Validation of the questionnaire of olfactory disorders (QOD) for the Brazilian population.

BACKGROUND: The incidence of olfactory disorders has increased in recent years, mainly related to COVID-19 infection. In Brazil, over 37 million cases of COVID-19 have been reported, and approximately 10 % of those cases continue to experience olfactory disorders for more than one month. Despite the significant negative impact on well-being, there is currently no validated instrument to assess how olfactory disorders impact the quality of life in Brazil. OBJECTIVES: This study aimed to validate the Questionnaire of Olfactory Disorders (QOD) for Brazilian Portuguese. METHODS: The authors first performed translation, back-translation, expert review, pre-testing, psychometric evaluation and cultural adaptation of the English version of the questionnaire. To assure linguistic and conceptual equivalence of the translated questionnaire, 126 participants from two Brazilian states and varying degrees of olfactory loss answered the QOD and the World Health Organization Quality of Life bref (WHOQOL-bref) questionnaires. The University of Pennsylvania Smell Identification Test (UPSIT®) was used to quantify the olfactory loss. Furthermore, to evaluate the reliability of the Portuguese version a test-retest was performed on a subgroup of patients. The authors observed a high Cronbach's alpha (α = 0.86) for internal consistency of the quality of Life (QOD-QOL) statements. FINDINGS: As expected, there was a negative correlation between QOD-QOL and UPSIT® (Spearman's ρ = -0.275, p = 0.002), since QOL score increases and UPSIT® score decreases with worsening of olfactory function. Correlations were moderate between QOD-QOL and WHOQOL-bref mean (Spearman's ρ = -0.374, p < 0.001) and weak to moderate between the QOD-QOL and Visual Analog Scale of the QOD regarding professional life, leisure, and private life (Spearman's ρ = -0.316, p = 0.000; Spearman's ρ = -0.293, p = 0.001; Spearman's ρ = -0.261, p = 0.004; respectively). CONCLUSION: In conclusion, the authors have demonstrated a high internal consistency and validity of the Brazilian Portuguese version of the QOD for evaluating the quality of life in individuals with olfactory disorders.

Pathophysiology of chikungunya virus infection associated with fatal outcomes.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.

Risk of death following chikungunya virus disease in the 100 Million Brazilian Cohort, 2015-18: a matched cohort study and self-controlled case series.

BACKGROUND: Chikungunya virus outbreaks have been associated with excess deaths at the ecological level. Previous studies have assessed the risk factors for severe versus mild chikungunya virus disease. However, the risk of death following chikungunya virus disease compared with the risk of death in individuals without the disease remains unexplored. We aimed to investigate the risk of death in the 2 years following chikungunya virus disease. METHODS: We used a population-based cohort study and a self-controlled case series to estimate mortality risks associated with chikungunya virus disease between Jan 1, 2015, and Dec 31, 2018, in Brazil. The dataset was created by linking national databases for social programmes, notifiable diseases, and mortality. For the matched cohort design, individuals with chikungunya virus disease recorded between Jan 1, 2015, and Dec 31, 2018, were considered as exposed and those who were arbovirus disease-free and alive during the study period were considered as unexposed. For the self-controlled case series, we included all deaths from individuals with a chikungunya virus disease record, and each individual acted as their own control according to different study periods relative to the date of disease. The primary outcome was all-cause natural mortality up to 728 days after onset of chikungunya virus disease symptoms, and secondary outcomes were cause-specific deaths, including ischaemic heart diseases, diabetes, and cerebrovascular diseases. FINDINGS: In the matched cohort study, we included 143 787 individuals with chikungunya virus disease who were matched, at the day of symptom onset, to unexposed individuals using sociodemographic factors. The incidence rate ratio (IRR) of death within 7 days of chikungunya symptom onset was 8·40 (95% CI 4·83-20·09) as compared with the unexposed group and decreased to 2·26 (1·50-3·77) at 57-84 days and 1·05 (0·82-1·35) at 85-168 days, with IRR close to 1 and wide CI in the subsequent periods. For the secondary outcomes, the IRR of deaths within 28 days after disease onset were: 1·80 (0·58-7·00) for cerebrovascular diseases, 3·75 (1·33-17·00) for diabetes, and 3·67 (1·25-14·00) for ischaemic heart disease, and there was no evidence of increased risk in the subsequent periods. For the self-controlled case series study, 1933 individuals died after having had chikungunya virus disease and were included in the analysis. The IRR of all-cause natural death within 7 days of symptom onset of chikungunya virus disease was 8·75 (7·18-10·66) and decreased to 1·59 (1·26-2·00) at 57-84 days and 1·09 (0·92-1·29) at 85-168 days. For the secondary outcomes, the IRRs of deaths within 28 days after disease onset were: 2·73 (1·50-4·96) for cerebrovascular diseases, 8·43 (5·00-14·21) for diabetes, and 2·38 (1·33-4·26) for ischaemic heart disease, and there was no evidence of increased risk at 85-168 days. INTERPRETATION: Chikungunya virus disease is associated with an increased risk of death for up to 84 days after symptom onset, including deaths from cerebrovascular diseases, ischaemic heart diseases, and diabetes. This study highlights the need for equitable access to approved vaccines and effective anti-chikungunya virus therapeutics and reinforces the importance of robust vector-control efforts to reduce viral transmission. FUNDING: Brazilian National Research Council (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia, Wellcome Trust, and UK Medical Research Council. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).

Chikungunya virus antepartum transmission and abnormal infant outcomes in a cohort of pregnant women in Nigeria.

OBJECTIVES: Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. METHODS: Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV. RESULTS: Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions. CONCLUSION: In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.

Early detection of respiratory disease outbreaks through primary healthcare data.

Background: The emergence of coronavirus disease 2019 (COVID-19) in 2020 highlighted the relevance of surveillance systems in detecting early signs of potential outbreaks, thus enabling public health authorities to act before the pathogen becomes widespread. Syndromic digital surveillance through web applications has played a crucial role in monitoring the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. However, this approach requires expensive infrastructure, which is not available in developing countries. Pre-existing sources of information, such as encounters in primary health care (PHC), can provide valuable data for a syndromic surveillance system. Here we evaluated the utility of PHC data to identify early warning signals of the first COVID-19 outbreak in Bahia-Brazil in 2020. Methods: We compared the weekly counts of PHC encounters due to respiratory complaints and the number of COVID-19 cases in 2020 in Bahia State - Brazil. We used the data from December 2016 to December 2019 to predict the expected number of encounters in 2020. We analysed data aggregated by geographic regions (n = 34) and included those where historical PHC data was available for at least 70% of the population. Results: Twenty-one out of 34 regions met the inclusion criteria. We observed that notification of COVID-19 cases was preceded by at least two weeks with an excess of encounters of respiratory complaints in 18/21 (86%) of the regions analysed and four weeks or more in 10/21 (48%) regions. Conclusions: Digital syndromic surveillance systems based on already established PHC databases may add time to preparedness and response to emerging epidemics.

Safety of BNT162b2 and CoronaVac during pregnancy on birth outcomes and neonatal mortality: a cohort study from Brazil.

BACKGROUND: COVID-19 vaccines have been shown to protect pregnant individuals against mild and severe COVID-19 outcomes. However, limited safety data are available for inactivated (CoronaVac) and mRNA (BNT162b2) vaccines during pregnancy regarding their effect on birth outcomes and neonatal mortality, especially in low- and middle-income countries. METHODS: We conducted a retrospective population-based cohort study in Rio de Janeiro, Brazil, with 17 513 singleton live births conceived between 15 May 2021 and 23 October 2021. The primary exposure was maternal vaccination with CoronaVac or mRNA BNT162b2 vaccines and sub-analyses were performed by the gestational trimester of the first dose and the number of doses given during pregnancy. The outcomes were pre-term birth (PTB), small for gestational age (SGA), low birthweight (LBW), low Apgar 5 and neonatal death. We used the Cox model to estimate the hazard ratio (HR) with a 95% CI and applied the inverse probability of treatment weights to generate adjusted HRs. RESULTS: We found no significant increase in the risk of PTB (HR: 0.98; 95% CI 0.88, 1.10), SGA (HR: 1.09; 95% CI 0.96, 1.27), LBW (HR: 1.00; 95% CI 0.88, 1.14), low Apgar 5 (HR: 0.81; 95% CI 0.55, 1.22) or neonatal death (HR: 0.88; 95% CI 0.56, 1.48) in women vaccinated with CoronaVac or BNT162b2 vaccines. These findings were consistent across sub-analyses stratified by the gestational trimester of the first dose and the number of doses given during pregnancy. We found mild yet consistent protection against PTB in women who received different vaccine platforms during the third trimester of pregnancy (any vaccines, HR: 0.78; 95% CI 0.63, 0.98; BNT162b2, HR: 0.75; 95% CI 0.59, 0.99). CONCLUSIONS: This study provides evidence that COVID-19 vaccination in all trimesters of pregnancy, irrespective of the vaccine type, is safe and does not increase the risk of adverse birth outcomes or neonatal deaths.

Transcriptome Analysis Identifies the Crosstalk between Dendritic and Natural Killer Cells in Human Cutaneous Leishmaniasis.

Skin ulcers of cutaneous leishmaniasis (CL) are characterized by a localized inflammatory response mediated by innate and adaptive immune cells, including dendritic cells (DC) and natural killer (NK) cells. Bidirectional interactions between DCs and NK cells contribute to tailor leishmaniasis outcome. Despite advances in the Leishmania biology field in recent decades, the mechanisms involved in DC/NK-mediated control of Leishmania sp. pathogenesis as well as the cellular and molecular players involved in such interaction remain unclear. The present study sought to investigate canonical pathways associated with CL arising from Leishmania braziliensis infection. Initially, two publicly available microarray datasets of skin biopsies from active CL lesions were analyzed, and five pathways were identified using differentially expressed genes. The "Crosstalk between DCs and NK cells" pathway was notable due to a high number of modulated genes. The molecules significantly involved in this pathway were identified, and our findings were validated in newly obtained CL biopsies. We found increased expression of TLR4, TNFRSF1B, IL-15, IL-6, CD40, CCR7, TNF and IFNG, confirming the analysis of publicly available datasets. These findings reveal the "crosstalk between DCs and NK cells" as a potential pathway to be further explored in the pathogenesis of CL, especially the expression of CCR7, which is correlated with lesion development.

Chikungunya virus antepartum transmission and abnormal infant outcomes in Nigeria.

Chikungunya virus (CHIKV) has become a global public health concern since the reemergence of the Indian Ocean lineage and expansion of the Asian genotype. CHIKV infection causes acute febrile illness, rash, and arthralgia and during pregnancy may affect both mothers and infants. The mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. We screened 1006 pregnant women at two clinics in Nigeria between 2019 and 2022 and investigated the prevalence and MTCT of CHIKV. Of the 1006, 119 tested positive for CHIKV IgM, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with 8 normal and 4 abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis and jaundice. CHIKV IgM testing identified 3 antepartum transmissions, further studies will determine its impact in antepartum infection.

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil.

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

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.

Analyses of Early ZIKV Genomes Are Consistent with Viral Spread from Northeast Brazil to the Americas.

The Americas, particularly Brazil, were greatly impacted by the widespread Zika virus (ZIKV) outbreak in 2015 and 2016. Efforts were made to implement genomic surveillance of ZIKV as part of the public health responses. The accuracy of spatiotemporal reconstructions of the epidemic spread relies on the unbiased sampling of the transmission process. In the early stages of the outbreak, we recruited patients exhibiting clinical symptoms of arbovirus-like infection from Salvador and Campo Formoso, Bahia, in Northeast Brazil. Between May 2015 and June 2016, we identified 21 cases of acute ZIKV infection and subsequently recovered 14 near full-length sequences using the amplicon tiling multiplex approach with nanopore sequencing. We performed a time-calibrated discrete phylogeographic analysis to trace the spread and migration history of the ZIKV. Our phylogenetic analysis supports a consistent relationship between ZIKV migration from Northeast to Southeast Brazil and its subsequent dissemination beyond Brazil. Additionally, our analysis provides insights into the migration of ZIKV from Brazil to Haiti and the role Brazil played in the spread of ZIKV to other countries, such as Singapore, the USA, and the Dominican Republic. The data generated by this study enhances our understanding of ZIKV dynamics and supports the existing knowledge, which can aid in future surveillance efforts against the virus.

Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group.

Background: There is limited data on the prevalence and risk factors for long COVID and few prospective studies with appropriate control groups and adequate sample sizes. We performed a prospective study to determine the prevalence and risk factors for long COVID. Methods: We recruited individuals aged ≥15 years who were clinically suspected of having an acute SARS-CoV-2 infection from September 2020 to April 2021. We collected nasopharyngeal swabs three to five days following symptom onset for analysing using reverse transcriptase polymerase chain reaction (RT-PCR). We also collected clinical and sociodemographic characteristics from both SARS-CoV-2 positive and negative participants using structured questionnaires. We followed-up the participants via telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life. Results: We followed 814 participants (412 COVID-19 positive and 402 COVID-19 negative persons). Most (n = 741/814) had mild symptoms. Both groups had similar sociodemographic and clinical characteristics, except for the hospitalization rate (15.8% in the COVID-19 positive vs 1.5% in the COVID-19 negative group). One month after disease onset, 122/412 (29.6%) individuals in the COVID-19 positive (long COVID) and 24 (6%) in the COVID-19 negative group reported residual symptoms. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms in the acute phase. Compared to recovered individuals, older age and having more than five symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID, with 57 (55.9%) reporting an impact in at least one dimension of the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) questionnaire. Conclusions: In this prospective study consisting predominantly of individuals with mild disease, the persistence of symptoms after an acute respiratory illness was associated with a diagnosis of COVID-19. Polysymptomatic acute disease and older age were risk factors for long COVID.

Syndromic Surveillance Using Structured Telehealth Data: Case Study of the First Wave of COVID-19 in Brazil.

BACKGROUND: Telehealth has been widely used for new case detection and telemonitoring during the COVID-19 pandemic. It safely provides access to health care services and expands assistance to remote, rural areas and underserved communities in situations of shortage of specialized health professionals. Qualified data are systematically collected by health care workers containing information on suspected cases and can be used as a proxy of disease spread for surveillance purposes. However, the use of this approach for syndromic surveillance has yet to be explored. Besides, the mathematical modeling of epidemics is a well-established field that has been successfully used for tracking the spread of SARS-CoV-2 infection, supporting the decision-making process on diverse aspects of public health response to the COVID-19 pandemic. The response of the current models depends on the quality of input data, particularly the transmission rate, initial conditions, and other parameters present in compartmental models. Telehealth systems may feed numerical models developed to model virus spread in a specific region. OBJECTIVE: Herein, we evaluated whether a high-quality data set obtained from a state-based telehealth service could be used to forecast the geographical spread of new cases of COVID-19 and to feed computational models of disease spread. METHODS: We analyzed structured data obtained from a statewide toll-free telehealth service during 4 months following the first notification of COVID-19 in the Bahia state, Brazil. Structured data were collected during teletriage by a health team of medical students supervised by physicians. Data were registered in a responsive web application for planning and surveillance purposes. The data set was designed to quickly identify users, city, residence neighborhood, date, sex, age, and COVID-19-like symptoms. We performed a temporal-spatial comparison of calls reporting COVID-19-like symptoms and notification of COVID-19 cases. The number of calls was used as a proxy of exposed individuals to feed a mathematical model called "susceptible, exposed, infected, recovered, deceased." RESULTS: For 181 (43%) out of 417 municipalities of Bahia, the first call to the telehealth service reporting COVID-19-like symptoms preceded the first notification of the disease. The calls preceded, on average, 30 days of the notification of COVID-19 in the municipalities of the state of Bahia, Brazil. Additionally, data obtained by the telehealth service were used to effectively reproduce the spread of COVID-19 in Salvador, the capital of the state, using the "susceptible, exposed, infected, recovered, deceased" model to simulate the spatiotemporal spread of the disease. CONCLUSIONS: Data from telehealth services confer high effectiveness in anticipating new waves of COVID-19 and may help understand the epidemic dynamics.

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

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

The health facility as a risk factor for multidrug-resistant gram-negative bacteria in critically ill patients with COVID-19.

BACKGROUND: The relationship between Multidrug Resistant-Gram Negative Bacteria (MDR-GNB) infection and colonization in critically ill COVID-19 patients has been observed, however, it is still poorly understood. This study evaluated the risk factors for acquiring MDR-GNB in patients with severe COVID-19 in Intensive Care Units (ICU). METHODS: This is a nested case-control study in a cohort of 400 adult patients (≥ 18 years old) with COVID-19, hospitalized in the ICU of 4 hospitals in the city of Curitiba, Brazil. Cases were critical COVID-19 patients with one or more MDR GNB from any surveillance and/or clinical cultures were taken during their ICU stay. Controls were patients from the same units with negative cultures for MDR-GNB. Bivariate and multivariate analyses were done. RESULTS: Sixty-seven cases and 143 controls were included. Independent risk factors for MDR bacteria were: male gender (OR = 2.6; 95% CI 1.28‒5.33; p = 0.008); the hospital of admission (OR = 3.24; 95% CI 1.39‒7.57; p = 0.006); mechanical ventilation (OR = 25.7; 95% CI 7.26‒91; p < 0.0001); and desaturation on admission (OR = 2.6; 95% CI 1.27‒5.74; p = 0.009). CONCLUSIONS: Male gender, desaturation, mechanical ventilation, and the hospital of admission were the independent factors associated with MDR-GNB in patients in the ICU with COVID-19. The only modifiable factor was the hospital of admission, where a newly opened hospital posed a higher risk. Therefore, coordinated actions toward a better quality of care for critically ill COVID-19 patients are essential.

Metabolic disorders and post-acute hospitalization in black/mixed-race patients with long COVID in Brazil: A cross-sectional analysis.

BACKGROUND: Although low-middle income countries have been disproportionately affected by the COVID-19 pandemic, there is scarce information about the impact of long COVID on their population. This study aimed to evaluate long COVID symptomatology, complications (hospital readmission and metabolic disorders), and main clinical features that impact Quality of Life (QoL). METHODS: This cross-sectional study provides a detailed clinical and laboratory picture of individuals who presented residual symptoms after mild to severe acute COVID-19. Between Aug-2020 to Sep-2021, long COVID patients were evaluated in a reference center for long COVID in Bahia State, Brazil. The EQ-5D-5L questionnaire accessed QoL. RESULTS: A total of 1164 (52 ±13.4 years, 57% female, 88% black/mixed-race) were evaluated 2.3 [IQR = 1.6-3.7] months after mild (n = 351, 30.2%), moderate (338, 29.0%) or severe (475, 40.8%) acute illness. Dyspnea (790, 67.9%), fatigue (738, 63.5%), and chest pain (525, 42.9%) were the most frequent residual symptoms regardless of acute severity, affecting the QoL of 88.9% of patients (n/N-826/925), mainly the domains of anxiety/depression and pain/discomfort. High levels of HbA1c were detected for 175 out of 664 patients (26.6%), 40% of them without a previous diagnosis of diabetes mellitus. Of note, hospital admission one-to-three months after the acute phase of disease was required for 51 (4.4%) patients. CONCLUSION: In this majority-black/mixed-race population, long COVID was associated with post-acute hospitalization, newly diagnosed diabetes mellitus, and decreased QoL, particularly in women and regardless of disease severity of acute infection, suggesting important implications for health care system.