LEWIS FLETCHER BUSS

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LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina

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  • article 12 Citação(ões) na Scopus
    Epidemiology of COVID-19 after Emergence of SARS-CoV-2 Gamma Variant, Brazilian Amazon, 2020-2021
    (2022) NICOLETE, Vanessa C.; RODRIGUES, Priscila T.; FERNANDES, Anderson R. J.; CORDER, Rodrigo M.; TONINI, Juliana; BUSS, Lewis F.; SALES, Flavia C.; FARIA, Nuno R.; SABINO, Ester C.; CASTRO, Marcia C.; FERREIRA, Marcelo U.
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant has been hypothesized to cause more severe illness than previous variants, especially in children. Successive SARS-CoV-2 IgG serosurveys in the Brazilian Amazon showed that agespecific attack rates and proportions of symptomatic SARS-CoV-2 infections were similar before and after Gamma variant emergence.
  • article 19 Citação(ões) na Scopus
    Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals
    (2022) BRIZZI, Andrea; WHITTAKER, Charles; SERVO, Luciana M. S.; HAWRYLUK, Iwona; JR, Carlos A. Prete; SOUZA, William M. de; AGUIAR, Renato S.; ARAUJO, Leonardo J. T.; BASTOS, Leonardo S.; BLENKINSOP, Alexandra; BUSS, Lewis F.; CANDIDO, Darlan; CASTRO, Marcia C.; COSTA, Silvia F.; CRODA, Julio; SANTOS, Andreza Aruska de Souza; DYE, Christopher; FLAXMAN, Seth; FONSECA, Paula L. C.; GEDDES, Victor E. V.; GUTIERREZ, Bernardo; LEMEY, Philippe; LEVIN, Anna S.; MELLAN, Thomas; BONFIM, Diego M.; MISCOURIDOU, Xenia; MISHRA, Swapnil; MONOD, Melodie; MOREIRA, Filipe R. R.; NELSON, Bruce; PEREIRA, Rafael H. M.; RANZANI, Otavio; SCHNEKENBERG, Ricardo P.; SEMENOVA, Elizaveta; SONNABEND, Raphael; SOUZA, Renan P.; XI, Xiaoyue; SABINO, Ester C.; FARIA, Nuno R.; BHATT, Samir; RATMANN, Oliver
    Analysis of individual-level patient records from Brazil reveals that the extensive shocks in COVID-19 mortality rates are associated with pre-pandemic geographic inequities as well as shortages in healthcare capacity during the pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.
  • article 213 Citação(ões) na Scopus
    Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil
    (2020) SOUZA, William Marciel de; BUSS, Lewis Fletcher; CANDIDO, Darlan da Silva; CARRERA, Jean-Paul; LI, Sabrina; ZAREBSKI, Alexander E.; PEREIRA, Rafael Henrique Moraes; PRETE JR., Carlos A.; SOUZA-SANTOS, Andreza Aruska de; PARAG, Kris V.; BELOTTI, Maria Carolina T. D.; VINCENTI-GONZALEZ, Maria F.; MESSINA, Janey; SALES, Flavia Cristina da Silva; ANDRADE, Pamela dos Santos; NASCIMENTO, Vitor Heloiz; GHILARDI, Fabio; ABADE, Leandro; GUTIERREZ, Bernardo; KRAEMER, Moritz U. G.; BRAGA, Carlos K. V.; AGUIAR, Renato Santana; ALEXANDER, Neal; MAYAUD, Philippe; BRADY, Oliver J.; MARCILIO, Izabel; GOUVEIA, Nelson; LI, Guangdi; TAMI, Adriana; OLIVEIRA, Silvano Barbosa de; PORTO, Victor Bertollo Gomes; GANEM, Fabiana; ALMEIDA, Walquiria Aparecida Ferreira de; FANTINATO, Francieli Fontana Sutile Tardetti; MACARIO, Eduardo Marques; OLIVEIRA, Wanderson Kleber de; NOGUEIRA, Mauricio L.; PYBUS, Oliver G.; WU, Chieh-Hsi; CRODA, Julio; SABINO, Ester C.; FARIA, Nuno Rodrigues
    Brazil has one of the fastest-growing COVID-19 epidemics in the world. De Souza et al. report epidemiological, demographic and clinical findings for COVID-19 cases in the country during the first 3 months of the epidemic. The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. TheR(0)value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.
  • article 289 Citação(ões) na Scopus
    Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic
    (2021) BUSS, Lewis F.; JR, Carlos A. Prete; ABRAHIM, Claudia M. M.; JR, Alfredo Mendrone; SALOMON, Tassila; ALMEIDA-NETO, Cesar de; FRANCA, Rafael F. O.; BELOTTI, Maria C.; CARVALHO, Maria P. S. S.; COSTA, Allyson G.; CRISPIM, Myuki A. E.; FERREIRA, Suzete C.; FRAIJI, Nelson A.; GURZENDA, Susie; WHITTAKER, Charles; KAMAURA, Leonardo T.; TAKECIAN, Pedro L.; PEIXOTO, Pedro da Silva; OIKAWA, Marcio K.; NISHIYA, Anna S.; ROCHA, Vanderson; SALLES, Nanci A.; SANTOS, Andreza Aruska de Souza; SILVA, Martirene A. da; CUSTER, Brian; V, Kris Parag; BARRAL-NETTO, Manoel; KRAEMER, Moritz U. G.; PEREIRA, Rafael H. M.; PYBUS, Oliver G.; BUSCH, Michael P.; CASTRO, Marcia C.; DYE, Christopher; NASCIMENTO, Vitor H.; FARIA, Nuno R.; SABINO, Ester C.
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in Manaus, the capital of Amazonas state in northern Brazil. The attack rate there is an estimate of the final size of the largely unmitigated epidemic that occurred in Manaus. We use a convenience sample of blood donors to show that by June 2020, 1 month after the epidemic peak in Manaus, 44% of the population had detectable immunoglobulin G (IgG) antibodies. Correcting for cases without a detectable antibody response and for antibody waning, we estimate a 66% attack rate in June, rising to 76% in October. This is higher than in Sao Paulo, in southeastern Brazil, where the estimated attack rate in October was 29%. These results confirm that when poorly controlled, COVID-19 can infect a large proportion of the population, causing high mortality.
  • article 0 Citação(ões) na Scopus
    SARS-CoV-2 seropositivity and COVID-19 among 5 years-old Amazonian children and their association with poverty and food insecurity
    (2022) FERREIRA, Marcelo U.; GIACOMINI, Isabel; SATO, Priscila M.; LOURENCO, Barbara H.; NICOLETE, Vanessa C.; BUSS, Lewis F.; MATIJASEVICH, Alicia; CASTRO, Marcia C.; CARDOSO, Marly A.
    Background The epidemiology of childhood SARS-CoV-2 infection and COVID-19-related illness remains little studied in high-transmission tropical settings, partly due to the less severe clinical manifestations typically developed by children and the limited availability of diagnostic tests. To address this knowledge gap, we investigate the prevalence and predictors of SARS-CoV-2 infection (either symptomatic or not) and disease in 5 years-old Amazonian children. Methodology/Principal findings We retrospectively estimated SARS-CoV-2 attack rates and the proportion of infections leading to COVID-19-related illness among 660 participants in a population-based birth cohort study in the Jurua ' Valley, Amazonian Brazil. Children were physically examined, tested for SARS-CoV-2 IgG and IgM antibodies, and had a comprehensive health questionnaire administered during a follow-up visit at the age of 5 years carried out in January or June-July 2021. We found serological evidence of past SARS-CoV-2 infection in 297 (45.0%; 95% confidence interval [CI], 41.2-48.9%) of 660 cohort participants, but only 15 (5.1%; 95% CI, 2.9-8.2%) seropositive children had a prior medical diagnosis of COVID-19 reported by their mothers or guardians. The period prevalence of clinically apparent COVID19, defined as the presence of specific antibodies plus one or more clinical symptoms suggestive of COVID-19 (cough, shortness of breath, and loss of taste or smell) reported by their mothers or guardians since the pandemic onset, was estimated at 7.3% (95% CI, 5.4-9.5%). Importantly, children from the poorest households and those with less educated mothers were significantly more likely to be seropositive, after controlling for potential confounders by mixed-effects multiple Poisson regression analysis. Likewise, the period prevalence of COVID-19 was 1.8-fold (95%, CI 1.2-2.6-fold) higher among cohort participants exposed to food insecurity and 3.0-fold (95% CI, 2.8-3.5-fold) higher among those born to non-White mothers. Finally, children exposed to household and family contacts who had COVID-19 were at an increased risk of being SARS-CoV-2 seropositive and-even more markedly-of having had clinically apparent COVID-19 by the age of 5 years. Conclusions/Significance Childhood SARS-CoV-2 infection and COVID-19-associated illness are substantially under-diagnosed and underreported in the Amazon. Children in the most socioeconomically vulnerable households are disproportionately affected by SARS-CoV-2 infection and disease. Author summary The epidemiology of childhood COVID-19 in the tropics remains a relatively neglected research topic, in part because SARS-CoV-2 typically causes fewer severe illnesses, hospitalizations, and deaths in children than in adults. Here we show that 45% of 660 participants in a birth cohort study in the Brazilian Amazon had SARS-CoV-2 antibodies at the age of 5 years, although only 5% of them reported previously diagnosed COVID-19 episodes-implying that as many as 8 in 9 SARS-CoV-2 infections had remained undiagnosed in these young children. Only 16% of the seropositive children had reportedly experienced cough, shortness of breath, and/or loss of taste or smell. The most socioeconomically vulnerable participants were more likely to have experienced SARS-CoV-2 infection and overt COVID-19 by the age of 5 years. Importantly, children exposed to household food insecurity, which affects 54% of our study participants, had their COVID-19 risk increased by 76%.
  • article 18 Citação(ões) na Scopus
    Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals
    (2021) NUNES, Maria Carmo P.; BUSS, Lewis F.; SILVA, Jose Luiz P.; MARTINS, Larissa Natany A.; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; BRITO, Bruno Oliveira de Figueiredo; FERREIRA, Ariela Mota; OLIVEIRA, Lea Campos; BIERRENBACH, Ana Luiza; FERNANDES, Fabio; BUSCH, Michael P.; HOTTA, Viviane Tiemi; MARTINELLI, Luiz Mario Baptista; SOEIRO, Maria Carolina F. Almeida; BRENTEGANI, Adriana; SALEMI, Vera M. C.; MENEZES, Marcia M.; RIBEIRO, Antonio Luiz P.; SABINO, Ester Cerdeira
    Background: There are few contemporary cohorts of Trypanosoma cruzi-seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. Methods: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi-seropositive blood donors. T. cruzi-seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration 120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. Results: We enrolled 499 T. cruzi-seropositive donors (age 4810 years, 52% male), 488 T. cruzi-seronegative donors (age 49 +/- 10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48 +/- 8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in T. cruzi-seropositive donors with cardiomyopathy at baseline. Among T. cruzi-seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from T. cruzi-seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi-seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]). Conclusions: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti-T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.
  • article 1 Citação(ões) na Scopus
    Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole
    (2021) FRANCO, Lucas A. M.; MOREIRA, Carlos H. V.; BUSS, Lewis F.; OLIVEIRA, Lea C.; MARTINS, Roberta C. R.; MANULI, Erika R.; LINDOSO, Jose A. L.; BUSCH, Michael P.; PEREIRA, Alexandre C.; SABINO, Ester C.
    Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. Methods: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. Results: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 x 10(-8)). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. Conclusions: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment.
  • article 11 Citação(ões) na Scopus
    Declining antibody levels to Trypanosoma cruzi correlate with polymerase chain reaction positivity and electrocardiographic changes in a retrospective cohort of untreated Brazilian blood donors
    (2020) BUSS, Lewis F.; SILVA, Lea Campos de Oliveira-da; MOREIRA, Carlos H. V.; MANULI, Erika R.; SALES, Flavia C.; MORALES, Ingra; GERMANIO, Clara Di; ALMEIDA-NETO, Cesar de; BAKKOUR, Sonia; CONSTABLE, Paul; PINTO-FILHO, Marcelo M.; RIBEIRO, Antonio L.; BUSCH, Michael; SABINO, Ester C.
    Author summary Infection with the single-celled parasite Trypanosoma cruzi (Chagas disease) is thought to be lifelong. However, only a third of infected people develop Chagas cardiomyopathy-the main disease manifestation. This may reflect the different extent to which individuals control the parasite, with some potentially clearing it entirely. In chronically infected immunocompetent patients, a marker of parasite burden is the quantity of antibody against T. cruzi in the blood: more parasite, more immune stimulation, more antibody. In this study we show how antibody levels change over many years in a cohort of untreated patients with Chagas disease. We find that among individuals with falling or low/borderline antibody levels there was a lower rate of parasite detection in the blood and a lower rate of cardiomyopathy. 60% of subjects with falling antibody levels had no evidence of active disease, twice as many as among patients with other antibody trajectories (stable or rising). Our findings support an account of the natural history of Chagas disease in which a proportion of those infected achieve a greater control of the parasite, with some individuals potentially clearing it completely. Background Although infection with Trypanosoma cruzi is thought to be lifelong, less than half of those infected develop cardiomyopathy, suggesting greater parasite control or even clearance. Antibody levels appear to correlate with T. cruzi (antigen) load. We test the association between a downwards antibody trajectory, PCR positivity and ECG alterations in untreated individuals with Chagas disease. Methodology/Principal findings This is a retrospective cohort of T. cruzi seropositive blood donors. Paired blood samples (index donation and follow-up) were tested using the VITROS Immunodiagnostic Products Anti-T.cruzi (Chagas) assay (Ortho Clinical Diagnostics, Raritan NJ) and PCR performed on the follow-up sample. A 12-lead resting ECG was performed. Significant antibody decline was defined as a reduction of > 1 signal-to-cutoff (S/CO) unit on the VITROS assay. Follow-up S/CO of < 4 was defined as borderline/low. 276 untreated seropositive blood donors were included. The median (IQR) follow-up was 12.7 years (8.5-16.9). 56 (22.1%) subjects had a significant antibody decline and 35 (12.7%) had a low/borderline follow-up result. PCR positivity was lower in the falling (26.8% vs 52.8%, p = 0.001) and low/borderline (17.1% vs 51.9%, p < 0.001) antibody groups, as was the rate of ECG abnormalities. Falling and low/borderline antibody groups were predominantly composed of individuals with negative PCR and normal ECG findings: 64% and 71%, respectively. Conclusions/Significance Low and falling antibody levels define a phenotype of possible spontaneous parasite clearance.
  • article 15 Citação(ões) na Scopus
    Comparison of FDA accelerated vs regular pathway approvals for lung cancer treatments between 2006 and 2018
    (2020) RIBEIRO, Tatiane Bomfim; BUSS, Lewis; WAYANT, Cole; NOBRE, Moacyr Roberto Cuce
    Regulatory agencies around the world have been using flexible requirements for approval of new drugs, especially for cancer drugs. The US Food and Drug Administration (FDA) is mostly the first agency to approve new drugs worldwide, mainly due to the faster terms of the accelerated pathway and breakthrough therapy designation. Surrogate endpoints and preliminary data (e.g. single-arm and phase 2 studies) are used for these new approvals, however larger effect sizes are expected. We aim to compare FDA Accelerated vs Regular Pathway approvals and Breakthrough therapy designations (BTD) for lung cancer treatments between 2006 and 2018 regarding study design, sample size, outcome measures and effect size. We assessed the FDA database to collect data from studies that formed the basis of approvals of new drugs or indications for lung cancer spanning from 2006 to 2018. We found that accelerated pathway approvals are based on significantly more single-arm studies with small sample sizes and surrogate primary endpoints. However, effect size was not different between the pathways. A large proportion of studies used to support regular pathway approvals also showed these characteristics that are related to low quality and uncertain evidence. Compared to other approvals, BTD were more frequently based on single-arm studies. There was no significant difference in use of surrogate endpoints or sample size. 44% of BTD were based on studies demonstrating large effect sizes, proportionally more than approvals not receiving this designation. In conclusion, based on the indicators of evidence quality we extracted, criteria's for granting accelerated approval and breakthrough therapy designation seen not clear. Faster approvals are in the majority full of uncertainties which should be viewed with caution and the patient have to be communicated to allow shared decision making. Post-marketing validation is essential.
  • article 10 Citação(ões) na Scopus
    Reinfection by the SARS-CoV-2 Gamma variant in blood donors in Manaus, Brazil
    (2022) PRETE JR., Carlos A.; BUSS, Lewis F.; BUCCHERI, Renata; ABRAHIM, Claudia M. M.; SALOMON, Tassila; CRISPIM, Myuki A. E.; OIKAWA, Marcio K.; GREBE, Eduard; COSTA, Allyson G. da; FRAIJI, Nelson A.; CARVALHO, Maria do P. S. S.; WHITTAKER, Charles; ALEXANDER, Neal; FARIA, Nuno R.; DYE, Christopher; NASCIMENTO, Vitor H.; BUSCH, Michael P.; SABINO, Ester Cerdeira
    Background The city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection. Methods We tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants. Results From 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0-24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3-34.2%) and 39.3% (95% CI 29.5-50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3-92.7%), decreasing to respectively 72.5% (95% CI 54.7-83.6%) and 39.5% (95% CI 14.1-57.8%) if probable and possible reinfections are included. Conclusions Reinfection by Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.