Herpes Simplex Virus Associated Sepsis in an Immunocompetent Adult: The Value of Next-Generation Sequencing
Sepsis is a life-threatening condition characterized by organ dysfunction resulting from a dysregulated host response to infection. Early and accurate identification of the causative pathogen is crucial for effective treatment. However, in cases of atypical infections with rare etiologies, such as herpes simplex virus (HSV) sepsis, rapid diagnosis can be challenging. This case report highlights the value of next-generation sequencing (NGS) in identifying HSV-1 as the causative agent of sepsis in an immunocompetent adult, underscoring the importance of advanced diagnostic techniques in managing critically ill patients.
A 33-year-old previously healthy Chinese man presented to a local hospital with a 5-day history of fever, upper abdominal pain, vomiting, and diarrhea. Initial laboratory findings indicated liver and kidney function impairments. The patient was treated for suspected bacterial infection and anuria. However, his condition deteriorated, and by day 8 of illness, he became confused and disoriented. He was subsequently transferred to the emergency room of a tertiary care hospital.
Upon arrival, the patient exhibited severe elevations of transaminases and moderate coagulopathy. Viral serologies for hepatitis A, B, C, and E were negative, and a chest X-ray was normal. Computed tomography of the brain and abdomen revealed hepatomegaly and a small amount of ascites. By day 10 of illness, the patient developed status epilepticus and required intubation for airway protection. He was admitted to the intensive care unit (ICU) for further management.
On admission, the patient’s Glasgow Coma Scale was E1V1M1, and his pulse rate was 105 beats per minute. Physical examination was unremarkable, and there were no orolabial lesions. Serological tests for HSV-IgM, Coxsackievirus A16-IgM, Toxoplasma-IgM, Rubella virus-IgM, Cytomegalovirus-IgM, Parvovirus B19-IgM, and Cytomegalovirus-DNA were all negative. Blood and urine cultures were also negative. Epstein-Barr virus (EBV)-DNA in peripheral blood was detected at 5400 copies/mL. Anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, and antibodies for primary biliary cholangitis and autoimmune hepatitis were negative.
Twenty-eight hours after admission, the patient’s clinical condition worsened, with severe hypotension. Pulmonary artery catheterization revealed a cardiac output of 10.2 L/min and systemic vascular resistance of 384 dynes·s·cm⁻⁵, with a blood pressure of 74/53 mmHg. Despite aggressive supportive measures, the patient died from refractory hypotension on day 12 of illness. The family declined an autopsy.
The following day, NGS of the patient’s blood revealed 14,054 reads of HSV-1 DNA, with a coverage rate of 87.03% of the HSV-1 genome. This finding was confirmed by a positive HSV-1 polymerase chain reaction (PCR) of stored sera obtained antemortem. Interestingly, both IgG and IgM for HSV-1 and HIV-2 were negative.
This case illustrates the diagnostic challenges associated with HSV sepsis, particularly in immunocompetent individuals. The non-specific clinical presentation, lack of awareness, and delay in diagnosis and treatment contribute to the high mortality rate associated with this condition. NGS proved to be a valuable tool in this case, providing rapid and specific identification of HSV-1 as the causative pathogen.
Fulminant HSV hepatitis with liver failure should be considered in patients presenting with elevated international normalized ratio (INR) and status epilepticus. The diagnostic gold standard for HSV hepatitis is liver biopsy; however, this was not performed in this case due to the high risk of bleeding. Earlier initiation of systemic acyclovir could have been pivotal in managing this patient, highlighting the advantage of NGS for rapid universal pathogen detection in critically ill patients.
The presence of EBV DNA and the absence of HSV IgM might suggest EBV-associated hemophagocytic syndrome. However, the EBV DNA copy number in this patient was similar to that observed in patients without EBV disease. A positive PCR for HSV without serological evidence of HSV is highly indicative of an acute infection.
In conclusion, this case underscores the potential of NGS as a single, universal pathogen detection method for sepsis with rare etiologies. The rapid and accurate identification of the causative pathogen can significantly impact patient care, particularly in critically ill individuals. This case also highlights the importance of considering HSV infection in the differential diagnosis of sepsis, even in immunocompetent adults.
doi.org/10.1097/CM9.0000000000000893
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