Powassan Virus Crosses Beyond the Brain in a Fatal Transplant Case
A fatal case of Powassan virus infection in a 38-year-old liver transplant recipient in Pennsylvania documented something rarely seen in human disease: disseminated infection beyond the central nervous system, with viral material identified in brain, lung, kidney, and circulating cells. The patient developed malaise, headache, fever, leukocytosis, and then multiple generalized seizures only six weeks after orthotopic liver transplantation. Rapid neurologic decline followed, and the case ended in death despite extensive diagnostic workup and urgent evaluation for alternative infectious causes.
Powassan virus lineage 2, also called deer tick virus, remains an uncommon but highly lethal tickborne flavivirus. In this patient, the clinical picture initially pointed toward fulminant encephalitis of uncertain cause, and rabies entered the differential because of the speed of deterioration and the severity of the imaging findings. The final diagnosis depended on postmortem and late antemortem testing, which identified Powassan virus RNA and antigen in multiple tissues and confirmed a more invasive pattern than the usual neurotropic presentation.
Imaging and Cerebrospinal Fluid Signaled Fulminant Encephalitis
Magnetic resonance imaging showed hydrocephalus and rapidly progressive enhancement involving the cerebellum, brainstem, white matter, cortex, leptomeninges, and spinal cord. Cerebrospinal fluid studies were consistent with viral encephalitis. A brain biopsy showed lymphocytic encephalitis without a specific infectious signature, while operative findings included necrotic tissue and hemorrhage. Neurologic function worsened after the procedure, and the patient was transitioned to comfort care before death.
The timing of viral detection mattered. CSF reverse transcription PCR was positive for Powassan virus lineage 2 the day before death, while serum IgM became positive only after death. Earlier metagenomic sequencing of a CSF sample was negative, a result that fits with low viral burden or assay sensitivity limits rather than absence of infection. In this setting, negative early molecular testing did not exclude the diagnosis, especially when the inflammatory picture and imaging were already advancing quickly.
The case also illustrates a familiar problem in severe encephalitis: the leading diagnosis can be wrong when the syndrome is unusually aggressive. Rabies testing was pursued because common causes had been ruled out, and prior rabies vaccination complicated interpretation of serologic findings. Antemortem serum and CSF testing detected IgG but not IgM, with high serum titers and low CSF titers. Postmortem rabies studies, including immunohistochemistry and PCR from brain and liver, were negative.
Autopsy Showed Widespread Viral Injury Outside the CNS
Autopsy findings extended the story beyond encephalitis. The brain showed a 3.2-cm focus of right basal ganglia necrosis and hemorrhage, diffuse edema, and bilateral basal ganglia softening. Histopathology revealed widespread meningoencephalitis involving the cerebrum, pons, and cerebellum, with diffuse lymphoplasmacytic parenchymal and leptomeningeal inflammation, microgliosis, and marked Purkinje cell loss. Microglial nodules were not prominent, and no Negri bodies were seen. Standard viral stains were negative, but Powassan antigen and nucleic acids were detected in postmortem brain samples by immunohistochemistry, in situ hybridization, and reverse transcription PCR.
The lung and kidney findings were especially important because they extend the known clinicopathologic range of Powassan virus. Lung tissue showed mild lymphocytic pneumonitis and bronchiolar epithelial apoptosis, with Powassan antigen and RNA in bronchiolar epithelial cells. Kidney tissue showed acute tubular necrosis and mononuclear peritubular infiltrates. Powassan nucleic acids were also found in rare circulating mononuclear cells in postmortem samples. Mild portal inflammation, sinusoidal congestion, and mild ischemic changes were seen in the donor liver, and Powassan nucleic acids were identified in rare circulating mononuclear cells in postmortem liver allograft samples.
A single sentence captures the clinical consequence: this was not isolated encephalitis.
Immunosuppression Likely Shaped the Disease Course
The patient had undergone orthotopic liver transplantation six weeks earlier and was therefore immunosuppressed at the time of infection. Severe arboviral disease is well recognized in transplant recipients and other immunocompromised patients, where viral control is weaker and multiorgan involvement can emerge alongside neurologic disease. In this case, the combination of recent transplantation and rapidly progressive encephalitis likely increased susceptibility to severe dissemination and limited the host response needed to contain the virus.
The investigation by local and federal public health teams pointed most strongly toward tick exposure as the route of infection. The patient had several plausible opportunities, including a public garden visit, repeated campground visits before and after transplant, and dog walks in natural areas. No definite tick bite was documented, which is a familiar problem in tickborne disease; the absence of a remembered bite does not exclude exposure. Pennsylvania has recorded multiple neuroinvasive Powassan cases over the past decade, and evidence of transmission has been documented across the state.
Why This Case Expands the Clinical Picture of Powassan Virus
Powassan virus has been treated mainly as a neuroinvasive pathogen, and for good reason: most confirmed cases involve the nervous system, and fatalities are overwhelmingly neurologic. Yet the tissue findings in this transplant recipient argue for a broader biologic range. Evidence of infection in bronchiolar epithelium, kidney, and circulating mononuclear cells suggests that Powassan virus can infect non-CNS cell types in vivo, at least in severely immunosuppressed hosts.
That pattern fits with what is already known about related flaviviruses. Yellow fever and West Nile virus can infect renal tubular cells and contribute to kidney injury, and flaviviral nonstructural proteins have been linked to tissue-specific endothelial dysfunction. The new pathology in this case does not prove identical mechanisms, but it does make a direct viral contribution to pulmonary and renal injury plausible rather than speculative.
The practical lesson for clinicians caring for transplant recipients is to keep arboviral infection in the differential when encephalitis is severe, rapidly progressive, and accompanied by organ dysfunction. Powassan virus is still rare, but rarity does not protect against catastrophic outcomes when diagnosis is delayed or when the host cannot contain dissemination. In this patient, the final pathology showed a virus capable of reaching far beyond the brain, and that finding should broaden how severe tickborne encephalitis is approached in immunocompromised adults.