Background Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused ~2.1 million cases and over 600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological and virus genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. Methods Sera, cerebrospinal fluid (CSF) and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue (DENV) and Zika virus (ZIKV). Clinical, epidemiological and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. Results 68 fatal cases had CHIKV infection confirmed by RT-qPCR (52.9%), viral antigen (41.1%), and/or specific-IgM (63.2%). Co-detection of CHIKV with DENV were found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV-deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the sub-acute phase. Genetic analysis showed circulation of two CHIKV-East Central South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. Conclusion The investigation of the largest cross-sectional cohort of CHIKV-deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and non-risk groups, including young adults.

RESUMOO lúpus eritematoso sistêmico (LES) é uma doença autoimune crônica, cujo desenvolvimento pode estar associado à infecção por vírus, como o vírus Epstein-Barr (EBV), parvovírus B19 e vírus linfotrópico de células T humanas (HTLV). Durante o período de junho a setembro de 2014, foi realizado um estudo transversal, incluindo 85 pacientes oriundos do Hospital Jean Bitar, na Cidade de Belém, Estado do Pará, Brasil. Foi realizada a pesquisa de anticorpos específicos contra os agentes virais estudados, assim como pesquisa da presença do genoma para EBV e HTLV. Foram avaliadas também variáveis clínicas e epidemiológicas. A maioria dos pacientes eram mulheres, tinham média de idade de 30 anos e se declararam brancos. Para EBV, detectou-se positividade de 37,6% para IgM, 98,8% para IgG e 2,4% por qPCR, com quantificações de 85.028 e 298 cópias do genoma/mL de plasma. Para B19, a positividade para IgM foi 0% e para IgG 67,1%. Não houve detecção sorológica ou por qPCR de HTLV. Foi verificada relação estatisticamente significante entre a positividade para IgM anti-EBV e pacientes mais jovens. Esse achado pode estar relacionado com a maior eficiência na produção dessa imunoglobulina nas infecções primárias agudas, que ocorrem geralmente em indivíduos infantes ou adultos jovens. Adicionalmente, o resultado de IgG anti-B19 foi associado à idade avançada dos pacientes, provavelmente por um maior tempo de exposição ao vírus aliado à persistência desse marcador após o contato. A presença dos marcadores não esteve associada às variáveis clínicas e epidemiológicas. Entretanto, o percentual de positividade para o marcador de infecção aguda por EBV pode sugerir um envolvimento do vírus com o LES. Palavras-chave: Lúpus Eritematoso Sistêmico; Vírus Epstein-Barr; Parvovírus B19; HTLV. ARTIGO ORIGINAL | ORIGINAL ARTICLE ABSTRACT Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose development may be associated with viral infections, such as Epstein-Barr virus (EBV), parvovirus B19, and human T-cell lymphotropic virus (HTLV).A cross-sectional study was performed between June and September 2014 involving 85 patients from the Hospital Jean Bitar, located in Belém, Pará State, Brazil. A survey of specific antibodies against the studied viral agents was conducted, in addition to a survey of the EBV and HTLV genomes. Clinical and epidemiologic variables were also evaluated. Most patients were female, approximately 30 years old, and declared themselves as Caucasians. The following positive results were detected for EBV: IgM = 37.6%, IgG = 98.8%, and qPCR = 2.4%, with 85,028 and 298 copies of the genome per milliliter of plasma. Positive results for B19 were: IgM = 0%, IgG = 67.1%. Serological or qPCR detection did not reveal HTLV. A significant statistical correlation was observed between anti-EBV IgM antibodies and younger patients. These findings may be related to the highly efficient production of this immunoglobulin during acute primary infections, which frequently occurs in children and young adults. Furthermore, t...