenario, is has now become essential to control and finally irradicate this deadly disease using an effective vaccine. One can expect the prominent role of already available antivirals, antibodies and anti-inflammatory drugs in the market, in this pandemic. Immunomodulatory and biological therapeutics are also in the high expectations to combat COVID-19. RNA based vaccines might be more advantageous over traditional vaccines, to deal with the pandemic threat. Aiming towards this direction, clinical trials for SARS-CoV-2 vaccine are currently underway all across the globe. Currently, about 150 health related organizations and research labs are in the progress for the evolution of COVID-19 vaccines, globally. The initial aim of these clinical trials is to assess vaccine's safety, which is tested in Phase I/II/III studies where the primary outcomes typically examine the frequency of adverse effects. The vaccine is about to undergo phase III testing in several countries such as India, USA, South Africa, Brazil and England. US Government, under Operation Wrap Speed is even ready to sponsor three candidates, namely-The University of Oxford and AstraZeneca's AZD1222; Moderna's mRNA-1273; and Pfizer and BioNTech's BNT162 for Phase III trials., (Copyright © 2021. Published by Elsevier Ltd.)

Source Citation: Voysey M, Clemens SA, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397:99-111. 33306989.

Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials., Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 10 10 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674., Findings: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation., Interpretation: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials., Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)