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.

Cerebrospinal fluid in COVID-19: A systematic review of the literature

“…The CSF SARS-CoV-2 PCR resulted positive for 16/303 (5%) patients, all of whom had symptoms that localized to the CNS (16/238 (7%) patients with symptoms that localized to the CNS): 8/16 (50%) who had encephalopathy/coma +/- seizures, 4/16 (25%) who had headache +/- encephalopathy, 1/16 (6%) who had cerebellar symptoms, 1/16 (6%) who had paresthesias, 1/16 (6%) who had seizures without encephalopathy and 1/16 (6%) who had vision loss ( Table 2 ) [ [26] , [27] , [28] , [29] , 150 , 164 , 180 , 195 , 199 , 224 , 225 , 227 , 236 , 238 , 241 ]. The cycle threshold (Ct; the number of amplification cycles required for the target gene to exceed the threshold, which is inversely related to viral load) was only provided for 2/16 (13%) patients with a positive CSF SARS-CoV-2 PCR (37.12, 37.52 and 36.44 for the N1 gene, but negative for N2 for the patient reported by Moriguchi et al and 34.29 for the patient reported by Virhammar et al), though Fadakar et al noted that a Ct of 35 was the cutoff for a positive SARS-CoV-2 PCR [ [26] , [27] , [28] , [29] , 150 , 164 , 180 , 184 , 195 , 199 , 224 , 225 , 227 , 236 , 238 , 241 ]. There were 6/16 (38%) patients who did not have a positive nasopharyngeal/oropharyngeal SARS-CoV-2 PCR, 1 of whom had positive SARS-CoV-2 serum antibodies [ 26 , 27 , 153 , 184 , 241 , 250 ].…”

“…The majority (12/16, 75%) of patients with a positive CSF SARS-CoV-2 PCR were admitted to the hospital because of neurological symptoms [ [26] , [27] , [28] , [29] , 150 , 164 , 180 , 195 , 224 , 236 , 241 ]. There were 10/16 (63%) patients who had acute findings on neuroimaging and 5/16 (31%) patients who had acute findings on chest imaging [ 26 , 27 , 150 , 153 , 164 , 180 , 199 , 225 , 227 , 236 , 238 ]. CSF WBC count, when provided, ranged from 0 to 90 cells/μL for every patient except the patients reported by Mardani et al and Yousefi et al, who had a CSF WBC count of 1,920 cells/μL (90% neutrophils) and 1,870 cells/μL (90% neutrophils, CSF RBC count of 350 cells/μL), respectively [ [26] , [27] , [28] , [29] , 150 , 164 , 180 , 195 , 199 , 224 , 225 , 227 , 238 , 241 ].…”

“…There were 10/16 (63%) patients who had acute findings on neuroimaging and 5/16 (31%) patients who had acute findings on chest imaging [ 26 , 27 , 150 , 153 , 164 , 180 , 199 , 225 , 227 , 236 , 238 ]. CSF WBC count, when provided, ranged from 0 to 90 cells/μL for every patient except the patients reported by Mardani et al and Yousefi et al, who had a CSF WBC count of 1,920 cells/μL (90% neutrophils) and 1,870 cells/μL (90% neutrophils, CSF RBC count of 350 cells/μL), respectively [ [26] , [27] , [28] , [29] , 150 , 164 , 180 , 195 , 199 , 224 , 225 , 227 , 238 , 241 ]. The CSF RBC count was provided for 7/16 (44%) patients, 1 of whom had 0 cells/μL; the remainder had a CSF RBC count of 50–1,685 cells/μL [ 28 , 29 , 180 , 184 , 227 , 241 ].…”

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS‐CoV‐2 infection

“…On June 26, Westhoff et al 19 reported a 69‐year‐old man, who suffered from COVID‐19 pneumonia, meningoencephalitis, and nephritis. RT‐PCR test was positive for SARS‐CoV‐2 in the CSF and the biopsy specimens from the kidneys.…”

Lessons for the clinical nephrologist: recurrence of nephrotic syndrome induced by SARS-CoV-2

“…Moreover, the differential effects of SARS-CoV-2 on tubular and glomerular cells illustrate that even within one organ, the virus can elicit a variety of clinical scenarios. We have previously described the detection of SARS-CoV-2 RNA by in situ hybridization in the interstitium and tubular cells of a renal allograft leading to acute kidney injury [6]. The present case shows that SARS-CoV-2 is able to induce different clinical presentations by infiltration of the same organ.…”