ABSTRACT In Brazil, the COVID-19 burden was substantial, and risk factors associated with higher in-hospital mortality rates have been extensively studied. However, information on short-term all-cause mortality and the factors associated with death in patients who survived the hospitalization period of acute SARS-CoV-2 infection is limited. We analyzed the six-month post-hospitalization mortality rate and possible risk factors of COVID-19 patients in a single center in Brazil. This is a retrospective cohort study focused on a six-month follow-up. The exclusion criteria were death during hospitalization, transference to another hospital, and age under 18. We collected data from the charts of all hospitalized patients from March 2020 to December 2020 with a positive RT-PCR test for SARS-CoV-2, resulting in a sample size of 106 patients. The main outcome was death after hospitalization, whereas comorbidities and demographics were evaluated as risk factors. The crude post-hospitalization death rate was 16%. The first 30 days of follow-up had the highest mortality rate. In a Cox regression model for post-hospitalization mortality, previous chronic kidney disease (HR, 4.06, 95%CI 1.46 – 11.30) and longer hospital stay (HR 1.01, 95%CI 1.00 – 1.02) were the only factors statistically associated with death. In conclusion, a high six-month all-cause mortality was observed. Within the six-month follow-up, a higher risk of death was observed for patients who had prior CKD and longer hospital stay. These findings highlight the importance of more intensive medical surveillance during this period.

Mental disorders such as anxiety, depression, and memory loss have been described in patients with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Social, psychological, and biological stressors may take part in these processes. There is a consensus on the recognition of an acute nervous form of CD. In chronic CD patients, a neurological form is associated with immunosuppression and neurobehavioural changes as sequelae of stroke. The chronic nervous form of CD has been refuted, based on the absence of histopathological lesions and neuroinflammation; however, computed tomography shows brain atrophy. Overall, in preclinical models of chronic T. cruzi infection in the absence of neuroinflammation, behavioural disorders such as anxiety and depression, and memory loss are related to brain atrophy, parasite persistence, oxidative stress, and cytokine production in the central nervous system. Interferon-gamma (IFNγ)-bearing microglial cells are colocalised with astrocytes carrying T. cruzi amastigote forms. In vitro studies suggest that IFNγ fuels astrocyte infection by T. cruzi and implicate IFNγ-stimulated infected astrocytes as sources of TNF and nitric oxide, which may also contribute to parasite persistence in the brain tissue and promote behavioural and neurocognitive changes. Preclinical trials in chronically infected mice targeting the TNF pathway or the parasite opened paths for therapeutic approaches with a beneficial impact on depression and memory loss. Despite the path taken, replicating aspects of the chronic CD and testing therapeutic schemes in preclinical models, these findings may get lost in translation as the chronic nervous form of CD does not fulfil biomedical model requirements, as the presence of neuroinflammation, to be recognised. It is hoped that brain atrophy and behavioural and neurocognitive changes are sufficient traits to bring the attention of researchers to study the biological and molecular basis of the central nervous system commitment in chronic CD.

Abstract This study aimed to evaluate the hematological and coagulation parameters according to the clinical outcomes of coronavirus disease (COVID-19). We analyzed the hematological and coagulation parameters of hospitalized patients with COVID-19 at admission, and two and three weeks during hospitalization. To assess the performance of these parameters in predicting poor outcomes, receiver operating characteristic (ROC) curves were created. We studied 128 patients with COVID-19 (59.2±17.7 years, 56% male). Non-survivors (n=54, 42%) presented significant alterations in hematological and coagulation parameters at admission, such as increased in white blood cells (WBC), neutrophil, and band cell counts, as well as elevated prothrombin time (PT), activated partial thromboplastin time, and D-dimer levels. During follow-up, the same group presented a gradual increase in D-dimer and PT levels, accompanied by a reduction in PT activity, hemoglobin, and red blood cell count (RBC). ROC curves showed that WBC, neutrophil, and band cell counts presented the best area under the curve (AUC) values with sensitivity and specificity of >70%; however, a logistic regression model combining all the parameters, except for RBC, presented an AUC of 0.89, sensitivity of 84.84%, and specificity of 77.41%. Our study shows that significant alterations in hematological and coagulation tests at admission could be useful predictors of disease severity and mortality in COVID-19.

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.

Resumo Introdução No Brasil, algumas cidades adotaram várias medidas que provavelmente tiveram um impacto positivo no controle da Covid-19. Objetivo Relatar a distribuição dos casos de Covid-19 no Brasil, no estado do Rio de Janeiro e na cidade de Niterói. Paralelamente, buscamos demonstrar as estratégias preventivas adotadas pela cidade de Niterói para o controle da Covid-19. Método Dados fornecidos pelo Ministério da Saúde e Fundação Municipal de Saúde de Niterói foram usados para relatar o número de casos e óbitos causados pela Covid-19. Para algumas análises, os dados foram agrupados por semana e normalizados para 100.000 habitantes. Resultados Até 18 de julho de 2020, o Brasil registrou 2.074.860 casos e 78.772 mortes e o estado do Rio de Janeiro registrou 135.230 casos e 11.919 mortes; ambos ainda apresentando curvas ascendentes para mortes por Covid-19. Em contrapartida, a taxa de novos óbitos/100.000 habitantes é consistentemente menor na cidade de Niterói. Estimamos que 712 mortes foram evitadas pelas medidas adotadas pela cidade de Niterói, em comparação com o que foi observado no Rio de Janeiro. Conclusão As medidas preventivas adotadas pela cidade de Niterói foram eficazes na redução tanto da disseminação do vírus quanto da taxa de óbitos. Portanto, esta discussão se mostra relevante para a tomada de decisões futuras durante o surto de Covid-19 no Brasil.

Abstract Background In Brazil, some local city government’s adopted several measures, which probably had a positive impact on COVID-19 control. Objective To report the distribution of COVID-19 cases in Brazil, Rio de Janeiro state and Niterói city. In parallel, we aimed to demonstrate the preventive strategies adopted by Niterói city. Method Data provided by the Brazilian Ministry of Health and Municipal Health Foundation of Niterói were used to report COVID-19 cases and deaths. For some analysis, data were grouped by week and normalized for 100,000 inhabitants. Results By July 18th, 2020, Brazil reported 2,074,860 cases and 78,772 deaths and Rio de Janeiro state registered 135,230 cases and 11,919 deaths; both still presenting ascendant curves for COVID-19 deaths. In contrast, the rate of new deaths per 100,000 inhabitants is consistently lower in Niterói city. Importantly, we estimated that 712 deaths were prevented by the measures adopted by Niterói city, in comparison to which was observed in Rio de Janeiro. Conclusion The early preventive measures adopted in Niterói city were effective in reducing both the viral spread and rate of deaths. In this regard, this discussion could be relevant for making future decisions during the COVID-19 outbreak in Brazil.

ABSTRACT Introduction: Some COVID-19 patients have higher mortality and the responsible factors for this unfavorable outcome is still not well understood. Objective: To study the association between ferritin levels at admission, representing an inflammatory state, and hospital mortality in COVID-19 patients. Methods: From May through July 2020, SARS-CoV-2 positive patients with moderate to severe clinical symptoms were evaluated at admission, regarding clinical and laboratory data on renal and hepatic function, hematologic parameters, cytomegalovirus co-infection, and acute phase proteins. Results: A total of 97 patients were included; mean age = 59.9 ± 16.3 years, 58.8% male, 57.7% non-white, in-hospital mortality = 45.4%. Age, ferritin, C-reactive protein, serum albumin and creatinine were significantly associated with mortality. Ferritin showed area under the curve (AUC) of 0.79 (p < 0.001) for the cut-off of 1873.0 ng/mL, sensitivity of 68.4% and specificity of 79.3% in predicting in-hospital mortality. Age ≥60 years had an odds ratio (OR) of 10.5 (95% CI = 1.8–59.5; p = 0.008) and ferritin ≥1873.0 ng/mL had an OR of 6.0 (95% CI = 1.4–26.2; p = 0.016), both independently associated with mortality based on logistic regression analysis. Conclusion: The magnitude of inflammation present at admission of COVID-19 patients, represented by high ferritin levels, is independently predictive of in-hospital mortality.

RESUMO Introdução: Estudos sugerem a associação entre a produção de anticorpos e a gravidade da coronavirus disease 2019 (Covid-19). Objetivos: Avaliar as concentrações de imunoglobulinas da classe A (IgA) e da classe G (IgG) durante a internação de pacientes com Covid-19 de acordo com o desfecho (sobrevida vs óbito). Materiais e métodos: Pacientes com infecção pela síndrome respiratória aguda grave do coronavírus 2 (Sars-CoV-2) confirmada por reação da transcriptase reversa seguida de reação em cadeia da polimerase (RT-PCR) foram incluídos neste estudo prospectivo. As amostras foram obtidas semanalmente durante o acompanhamento dos indivíduos, considerando o início dos sintomas. Os títulos de IgA e IgG anti-Sars-CoV-2 foram mensurados por meio de um imunoensaio comercial. Correlações entre IgA/IgG e valores de limiar de detecção [cycle thresholds (Ct)] para os genes alvos N1 e N2 também foram avaliadas. Resultados: Estudamos 55 pacientes com Covid-19 (59,7 ± 6,2 anos; 63,6% do sexo masculino); destes, 28 (50,9%) morreram. Observamos positividade para IgA e IgG (IgA+/IgG+) em 90,9% e 80% dos pacientes, respectivamente. A maior frequência de IgA+ foi verificada nas semanas 2 e 3, e a maior frequência de IgG+, nas semanas 3 e 4. É importante observar que os pacientes que morreram apresentaram títulos de IgA mais baixos nas primeiras duas semanas (p < 0,05); no entanto, um aumento significativo na concentração de IgA foi observado nas semanas subsequentes. Por fim, identificamos correlações significativas entre os valores de Ct e imunoglobulinas; tanto IgA quanto IgG foram correlacionadas com Ct N2 em pacientes que morreram. Conclusão: Nossos resultados sugerem que títulos mais baixos de IgA no início da Covid-19 - que estão associados a valores mais baixos de Ct - podem indicar pacientes com risco elevado de evoluir para óbito.

ABSTRACT Introduction: Studies suggest the association between antibody production and the severity of coronavirus disease 2019 (Covid-19). Objectives: To evaluate the concentrations of immunoglobulins class A (IgA) and class G (IgG) during the hospitalization period of Covid-19 patients according to the outcome (survival vs death). Materials and methods: Patients with severe acute respiratory syndrome of coronavirus 2 (Sars-CoV-2) infection confirmed by reverse transcriptase reaction followed by polymerase chain reaction (RT-PCR) were included in this prospective study. Samples were obtained weekly during the follow-up of individuals, considering symptom onset. Titers of anti-Sars-CoV-2 IgA and IgG were measured using a commercial immunoassay. Correlations between IgA/IgG and cycle threshold (Ct) values for N1 and N2 target genes were also assessed. Results: We studied 55 Covid-19 patients (59.7±16.2 years, 63.6% male), of which 28 (50.9%) died. We observed IgA and IgG positivity (IgA+ and IgG+) in 90.9% and 80% of patients, respectively. The highest IgA+ frequency was observed at weeks 2 and 3 and the highest IgG+ at weeks 3 and 4. It is important to note that patients who died presented lower IgA titers in the first two weeks (p < 0.05); however, a significant increase in IgA levels was observed in the subsequent weeks. Lastly, we identified that significant correlations between Ct values and immunoglobulins levels, both IgA and IgG were correlated with Ct N2 in patients who died. Conclusion: Our results suggest that lower IgA titers in early Covid-19, which is associated with lower Ct values, may indicate patients at higher risk for death.

RESUMEN Introducción: Los estudios sugieren una asociación entre la producción de anticuerpos y la gravedad de la enfermedad por coronavirus 2019 (Covid-19). Objetivos: Evaluar las concentraciones de inmunoglobulinas clase A (IgA) y clase G (IgG) durante la hospitalización de pacientes con Covid-19 según el desenlace (supervivencia vs muerte). Materiales y métodos: Se incluyeron en este estudio prospectivo pacientes con síndrome respiratorio agudo severo de infección por coronavirus 2 (Sars-CoV-2) confirmado por la reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR). Las muestras se obtuvieron semanalmente durante el seguimiento de los individuos, considerando la aparición de los síntomas. Los títulos de IgA e IgG anti-Sars-CoV-2 se midieron usando un inmunoensayo comercial. También se evaluaron las correlaciones entre IgA/IgG y los valores de los umbrales de ciclo [cycle threshold (Ct)] para los genes N1 y N2. Resultados: Se estudiaron 55 pacientes Covid-19 (59,7 ± 16,2 años, 63,6% varones), de los cuales 28 (50,9%) fallecieron. Observamos positividad de IgA e IgG (IgA+ e IgG+) en el 90,9% y el 80% de los pacientes, respectivamente. La frecuencia más alta de IgA+ se observó en las semanas dos y tres y la IgG + más alta en las semanas tres y cuatro. Es importante señalar que los pacientes que fallecieron presentaron títulos de IgA más bajos en las dos primeras semanas (p < 0,05); sin embargo, se observó un aumento significativo en los niveles de IgA en las semanas siguientes. Conclusión: Identificamos correlaciones significativas entre los valores de Ct y los niveles de Ig, tanto IgA como IgG se correlacionaron con Ct N2 en los pacientes que fallecieron. Nuestros resultados sugieren que los títulos de IgA más bajos en Covid-19 temprano, que se asocia con valores de Ct más bajos, pueden indicar que los pacientes tienen un mayor riesgo de muerte.

RESUMO Introdução: Diferentemente do transplante de órgãos, poucos estudos correlacionam o monitoramento da antigenemia pp65 com o diagnóstico de citomegalovírus (CMV) em pacientes com lúpus eritematoso sistêmico (LES). Objetivo: De modo a destacar a importância do CMV para além do transplante, monitorizamos a antigenemia pp65 em uma série de pacientes com LES. Métodos: De março de 2015 a março de 2016, pacientes com LES que apresentaram acometimento renal, febre e infecção indeterminada na internação foram monitorados através da antigenemia pp65. O ensaio de antigenemia, revelada por imunofluorescência, foi correlacionado com achado clínicos e laboratoriais. Resultados: Foram incluídos 19 pacientes com suspeita de infecção indeterminada. Positividade para antigenemia pp65 foi encontrada em sete pacientes (36,8%). A idade média foi de 33,5 ± 11,2 anos; 16 (84%) eram do sexo feminino e 16 (84%) eram negros. Linfopenia, anemia e escore de SLEDAI mais elevado foram significativamente mais comuns em pacientes pp65 positivos. Cinco pacientes receberam terapia antiviral com ganciclovir. Apesar de receber tratamento específico para CMV, um paciente com suspeita de doença por CMV veio a óbito. Conclusões: Antigenemia pp65 pode ser relevante em pacientes com LES, e estudos com maior número de pacientes são necessários para estabelecer a sensibilidade e a especificidade da antigenemia pp65 em diferentes contextos clínicos envolvendo pacientes com LES.

ABSTRACT Introduction: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE). Objective: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients. Methods: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings. Results: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 ± 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease. Conclusions: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients.

RESUMO A infecção por citomegalovírus humano (CMVH) é a principal causa de morbidade em receptores de transplante renal. Este estudo pretende investigar se a expressão de CD64 em polimorfonucleares (PMN) é útil para a detecção de infecção por CMVH em 11 receptores renais durante 60 dias. Do total de pacientes, nove foram positivos para antigenemia pp65 e para CMVH por reação em cadeia da polimerase quantitativa (qPCR), todos apresentando neutrófilos circulantes que expressam CD64 3-4 semanas antes do pico de antigenemia pp65. Esses resultados sugerem que a quantificação de PMN CD64 em conjunto com a antigenemia pp65 pode ser útil para o diagnóstico precoce de HCMV no pós-transplante.

ABSTRACT Human cytomegalovirus (HCMV) infection is the main cause of morbidity in kidney transplant recipients. This study aims to investigate if CD64 expression on polymorphonuclear (PMN) cells is useful for the detection of HCMV infection in eleven kidney recipients during sixty days. From the total patients, nine were positive for both pp65 antigenemia and HCMV by quantitative polymerase chain reaction (qPCR), all of which had circulating neutrophils expressing CD64 3-4 weeks prior to pp65 antigenemia peak. These results suggest that quantification of PMN CD64 together with pp65 antigenemia could be useful for the early diagnosis of HCMV after transplantation.

Abstract Introduction: Human cytomegalovirus is a major cause of morbidity in kidney transplant patients. Objectives: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of Human cytomegalovirus infection. Patients and methods: Independent from the clinical strategy adopted for managing Human cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant. Results: From the 32 transplant recipients, 16 were positive for pp65 antigenemia, with a similar incidence rate in each group. There were no positive results in the first three weeks of monitoring; the positivity rate peaked at week eight. There was a trend for a higher and earlier frequency of positivity in the universal prophylaxis group in which the course of the Human cytomegalovirus infection was also more severe. Despite the differences in clinical picture and in the initial immunosuppressant schedule, the serological response was similar in both groups. Conclusion: Routine monitoring during the first three post-transplant months has a positive impact on the early detection of Human cytomegalovirus viral replication allowing for timely treatment in order to reduce morbidity of the disease. The strategy of universal therapy employing intravenous ganciclovir was associated to a worse clinical course of the Human cytomegalovirus infection suggesting that the use of >10 cells/2 × 105 leukocytes as a cut-off in this setting may be inappropriate.

Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease.

In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-α) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-α levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-α, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-α+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-α treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-α-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-α treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.