Coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre‐vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID‐19 in kidney and liver transplant recipients in Denmark in the post‐vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first‐positive SARS‐CoV‐2 PCR test. The cumulative incidence of first‐positive SARS‐CoV‐2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8–12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4–13.8] vs. 7.4% [95% CI: 5.1–9.8], p = .009). After the first‐positive SARS‐CoV‐2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9–39.1), and 30‐day all‐cause mortality was 3.7% (95% CI: 0.5–6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1–34.6] vs. 48.5% [95% CI: 31.4–65.5], p = .011), as was mortality (1.8% [95% CI: 0.0–4.3] vs. 9.1% [95% CI: 0.0–18.9], p = .047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS‐CoV‐2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.

IntroductionInfectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.MethodsThis was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.ResultsIn total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.ConclusionWe found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.

IntroductionHerpes virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of positive herpes virus (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1/2 (HSV-1/2), and varicella zoster virus (VZV)) PCR tests during the first year post-transplantation and assess whether a model including immune function pre-transplantation and three months post-transplantation could predict a subsequent positive herpes virus PCR.MethodsAll participants were preemptively screened for CMV, and EBV IgG-negative participants were screened for EBV during the first year post-transplantation. Herpes virus PCR tests for all included herpes viruses (CMV, EBV, HSV-1/2, and VZV) were retrieved from the Danish Microbiology database containing nationwide PCR results from both hospitals and outpatient clinics. Immune function was assessed by whole blood stimulation with A) LPS, B) R848, C) Poly I:C, and D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α, and IFN-γ) were measured using Luminex.ResultsWe included 123 liver (54%), kidney (26%), and lung (20%) transplant recipients. The cumulative incidence of positive herpes virus PCR tests was 36.6% (95% CI: 28.1-45.1) during the first year post-transplantation. The final prediction model included recipient age, type of transplantation, CMV serostatus, and change in Poly I:C-induced IL-12p40 from pre-transplantation to three months post-transplantation. The prediction model had an AUC of 77% (95% CI: 61-92). Risk scores were extracted from the prediction model, and the participants were divided into three risk groups. Participants with a risk score <5 (28% of the cohort), 5-10 (45% of the cohort), and >10 (27% of the cohort) had a cumulative incidence of having a positive herpes virus PCR test at 5.8%, 25%, and 73%, respectively (p < 0.001)ConclusionIn conclusion, the incidence of positive herpes virus PCR tests was high, and a risk model including immune function allowed the prediction of positive herpes virus PCR and may be used to identify recipients at higher risk.