Severe yellow fever revisited: contemporary clinical observations challenge classical descriptions

Abstract Background Severe yellow fever (YF) is classically defined by fever, jaundice, and hemorrhagic manifestations. However, whether these features accurately reflect early presentations in contemporary clinical settings remains uncertain. We aimed to characterize the clinical course of severe YF in a modern tertiary-care setting during a recent outbreak in Brazil. Methods We conducted a retrospective descriptive cohort study of patients with confirmed YF admitted to a tertiary referral center in São Paulo, Brazil, between January 2018 and December 2019. All patients had YF confirmed by RT-qPCR and presented within seven days of symptom onset. Clinical and laboratory data were collected from medical records, and patients were followed throughout hospitalization. Results Among 126 patients, 45% died, 50% survived, and 5% underwent liver transplantation. Most deaths occurred within 11 days of symptom onset. Although fever was commonly reported prior to admission, only one-third of patients remained febrile during hospitalization, while hypothermia was observed in 93%. Jaundice, a hallmark feature of YF, was absent at admission in 35% of patients and typically developed later in the disease course. Neurological involvement occurred in nearly half of cases, and laboratory findings suggested frequent rhabdomyolysis and pancreatic injury. Markers of hepatic dysfunction and coagulopathy were more pronounced among patients with fatal outcomes. Conclusions Severe YF frequently presents without classical features such as fever and jaundice in its early phase, challenging current clinical paradigms. Recognition of these atypical early presentations may be critical to improving timely diagnosis and clinical management in endemic settings.