Time between symptom and testing in relation to familial transmission of severe acute respiratory syndrome coronavirus 2.

Brazil has a huge number of cases and deaths due to coronavirus disease 2019 (COVID-19); however, few studies have dealt with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among familial contacts in Brazil. Here, we report our findings on transmission in a family-based study in Bauru, São Paulo, Brazil. The study, conducted from July to November 2020, comprised 974 individuals with 233 index patients and 741 familial contacts. Familial contacts were evaluated using the rapid COVID-19 Ag ECO and reverse transcription-polymerase chain reaction (RT-PCR) tests immediately after the index patient diagnosis. The antigen-based rapid test was validated in 121 individuals using RT-PCR as the gold standard. Additionally, 30 days later, familial contacts were evaluated for IgM and IgG antibodies against SARS-CoV-2. We found 333 cases of COVID-19 among familial contacts (44.9%). A positive correlation was observed between the time elapsed from the onset of symptoms until the index patient's COVID-19 testing and the number of family contacts infected by SARS-CoV-2. Early SARS-CoV-2 testing and familial contact evaluation are relevant strategies to contain transmission.

Acquisition of carbapenem-resistant gram-negative bacilli among intensive care unit (ICU) patients with no previous use of carbapenems: Indirect population impact of antimicrobial use.

OBJECTIVE: To measure the impact of exposure to patients using carbapenem on the acquisition of carbapenem-resistant gram-negative bacilli (CR-GNB) among patients not using carbapenems. DESIGN: An ecological study and a cohort study. SETTING: Two medical surgical intensive care units (ICUs) in inner Brazil. PARTICIPANTS: Patients admitted to 2 ICUs from 2013 through 2018 to whom carbapenem was not prescribed. METHODS: In the ecologic study, the monthly use of carbapenems (days of therapy [DOT] per 1,000 patient days) was tested for linear correlation with the 2-month moving average of incidence CR-GNB among patients to whom carbapenem was not prescribed. In the cohort study, those patients were addressed individually for risk factors (demographics, invasive interventions, use of antimicrobials) for acquisition of CR-GNB, including time at risk and the "carbapenem pressure," described as the aggregate DOT among other ICU patients during time at risk. The analysis was performed in univariate and multivariable Poisson regression models. RESULTS: The linear regression model revealed an association of total carbapenem use and incidence of CR-GNB (coefficient, 0.04; 95% confidence interval [CI], 0.02-0.06; P = .001). In the cohort model, the adjusted rate ratio (RR) for carbapenem DOT was 1.009 (95% CI, 1.001-1.018; P = .03). Other significant risk factors were mechanical ventilation and the previous use of ceftazidime (with or without avibactam). CONCLUSIONS: Every additional DOT of total carbapenem use increased the risk of CR-GNB acquisition by patients not using carbapenems by nearly 1%. We found evidence for a population ("herd effect"-like) impact of antimicrobial use in the ICUs.

Effectiveness of the Fiocruz recombinant ChadOx1-nCoV19 against variants of SARS-CoV-2 in the Municipality of Botucatu-SP.

Introduction: As the COVID-19 pandemic progresses, rapidly emerging variants of concern raise fears that currently licensed vaccines may have reduced effectiveness against these new strains. In the municipality of Botucatu, São Paulo State, Brazil, a mass vaccination campaign using ChadOx1-nCoV19 was initiated on 16th of May 2021, targeting people 18-60 years old. Two vaccine doses were offered 12 weeks apart, with the second delivered on 8th of August, 2021. This setting offered a unique opportunity to assess the effectiveness of two ChadOx1-nCoV19 doses in a real-life setting. Materials and methods: Data on testing, hospitalization, symptoms, demographics, and vaccination were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu. A test-negative study design was employed; whereby the odds of being vaccinated among cases vs controls were calculated to estimate vaccine effectiveness (VE; 1-OR). All individuals aged 18-60 who received a PCR test after the 16th of May and were unvaccinated prior to this date were included in the analysis until the study ended in mid-November 2021. Results: 77,683 citizens of Botucatu aged 18-60 received the first dose, and 74,051 received a second ChadOx1-nCoV19 dose 12 weeks later for a vaccination coverage of 84.2 and 80.2%, respectively. Of 7.958 eligible PCR tests, 2.109 were positive and 5.849 negative. The VE against any symptomatic infection was estimated at 39.2%, 21 days after dose 1, and 74.5%, 14 days after dose 2. There were no COVID-19-related hospitalizations or deaths among the 74,051 fully vaccinated individuals. The VE against severe disease was estimated at 70.8 and 100% after doses 1 and 2, respectively. 90.5% of all lineages sequenced between doses 1 and 2 (16th of May-7th of August) were of the Gamma variant, while 83.0% were of the Delta variant during the second period after dose 2 (8th of August-18th of November). Discussion: This observational study found the effectiveness of ChadOx1-nCoV19 to be 74.5% against COVID-19 disease of any severity, comparable to the efficacy observed in clinical trials (81.3% after dose 2), despite the dominance of the Gamma and Delta VoCs. No COVID-19-related hospitalizations or deaths in fully vaccinated individuals were reported.

COVID-19 and isolation: Risks and implications in the scenario of new variants.

With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.

Safety of the Fiocruz ChAdOx COVID-19 vaccine used in a mass vaccination campaign in Botucatu, Brazil.

INTRODUCTION: Brazil has been at the core of the COVID-19 pandemic, with the second-highest death toll worldwide. A mass vaccination campaign was initiated on May 16th, 2021, in Botucatu, Brazil, where two doses of ChadOx1-nCoV19 were offered 12 weeks apart to all 18-60- year-olds. This context offers a unique opportunity to study the vaccine safety during a mass campaign. METHODS: The first and second doses of the vaccine were administered in May and August 2021, respectively. Emergency room (ER) and hospitalization records were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu for six weeks before and six weeks after the first and second doses, from 4 April to 19 September 2021. Diagnoses with COVID-19-related ICD codes were excluded to distinguish any trends resulting from the COVID-19 pandemic. ER and hospital visits during the two time periods were compared, including an ICD code comparison, to identify any changes in disease distributions. Data were scanned for a defined list of Adverse Events of Special Interest (AESIs), as presented by the Safety Platform for Emergency Vaccines. RESULTS AND DISCUSSION: A total of 77,683 and 74,051 subjects received dose 1 and dose 2 of ChadOx1-nCoV19, respectively. Vaccination was well tolerated and not associated with any major safety concerns. Increases in ER visits 1 week following both doses were primarily seen in ICD codes related to non-serious side effects of the vaccine, including vaccination site pain and other local events. The neurological AESIs identified (2 of 3 cases of multiple sclerosis) were relapses of a pre-existing condition. One potentially serious hospitalization event for Bell's palsy had onset before vaccination with dose 1, in a patient who also had a viral infection of the central nervous system. There was no myocarditis, pericarditis cases, or vaccine-related increases in thromboembolic events.

INDICAÇÃO DE PAINEL RESPIRATÓRIO PARA DETECÇÃO DE INFECÇÕES RESPIRATÓRIAS VIRAIS EM PESSOAS QUE VIVEM COM HIV/AIDS

Introdução Emergências em saúde pública de importância internacional requerem rápidas respostas da ciência para nortear decisões estratégicas em políticas públicas. A pandemia de Covid- 19 é a emergência de saúde pública mais dramática da história recente. Um grupo particularmente suscetível a doenças gripais com possibilidade de evolução grave são as pessoas que vivem com HIV/AIDS (PHVA), em especial aqueles com baixa contagem de células T CD4+. Atualmente, existem cerca de 37,9 milhões de PVHA no mundo. Objetivo O objetivo deste trabalho foi indicar um painel respiratório com 24 vírus causadores de doenças respiratórias, a fim de auxiliar na detecção rápida de possíveis patógenos nas pessoas que vivem com HIV/AIDS. Métodos a partir de 15 amostras obtidas de nasofaringe e/ou orofaringe foram extraídos os materiais genéticos virais utilizando o Kit Biopur de extração (Mini Spin Vírus DNA/RNA 2.0 Flow Chip). O material genético extraído foi amplificado por PCR seguida de hibridizações correspondentes a 24 diferentes vírus respiratórios utilizando o Kit Multiplex PR24 Flow Chip automatizado - 24RX com leitura automatizada no equipamento Hybrispot 12 PCR AUTO. Resultados Das 15 amostras analisadas de indivíduos vivendo com HIV/AIDS,10 foram detectadas para SARS-COV-2, uma detectada para vírus sincicial respiratório humano (RSV), uma para Corona 229-E, e em uma foi identificada coinfecção de bocavírus e coronavírus SARS-LIKE. Conclusão A utilização do painel respiratório pode auxiliar na detecção rápida para vírus respiratórios mais específicos, uma vez que pessoas que vivem com HIV/AIDS estão mais imunossuprimidas e susceptíveis a tais infecções, tornando assim o painel respiratório um grande aliado no diagnóstico diferencial rápido.

Factors associated with COVID-19 mortality in municipalities in the state of São Paulo (Brazil): an ecological study.

BACKGROUND: The mortality rate of coronavirus disease (COVID-19) in the state of São Paulo is highly heterogeneous. This study investigated geographic, economic, social, and health-related factors associated with this discrepancy. METHODS: An ecological study compared COVID-19 mortality rates according to geographic, economic, social, and health-related variables during initial infection of 2.5% of the population in municipalities with more than 30,000 inhabitants. RESULTS: Mortality was positively associated with demographic density and social inequality (Gini index), and inversely associated with HDI income and longevity of these municipalities, accounting for 33.2% of the variation in mortality. CONCLUSIONS: Social determinants influenced COVID-19 outcomes.

Inactivated Whole-virus Vaccine Triggers Low Response Against SARS-CoV-2 Infection Among Renal Transplant Patients: Prospective Phase 4 Study Results.

BACKGROUND: Anti-severe acute respiratory syndrome coronavirus 2 mRNA vaccines elicit lower humoral responses in solid-organ transplant recipients. This is the first prospective trial investigating the effect of an inactivated whole-virion vaccine in kidney transplant recipients. METHODS: Prospective, single-center, phase 4, interventional study. Kidney transplant recipients aged 30-69 y with >30 d of transplantation received two 3 µg intramuscular doses of CoronaVac 28 d apart and are being followed for 6 mo. Primary outcomes: (1) reactogenicity after first dose; (2) antibody responses 28 d after each dose; and (3) incidence/severity of confirmed coronavirus disease 2019 (COVID-19) and 28-d lethality rate. For this analysis, clinical effectiveness was assessed for 3 mo, starting 15 d after the second dose, and compared with 3-mo period before vaccination. RESULTS: Of the 3371 individuals who received the first dose, 99% completed vaccination schedule. Mild/local adverse reactions were reported by 33% of the patients. In the immunogenicity cohort (n = 942), the proportion of patients with IgG antibodies to severe acute respiratory syndrome coronavirus 2 increased from 15.2% after first dose to 43% after second dose. Increase in antibody values after second dose was associated with higher proportion of patients with detected neutralizing antibodies. A significant reduction in the incidence of COVID-19 was observed (6.4% versus 4.2%; P < 0.0001), although the 28-d lethality rate remained unchanged (25% versus 22%; P = 0.534). In 45 patients from the immunogenicity cohort who developed COVID-19, all the 6 deaths occurred among those without antibody response (n = 22; 49%). CONCLUSIONS: CoronaVac vaccine was associated with low reactogenicity, low immunogenicity but reduced incidence of COVID-19 among kidney transplant recipients. The lack of reduction in lethality rates is perhaps associated with the low percentage of patients developing humoral response after the second dose.

Nebulized enriched heparin to treat no critical patients with Sars-Cov-2: Triple-blind clinical trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that spreads rapidly, reaching pandemic status, causing the collapse of numerous health systems, and a strong economic and social impact. The treatment so far has not been well established and there are several clinical trials testing known drugs that have antiviral activity, due to the urgency that the global situation imposes. Drugs with specific mechanisms of action can take years to be discovered, while vaccines may also take a long time to be widely distributed while new virus variants emerge. Thus, drug repositioning has been shown to be a good strategy for defining new therapeutic approaches. Studies of the effect of enriched heparin in the replication of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in vitro assays justify the advance for clinical tests. METHODS AND ANALYSIS: A phase I/II triple-blind parallel clinical trial will be conducted. Fifty participants with radiological diagnosis of grade IIA pneumonia will be selected, which will be allocated in 2 arms. Participants allocated in Group 1 (placebo) will receive nebulized 0.9% saline. Participants allocated in Group 2 (intervention) will receive nebulized enriched heparin (2.5 mg/mL 0.9% saline). Both groups will receive the respective solutions on a 4/4 hour basis, for 7 days. The main outcomes of interest will be safety (absence of serious adverse events) and efficacy (measured by the viral load).Protocols will be filled on a daily basis, ranging from day 0 (diagnosis) until day 8.

Automatic algorithm for quantifying lung involvement in patients with chronic obstructive pulmonary disease, infection with SARS-CoV-2, paracoccidioidomycosis and no lung disease patients.

In this work, we aimed to develop an automatic algorithm for the quantification of total volume and lung impairments in four different diseases. The quantification was completely automatic based upon high resolution computed tomography exams. The algorithm was capable of measuring volume and differentiating pulmonary involvement including inflammatory process and fibrosis, emphysema, and ground-glass opacities. The algorithm classifies the percentage of each pulmonary involvement when compared to the entire lung volume. Our algorithm was applied to four different patients groups: no lung disease patients, patients diagnosed with SARS-CoV-2, patients with chronic obstructive pulmonary disease, and patients with paracoccidioidomycosis. The quantification results were compared with a semi-automatic algorithm previously validated. Results confirmed that the automatic approach has a good agreement with the semi-automatic. Bland-Altman (B&A) demonstrated a low dispersion when comparing total lung volume, and also when comparing each lung impairment individually. Linear regression adjustment achieved an R value of 0.81 when comparing total lung volume between both methods. Our approach provides a reliable quantification process for physicians, thus impairments measurements contributes to support prognostic decisions in important lung diseases including the infection of SARS-CoV-2.

Impact of nonpharmaceutical strategies on trends of COVID-19 in São Paulo State.

Interrupted time series analyses were conducted to measure the impact of social distancing policies (instituted on March 22, 2020) and of subsequent mandatory masking in the community (instituted on May 4, 2020) on the incidence and effective reproductive number of COVID-19 in São Paulo State, Brazil. Overall, the impact of social distancing both on incidence and Rt was greater than the incremental effect of mandatory masking. Those findings may reflect either a small impact of face masking or the loosening of social distancing after mandatory use of masks.

The use of health geography modeling to understand early dispersion of COVID-19 in São Paulo, Brazil.

Public health policies to contain the spread of COVID-19 rely mainly on non-pharmacological measures. Those measures, especially social distancing, are a challenge for developing countries, such as Brazil. In São Paulo, the most populous state in Brazil (45 million inhabitants), most COVID-19 cases up to April 18th were reported in the Capital and metropolitan area. However, the inner municipalities, where 20 million people live, are also at risk. As governmental authorities discuss the loosening of measures for restricting population mobility, it is urgent to analyze the routes of dispersion of COVID-19 in São Paulo territory. We hypothesize that urban hierarchy is the main responsible for the disease spreading, and we identify the hotspots and the main routes of virus movement from the metropolis to the inner state. In this ecological study, we use geographic models of population mobility to check for patterns for the spread of SARS-CoV-2 infection. We identify two patterns based on surveillance data: one by contiguous diffusion from the capital metropolitan area, and the other hierarchical with long-distance spread through major highways that connects São Paulo city with cities of regional relevance. This knowledge can provide real-time responses to support public health strategies, optimizing the use of resources in order to minimize disease impact on population and economy.

Two hundred days of COVID-19 in São Paulo State, Brazil.

Two hundred days after the first confirmed case of COVID-19 in Brazil, the epidemic has rapidly spread in metropolitan areas and advanced throughout the countryside. We followed the temporal epidemic pattern at São Paulo State, the most populous of the country, the first to have a confirmed case of COVID-19, and the one with the most significant number of cases until now. We analysed the number of new cases per day in each regional health department and calculated the effective reproduction number (Rt) over time. Social distance measures, along with improvement in testing and isolating positive cases, general population mask-wearing and standard health security protocols for essential and non-essential activities, were adopted and impacted on slowing down epidemic velocity but were insufficient to stop transmission.