Risk factors associated with in hospital mortality during yellow fever outbreak in Brazil

Max McClure ¹ Izabela Rezende ^2* Leonardo Soares Pereira ³ Maria Rita Teixeira Dutra ³ Jordana Rodrigues Barbosa Fradico ⁴ Rodrigo Macedo ³ Marcelle Cardoso Marçal ³ Lívia Soares Coelho Fonte Boa ³ Alexandre Maurício Castro Bragato ³ Flávio Augusto de Almeida Faria ³ Livia Pamplona ³ Rodrigo Fabiano do Carmo Said ⁵ Carlos Eduardo Calzavara-Silva ⁶ DARIO RAMALHO ³ Cintia Lopes de Brito Magalhães ⁷ Pedro Augusto Alves ⁶ Thaysa Drummond Palmeira Gama ³ Gláucia Fernandes Cota ⁸ Thomas P Monath ⁹ Olindo Assis Martins Filho ⁴ Marcelo Antônio Pascoal-Xavier ⁶ Andréa Teixeira-Carvalho ⁴ Betania Paiva Drumond ¹⁰ Angelle Desiree LaBeaud ¹¹

• ¹ University of California, San Francisco, San Francisco, California, United States
• ² Stanford University, Stanford, United States
• ³ Eduardo de Menezes Hospital, Belo Horizonte, Mato Grosso, Brazil
• ⁴ Integrated Research Group on Biomarkers, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte, Mato Grosso, Brazil
• ⁵ Pan American Health Organization/World Health Organization, Brasilia, Brazil
• ⁶ Laboratory of Viral Disease Immunology, René Rachou Institute, Oswaldo Cruz Foundation, Belo Horizonte, Mato Grosso, Brazil
• ⁷ Nucleus of Research in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil
• ⁸ René Rachou Institute, Oswaldo Cruz Foundation (Fiocruz), Belo Horizonte, Minas Gerais, Brazil
• ⁹ Crozet BioPharma LLC, Denver, Massachusetts, United States
• ¹⁰ Laboratory of Viruses, Microbiology Department, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
• ¹¹ School of Medicine, Stanford University, Stanford, California, United States

Objective: To characterize the clinical manifestations of yellow fever disease and identify risk factors for mortality, a retrospective study was conducted in the referral center for infectious diseases (Hospital Eduardo de Menezes - HEM) in Belo Horizonte, Brazil, including data from 283 patients with confirmed YF infection. Methods: To characterize the clinical manifestations of yellow fever and identify risk factors for mortality, a retrospective study was conducted in the referral center for infectious diseases (Hospital Eduardo de Menezes - HEM) in Belo Horizonte, Minas Gerais, Brazil. Analysis included data from 283 patients with confirmed YF infection, older than 13 years old who presented to HEM between January 2017 and June 2018. In-hospital mortality (hypothesis formulated after data collection), demographic factors and clinical and laboratory assessments were used. Results: Study patients were mainly men (87.6%), with a median age of 46.0 (IQR 36.5, 57.0). 131 (46.3%) patients were admitted to the ICU, and 62 (22.0%) used invasive mechanical ventilation for a median of 2 days (IQR 1, 3). The median (IQR) total length of stay (LOS) in the ICU was 6 days (IQR 4, 8). The in-hospital mortality rate was 24.0%. Age was significantly higher in fatal (median 49.5, IQR 41.0, 61.0]) than in nonfatal cases (46 [36, 55]) (p<0.01). Male sex was associated with an increased risk of death (RR 4.66, 95% CI 1.19, 18.2; p<0.01). Most common symptoms and signs on admission to HEM were fever (31.9%), myalgia (27.8%), jaundice (24.3%), headache (23.9%), abdominal pain (16.1%), vomiting (12.2%), weakness (10.4%), and arthralgias (10.0%). Initial viral load above the cutoff of 4.45 log10 copies/mL was significantly associated with death prior to discharge (OR 12.2; CI 2.83, 92.3). Five factors were significantly related to increased odds of death prior to discharge: log-transformed AST (OR 3.65; CI 2.02, 7.81; p<0.001), log-transformed INR (OR 7.40; CI 1.31, 33.0; p=0.010), log-transformed lactate (OR 4.57; CI 1.48, 17.1; p=0.013), log-transformed WBC (OR 4.33; CI 1.19, 18.5; p=0.034), and age (OR 1.06; CI 1.01, 1.12; p=0.026). Conclusions and Relevance: AST, INR, lactate, WBC, and age are statistically associated with death prior to discharge in YF patients.