Allograft infiltration and meningoencephalitis by SARS-CoV-2 in a pancreas-kidney transplant recipient

Abstract

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) preferentially affects epithelia of the upper and lower respiratory tract. Thus, impairment of kidney function has been primarily attributed until now to secondary effects such as cytokine release or fluid balance disturbances. We provide evidence that SARS-CoV-2 can directly infiltrate a kidney allograft. A 69-year-old male, who underwent pancreas-kidney transplantation 13 years previously, presented to our hospital with coronavirus disease 2019 (COVID-19) pneumonia and impaired pancreas and kidney allograft function. Kidney biopsy was performed showing tubular damage and an interstitial mononuclear cell infiltrate. Reverse transcriptase polymerase chain reaction from the biopsy specimen was positive for SARS-CoV-2. In-situ hybridization revealed SARS-CoV-2 RNA in tubular cells and the interstitium. Subsequently, he had 2 convulsive seizures. Magnetic resonance tomography suggested meningoencephalitis, which was confirmed by SARS-CoV-2 RNA transcripts in the cerebrospinal fluid. The patient had COVID-19 pneumonia, meningoencephalitis, and nephritis. SARS-CoV-2 binds to its target cells through angiotensin-converting enzyme 2, which is expressed in a broad variety of tissues including the lung, brain, and kidney. SARS-CoV-2 thereby shares features with other human coronaviruses including SARS-CoV that were identified as pathogens beyond the respiratory tract as well. The present case should provide awareness that extrapulmonary symptoms in COVID-19 may be attributable to viral infiltration of diverse organs.

FIGURE 1

Thoracic computed tomography showing bilateral ground-glass opacity (arrow) and lung consolidation in subacute coronavirus disease 2019 pneumonia

FIGURE 2

Kidney allograft biopsy showing (A) an interstitial mononuclear cell infiltrate (arrow) and tubular damage in PAS staining. (B) In-situ hybridization using RNA scope visualized SARS-CoV-2 viral RNA as dotted red staining in tubules and interstitial tissue. PAS, periodic acid–Schiff; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

FIGURE 3

Magnetic resonance tomography of the brain. A, Transversal T1-weighted images showing linear meningeal enhancement (arrow). B, Diffusion-weighted images showing a subtle area of diffusion restriction (arrow), and C, T2-weighted images showing edema without mass effect (hyperintensity in the white matter)

FIGURE 4

Timeline of the clinical course. ICU, intensive care unit; MMF, mycophenolate mofetil; MRI, magnetic resonance imaging; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2