COVID-19 in Kidney Transplant Recipient and Waitlist Patients: Implications of Chest Radiographic Severity Score.

PURPOSE: To evaluate the chest radiographic severity score (CXR-SS) for coronavirus disease 2019 (COVID-19) patients who are kidney transplant recipients compared with patients on the waitlist. STUDY DESIGN AND METHODS: This retrospective cohort includes 78 kidney transplant recipients (50 men, mean age 59.9±11.9 y) and 59 kidney transplant waitlist patients (33 men, mean age 58.8±10.8 y) diagnosed with COVID-19 between March 15 and May 30, 2020 with reverse transcriptase-polymerase chain reaction. Patient chest radiographs were divided into 6 zones and examined for consolidation. Primary outcome was mortality. Secondary outcomes included hospital admission, intensive care unit (ICU) admission, and intubation. Predictors of our primary and secondary outcomes were identified by bivariate analysis and multivariate regression analysis. RESULTS: No significant difference was found in CXR-SS between 2 groups (P=0.087). Transplant recipients had significantly higher rates of hospitalization (odds ratio, 6.8; 95% confidence interval: 1.7, 39.3; P<0.001), ICU admission (odds ratio, 6.5; 95% confidence interval [CI]: 1.8-35.9; P=0.002), intubation (odds ratio, 11; 95% CI: 2.4-96.9; P=0.001), and mortality (odds ratio, 17; 95% CI: 3.9-153.1; P<0.001). A higher CXR-SS was not predictive of mortality, intubation, or ICU admission. CXR-SS was associated with hospital admission overall (odds ratio, 1.613; 95% CI: 1.04-2.49; P=0.0314). CONCLUSION: The CXR-SS was not predictive of mortality, ICU admission or intubation in our population. Kidney transplant patients with COVID-19 had near universal hospital admission, more than one-third mortality and about a quarter were intubated and admitted to the ICU-all significantly worse outcomes than for patients on the transplant waitlist.

A TRAF3-NIK module differentially regulates DNA vs RNA pathways in innate immune signaling.

Detection of viral genomes by the innate immune system elicits an antiviral gene program mediated by type I interferons (IFNs). While viral RNA and DNA species induce IFN via separate pathways, the mechanisms by which these pathways are differentially modulated are unknown. Here we show that the positive regulator of IFN in the RNA pathway, TRAF3, has an inhibitory function in the DNA pathway. Loss of TRAF3 coincides with increased expression of the alternative NF-κB-inducing molecule, NIK, which interacts with the DNA pathway adaptor, STING, to enhance IFN induction. Cells lacking NIK display defective IFN activation in the DNA pathway due to impaired STING signaling, and NIK-deficient mice are more susceptible to DNA virus infection. Mechanistically, NIK operates independently from alternative NF-κB signaling components and instead requires autophosphorylation and oligomerization to activate STING. Thus a previously undescribed pathway for NIK exists in activating IFN in the DNA pathway.