Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases

Abstract

BACKGROUND Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVEThe aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913).MAIN CONCLUSIONS YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

Recent sylvatic yellow fever virus transmission in Brazil: the news from an old disease

“…Recently, in severe YF cases, a critical metabolic acidosis leading to the need for hemodialysis [25], increased levels of serum lipase [25,28] and a high prevalence of pancreatitis were observed [25]. These studies highlighted the importance of pancreatitis in the evolution of YF and the need for further studies addressing this issue [25,28].…”

“…After six days of hospitalization, the child died, and postmortem analysis showed wild-type YFV RNA in the cerebrospinal fluid [29]. The persistence of the wild-type YFV genome has been demonstrated in serum [28] and in urine [28,30], until 28 and 47 days after the onset of symptoms, respectively. These findings indicate that YFV might persist in the host for more extended periods than previously thought.…”

“…During the recent epidemics in Brazil, the most common signs and symptoms observed in humans were fever, headache, vomiting, jaundice, chills, nausea, abdominal pain, myalgia, arthralgia, rash, diarrhea, bleeding or hemorrhagic signs [24][25][26][27]. Recently, in severe YF cases, a critical metabolic acidosis leading to the need for hemodialysis [25], increased levels of serum lipase [25,28] and a high prevalence of pancreatitis were observed [25]. These studies highlighted the importance of pancreatitis in the evolution of YF and the need for further studies addressing this issue [25,28].…”

“…Studies have also been conducted to investigate the predictors of severity and death in different groups of YF patients. Age and elevated levels of AST, ALT, and creatinine have been independently associated with mortality in YF patients [26], while higher values of serum lipase and lower values of factor V were related to severe cases [28]. Kallas and colleagues (2019) analyzed data from 76 YF patients and observed that age, neutrophil count, AST, and viral load were independently related with death [27].…”

Yellow fever disease in a renal transplant recipient: Case report and literature review

“…Clinical severity of YF seems to be related to the virus strain virulence and to host factors such as prior immunity . Previous studies in the general populations have shown association between high concentration of transaminases, bilirubin, blood urea nitrogen, serum level of lipase, and factor V as risk factors for death . The behavior of YF and other arbovirus infections in solid organ transplant recipients remains not fully understood …”