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BackgroundKidney transplant recipients (KTRs) with COVID-19 have poor outcomes compared to non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.{square} MethodsClinical data were collected by chart review. PAXgene blood RNA was poly-A selected and RNA sequencing was performed to evaluate transcriptome changes. ResultsA total of 64 cases of COVID-19 in KTRs were enrolled, including 31 acute cases (< 4 weeks from diagnosis) and 33 post-acute cases (>4 weeks). In the blood transcriptome of acute cases, we identified differentially expressed genes (DEGs) in positive or negative association COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways, but downregulation of T-cell and adaptive immune-activation pathways proportional to severity score. This finding was independent of lymphocyte count and despite reduction in immunosuppression (IS) in most KTRs. Comparison with post-acute cases showed "normalization" of these enriched pathways after >4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of IS. The latter analysis was adjusted for COVID-19 severity score and lymphocyte count. DEGs associated with worsening disease severity in a non-KTR cohort with COVID-19 (GSE152418) showed significant overlap with KTRs in these identified enriched pathways. ConclusionBlood transcriptome of KTRs affected by COVID-19 shows decrease in T-cell and adaptive immune activation pathways during acute disease that associate with severity despite IS reduction and show recovery after acute illness. Significance statementKidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of maintenance immunosuppression is pursued. Surprisingly, reported rates of acute rejection have been low despite reduced immunosuppression. We evaluated the peripheral blood transcriptome of 64 KTRs either during or after acute COVID-19. We identified transcriptomic signatures consistent with suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease, even after adjustment for lymphocyte number. Our transcriptomic findings of immune-insufficiency during acute COVID-19 provide an explanation for the low rates of acute rejection in KTRs despite reduced immunosuppression. Our data support the approach of temporarily reducing T -cell-directed immunosuppression in KTRs with acute COVID-19.
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BACKGROUND: Involvement of the central nervous system (CNS) by a tuberculosis abscess is a rare form of extra-pulmonary tuberculosis. With proper treatment, the abscess most commonly follows a pattern of continued reduction in size. CASE DESCRIPTION: A 71-year-old male with a past medical history of kidney transplant on immunosuppressive therapy, presented to the hospital with a 1-day history of headache. On physical examination, the patient had no focal neurological symptoms. Initial laboratory reports were unremarkable. Contrast enhanced magnetic resonance imaging (MRI) was performed, which showed a ring enhancing mass and perilesional edema in the left cerebellar hemisphere. The patient underwent a left posterior fossa biopsy and drainage. The lesion was encapsulated with a purulent center. Cultures revealed pan-sensitive mycobacterium tuberculosis and the patient was started on rifampicin, isoniazid, pyrazinamide, ethambutol, and B6. The patient was monitored carefully and brain MRIs were obtained at 1, 4, 9, 11, and 14 months. It was noted that the tuberculosis abscess had grown in size from month 4 to month 9 of treatment. Since the patient's neurologic examination and symptoms were stable at that time, the drug regimen was not changed. The 14-month follow up MRI showed that the abscess had nearly resolved. CONCLUSION: Rarely, the pattern of CNS tuberculosis abscess evolution may include growth, even with proper treatment. This pattern does not necessarily signify treatment failure, as our abscess resolved without change in treatment. Given the possibility of asymptomatic abscess enlargement, close clinical and imaging follow up are crucial in management of these cases.
