Effect of Tele-ICU on Clinical Outcomes of Critically Ill Patients: The TELESCOPE Randomized Clinical Trial.

Importance: Despite its implementation in several countries, there has not been a randomized clinical trial to assess whether telemedicine in intensive care units (ICUs) could improve clinical outcomes of critically ill patients. Objective: To determine whether an intervention comprising daily multidisciplinary rounds and monthly audit and feedback meetings performed by a remote board-certified intensivist reduces ICU length of stay (LOS) compared with usual care. Design, Setting, and Participants: A parallel cluster randomized clinical trial with a baseline period in 30 general ICUs in Brazil in which daily multidisciplinary rounds performed by board-certified intensivists were not routinely available. All consecutive adult patients (aged ≥18 years) admitted to the participating ICUs, excluding those admitted due to justice-related issues, were enrolled between June 1, 2019, and April 7, 2021, with last follow-up on July 6, 2021. Intervention: Remote daily multidisciplinary rounds led by a board-certified intensivist through telemedicine, monthly audit and feedback meetings for discussion of ICU performance indicators, and provision of evidence-based clinical protocols. Main Outcomes and Measures: The primary outcome was ICU LOS at the patient level. Secondary outcomes included ICU efficiency, in-hospital mortality, incidence of central line-associated bloodstream infections, ventilator-associated events, catheter-associated urinary tract infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation, and rate of patients with oxygen saturation values under that of normoxemia, assessed using generalized linear mixed models. Results: Among 17 024 patients (1794 in the baseline period and 15 230 in the intervention period), the mean (SD) age was 61 (18) years, 44.7% were female, the median (IQR) Sequential Organ Failure Assessment score was 6 (2-9), and 45.5% were invasively mechanically ventilated at admission. The median (IQR) time under intervention was 20 (16-21) months. Mean (SD) ICU LOS, adjusted for baseline assessment, did not differ significantly between the tele-critical care and usual care groups (8.1 [10.0] and 7.1 [9.0] days; percentage change, 8.2% [95% CI, -5.4% to 23.8%]; P = .24). Results were similar in sensitivity analyses and prespecified subgroups. There were no statistically significant differences in any other secondary or exploratory outcomes. Conclusions and Relevance: Daily multidisciplinary rounds conducted by a board-certified intensivist through telemedicine did not reduce ICU LOS in critically ill adult patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03920501.

Prevalence, risk factors, and impact of long COVID in a socially vulnerable community in Brazil: a prospective cohort study.

Background: Long COVID is an emerging global public health issue. Socially vulnerable communities in low- and-middle-income countries were severely impacted by the pandemic and are underrepresented in research. This prospective study aimed to determine the prevalence of long COVID, its impact on health, and associated risk factors in one such community in Rio de Janeiro, Brazil. Methods: A total of 710 individuals aged 18 and older, with confirmed SARS-CoV-2 infection at least three months prior, were enrolled between November 25, 2021, and May 5, 2022. Participants were assessed via telephone or in person using a standardized questionnaire to evaluate their perception of recovery, symptoms, quality of life, and functional status. Findings: Twenty percent of participants did not feel fully recovered, 22% experienced new or persistent symptoms, 26% had worsened functional status, 18% had increased dyspnoea, and 32% reported a worse quality of life. Persistent symptoms included headache, cough, fatigue, muscle pain, and shortness of breath. Dyspnoea during the acute phase was the strongest independent predictor of worsening outcomes. Females and individuals with comorbidities were more likely to report worse recovery, functioning, dyspnoea, and quality of life. Interpretation: Our findings reveal a high burden of severe and persistent physical and mental health sequelae in a socially vulnerable community following COVID-19. Funding: UK Foreign, Commonwealth and Development Office and Wellcome Trust Grant (222048/Z/20/Z), Fundação Oswaldo Cruz (FIOCRUZ), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and the Centers for Disease Control and Prevention (CDC).

Effectiveness of COVID-19 vaccines against severe COVID-19 among patients with cancer in Catalonia, Spain.

Patients with cancer were excluded from pivotal randomized clinical trials of COVID-19 vaccine products, and available observational evidence on vaccine effectiveness (VE) focused mostly on mild, and not severe COVID-19, which is the ultimate goal of vaccination for high-risk groups. Here, using primary care electronic health records from Catalonia, Spain (SIDIAP), we built two large cohorts of vaccinated and matched control cancer patients with a primary vaccination scheme (n = 184,744) and a booster (n = 108,534). Most patients received a mRNA-based product in primary (76.2%) and booster vaccination (99.9%). Patients had 51.8% (95% CI 40.3%-61.1%) and 58.4% (95% CI 29.3%-75.5%) protection against COVID-19 hospitalization and COVID-19 death respectively after full vaccination (two-doses) and 77.9% (95% CI 69.2%-84.2%) and 80.2% (95% CI 63.0%-89.4%) after booster. Compared to primary vaccination, the booster dose provided higher peak protection during follow-up. Calibration of VE estimates with negative outcomes, and sensitivity analyses with slight different population and COVID-19 outcomes definitions provided similar results. Our results confirm the role of primary and booster COVID-19 vaccination in preventing COVID-19 severe events in patients with cancer and highlight the need for the additional dose in this population.

Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study.

Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Vaccine coverage and effectiveness against laboratory-confirmed symptomatic and severe Covid-19 in indigenous people in Brazil: a cohort study.

BACKGROUND: Indigenous people have historically suffered devastating impacts from epidemics and continue to have lower access to healthcare and be especially vulnerable to respiratory infections. We estimated the coverage and effectiveness of Covid-19 vaccines against laboratory-confirmed Covid-19 cases among indigenous people in Brazil. METHODS: We linked nationwide Covid-19 vaccination data with flu-like surveillance records and studied a cohort of vaccinated indigenous people aged ≥ 5 years between 18th January 2021 and 1st March 2022. We considered individuals unexposed from the date they received the first dose of vaccine until the 13th day of vaccination, partially vaccinated from the 14th day after the first dose until the 13th day after receiving the second dose, and fully vaccinated onwards. We estimated the Covid-19 vaccination coverage and used Poisson regression to calculate the relative risks (RR) and vaccine effectiveness (VE) of CoronaVac, ChAdOx1, and BNT162b2 against Covid-19 laboratory-confirmed cases incidence, mortality, hospitalisation, and hospital-progression to Intensive Care Unit (ICU) or death. VE was estimated as (1-RR)*100, comparing unexposed to partially or fully vaccinated. RESULTS: By 1st March 2022, 48.7% (35.0-62.3) of eligible indigenous people vs. 74.8% (57.9-91.8) overall Brazilians had been fully vaccinated for Covid-19. Among fully vaccinated indigenous people, we found a lower risk of symptomatic cases (RR: 0.47, 95%CI: 0.40-0.56) and mortality (RR: 0.47, 95%CI: 0.14-1.56) after the 14th day of the second dose. VE for the three Covid-19 vaccines combined was 53% (95%CI:44-60%) for symptomatic cases, 53% (95%CI:-56-86%) for mortality and 41% (95%CI:-35-75%) for hospitalisation. In our sample, we found that vaccination did not reduce Covid-19 related hospitalisation. However, among hospitalised patients, we found a lower risk of progression to ICU (RR: 0.14, 95%CI: 0.02-0.81; VE: 87%, 95%CI:27-98%) and Covid-19 death (RR: 0.04, 95%CI:0.01-0.10; VE: 96%, 95%CI: 90-99%) after the 14th day of the second dose. CONCLUSIONS: Lower coverage but similar Covid-19 VE among indigenous people than overall Brazilians suggest the need to expand access, timely vaccination, and urgently offer booster doses to achieve a great level of protection among this group.

Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.

INTRODUCTION: Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (Complexo da Maré) in Rio de Janeiro, Brazil. METHODS: We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in Maré, before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in Maré. RESULTS: Before the intervention, Maré presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, Maré displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in Maré and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in Maré after intervention onset. CONCLUSION: An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.

What we talk about when we talk about COVID-19 vaccination campaign impact: a narrative review.

Background: The lack of precise definitions and terminological consensus about the impact studies of COVID-19 vaccination leads to confusing statements from the scientific community about what a vaccination impact study is. Objective: The present work presents a narrative review, describing and discussing COVID-19 vaccination impact studies, mapping their relevant characteristics, such as study design, approaches and outcome variables, while analyzing their similarities, distinctions, and main insights. Methods: The articles screening, regarding title, abstract, and full-text reading, included papers addressing perspectives about the impact of vaccines on population outcomes. The screening process included articles published before June 10, 2022, based on the initial papers' relevance to this study's research topics. The main inclusion criteria were data analyses and study designs based on statistical modelling or comparison of pre- and post-vaccination population. Results: The review included 18 studies evaluating the vaccine impact in a total of 48 countries, including 32 high-income countries (United States, Israel, and 30 Western European countries) and 16 low- and middle-income countries (Brazil, Colombia, and 14 Eastern European countries). We summarize the main characteristics of the vaccination impact studies analyzed in this narrative review. Conclusion: Although all studies claim to address the impact of a vaccination program, they differ significantly in their objectives since they adopt different definitions of impact, methodologies, and outcome variables. These and other differences are related to distinct data sources, designs, analysis methods, models, and approaches.

Effectiveness of an inactivated Covid-19 vaccine with homologous and heterologous boosters against Omicron in Brazil.

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6-11.5) and 56.8% (95% CI, 56.3-57.3) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9-80.7) and 86.0% (95% CI, 84.5-87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.

Primary healthcare protects vulnerable populations from inequity in COVID-19 vaccination: An ecological analysis of nationwide data from Brazil.

Background: There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage. Methods: We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels. Findings: From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations. Interpretation: In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations. Funding: This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.

One Health and surveillance of zoonotic tuberculosis in selected low-income, middle-income and high-income countries: A systematic review.

BACKGROUND: Little is known about zoonotic tuberculosis (zTB) due to Mycobacterium bovis burden across the globe. The aim of this study was to describe zTB surveillance programs in selected WHO signatory countries and to assess the relationship of the disease with the country's income level and the risk of M. bovis transmission. METHODS: We searched the main articles databases and grey literature for guide documents published between 1980 and 2019. For inclusion, the articles and guide documents had to be in English, French, Portuguese, Spanish, or Italian. Only original articles and narrative and systematic reviews were accepted and the guide documents were required to be available on official websites. We excluded articles that did not focus on epidemiology, control and surveillance. We used bovine TB cases in livestock and wildlife populations as a proxy for the country's risk of zTB using data from the World Organization for Animal Health (OIE) published from 2015 to 2018. Countries were classified according to income level (World Bank's classification) and strength of zTB surveillance. The study was registered in PROSPERO under number CRD42018090603. FINDINGS: We included 13 articles and 208 guide documents including data from 119/194 countries (61.3%). We found a lack of surveillance data about zTB in over half (89.9%) of the 119 WHO signatory countries. Most surveillance systems perform passive surveillance and are not integrated into the One Health perspective, which was operating in 4/119 (3.4%) countries, all high-income. Many of these countries (71/119, 59.7%) have M. bovis circulating in their cattle herds, but only ~10% of them have implemented zTB surveillance activities. INTERPRETATION: Our findings highlight weaknesses in zTB surveillance worldwide, with a consequent lack of information that could support an adequate understanding of disease burden, especially in countries at major risk for M. bovis transmission. To meet this challenge, efforts will be needed to promote intersectoral policies, implementing the One Health strategy.

Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study.

OBJECTIVE: To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine CoronaVac (Sinovac Biotech) in São Paulo State, Brazil. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo State, Brazil. PARTICIPANTS: Adults aged ≥18 years who were residents of São Paulo state, had received two doses of CoronaVac, did not have a laboratory confirmed SARS-CoV-2 infection before vaccination, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 14 December 2021. Cases were matched to test negative controls by age (in 5 year bands), municipality of residence, healthcare worker status, and epidemiological week of RT-PCR test. MAIN OUTCOME MEASURES: RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Conditional logistic regression was adjusted for sex, number of covid-19 associated comorbidities, race, and previous acute respiratory illness. RESULTS: From 202 741 eligible people, 52 170 cases with symptomatic covid-19 and 69 115 test negative controls with covid-19 symptoms were formed into 43 257 matched sets. Adjusted odds ratios of symptomatic covid-19 increased with time since completion of the vaccination series. The increase in odds was greater in younger people and among healthcare workers, although sensitivity analyses suggested that this was in part due to bias. In addition, the adjusted odds ratios of covid-19 related hospital admission or death significantly increased with time compared with the odds 14-41 days after series completion: from 1.25 (95% confidence interval 1.04 to 1.51) at 70-97 days up to 1.94 (1.41 to 2.67) from 182 days onwards. CONCLUSIONS: Significant increases in the risk of moderate and severe covid-19 outcomes occurred three months after primary vaccination with CoronaVac among people aged 65 and older. These findings provide supportive evidence for the implementation of vaccine boosters in these populations who received this inactivated vaccine. Studies of waning should include analyses designed to uncover common biases.

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 ChAdOx1 nCoV-19 against COVID-19 in a socially vulnerable community in Rio de Janeiro, Brazil: a test-negative design study.

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.

Determination of Anti-Phospholipase A2 and Anti-Thrombospondin Type 1 Domain-Containing Protein 7A in Latin Patients with Membranous Nephropathy.

Primary membranous nephropathy (MN) is caused by antibodies against podocyte antigens, especially the type M receptor of phospholipase A2 (PLA2R) and thrombospondin type-1 domain containing 7 A (THSD7A). This study's aim was the determination of anti-PLA2R, anti-THSD7A serum antibodies, and anti-PLA2R renal tissue staining prevalence in a Latin population with MN, as well as evaluating their role as biomarkers for disease activity. The performance of the two anti-PLA2R serum diagnostic methods-ELISA and indirect immunofluorescence (IFI)-was evaluated for the diagnosis of MN. Fifty-nine patients, including 29 with MN, 18 with lupus membranous nephropathy (LMN) and 12 with focal and segmental glomerulosclerosis (FSGS), were evaluated for serum antibodies. Renal biopsies were also evaluated for the presence of anti-PLA2R staining. Twenty-one patients with MN were followed for 1 year. Patients with LMN and FSGS were negative for both antibodies. All 29 MN patients were negative for anti-THSD7A; 16 MN patients were positive for anti-PLA2R by ELISA and/or IFI, and 3 MN patients were positive for anti-PLA2R only by IFI. Thus, the anti-PLA2R ELISA test demonstrated 45% sensitivity and 97% specificity, while the IFI test showed, respectively, 55% and 100% in our MN patients. Among the 28 MN renal biopsies, 20 presented anti-PLA2R positive staining, corresponding to a 72% sensitivity. Positive correlations were observed between the anti-PLA2R ELISA titer and proteinuria. In conclusion, determination of anti-PLA2R antibodies in the MN Latin population showed similar rates to those reported for other populations. The anti-PLA2R serum levels correlated with MN disease activity.

Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo.

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4-39.7) against Covid-19, 55.1% (95% CI, 46.6-62.2) against hospitalization, and 61.8% (95% CI, 48.9-71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2-84.2) against Covid-19, 87.6% (95% CI, 78.2-92.9) against hospitalization, and 93.6% (95% CI, 81.9-97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.

Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. METHODS: We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. FINDINGS: For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. INTERPRETATION: Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. FUNDING: Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas.