Søren Jensen-Fangel

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population.

Persistent symptoms after hospitalization with COVID-19 are common, but the frequency and severity of these symptoms are insufficiently understood. We aimed to describe symptoms and pulmonary function after hospitalization with COVID-19. Patients hospitalized with COVID-19 in Central Denmark Region were invited for follow-up 3 months after discharge. Clinical characteristics, patient reported outcomes (Fatigue Assessment Scale (FAS), anxiety and depression (HADS)), symptoms, pulmonary function test and 6-min walk test were collected. We included 218 patients (mean age 59.9 (95% CI: 58.2, 61.7), 59% males). Fatigue, dyspnea and impaired concentration were the most prevalent symptoms at follow-up. Using FAS, 47% reported mild-to-moderate fatigue and 18% severe fatigue. Mean HADS was 7.9 (95% CI: 6.9, 8.9). FAS was correlated to HADS (β = 0.52 (95% CI: 0.44, 0.59, p < 0.001)). Mean DLCO was 80.4% (95% CI: 77.8, 83.0) and 45% had DLCO ˂ 80%. Mean DLCO was significantly reduced in patients treated in the ICU (70.46% (95% CI 65.13, 75.79)). The highest FAS and HADS were seen in patients with the shortest period of hospitalization (2.1 days (95% CI: 1.4, 2.7)) with no need for oxygen. In conclusion, fatigue is a common symptom after hospitalization for COVID-19 and ICU treatment is associated to decreased diffusion capacity.

Follow-up studies of COVID-19 survivors have been performed to characterize persistence of long-term symptoms, but data are scarce on one year of follow-up. This study provides data from 48 weeks of follow-up after discharge. All patients discharged from the Department of Infectious Diseases at Aarhus University Hospital, Denmark between 1 March and 1 July 2020 were followed for 48 weeks. In total, 45 of 66 eligible patients were interviewed after 48 weeks. The median age was 57 (IQR 51–70) years, the majority were female (53%) and Caucasian (87%). Median BMI was 28.1 (IQR 24.8–32.6) kg/m². One or more comorbidities were registered among 62% of the patients. In total, 39 out of 45 (87%) interviewed patients reported persistence of at least one symptom 48 weeks after hospitalization with COVID-19. Most frequently reported symptoms were fatigue, dyspnea, and concentration difficulties. This study provides new long-term data following COVID-19, contributing to the accumulating data of COVID-19 sequelae. Many patients suffer long-term sequelae and further research is urgently needed to gain further knowledge of the duration and therapeutic options.

To determine complications during outpatient parenteral antimicrobial therapy (OPAT) administrated through a peripheral venous line, PICC-line or PORT-A-CATH (PAC). Catheter related complications in patients with cystic fibrosis during OPAT were identified through a retrospective review of patient files supplemented by an interview. In 64 treatment episodes with a peripheral venous line, 51 (79.7 %) used bolus injection and 13 (20.3 %) used infusion pump. 27 out of 51 (53.0 %) bolus injection episodes experienced complications, which required removal. None were observed for infusion pump treatments. The infectious complications requiring removal of peripheral venous line were 9 out of 23 (39.1 %) for the PICC line and 11 out of 26 (42.3 %) for the PAC. No anaphylaxis was observed during the OPAT treatments. Our data indicate that using an infusion pump to administer the antibiotic treatment minimized peripheral venous line complications. The frequency of complications leading to removal of the catheter is about the same for PICC-lines and PACs, but the average life-time of the latter is much longer. Allergic reactions are not a major problem.

Staphylococcus aureus is a leading cause of bloodstream infections among hemodialysis patients and of exit-site infections among peritoneal dialysis patients. However, the risk and prognosis of Staphylococcus aureus bacteremia among end-stage renal disease patients have not been delineated. In this Danish nationwide, population-based cohort study patients with end-stage renal disease and matched population controls were observed from end-stage renal disease diagnosis/sampling until first episode of Staphylococcus aureus bacteremia, death, or end of study period. Staphylococcus aureus positive blood cultures, hospitalization, comorbidity, and case fatality were obtained from nationwide microbiological, clinical, and administrative databases. Incidence rates and risk factors were assessed by regression analysis. The incidence rate of Staphylococcus aureus bacteremia was very high for end-stage renal disease patients (35.7 per 1,000 person-years; 95% CI, 33.8-37.6) compared to population controls (0.5 per 1,000 person-years; 95% CI, 0.5-0.6), yielding a relative risk of 65.1 (95% CI, 59.6-71.2) which fell to 28.6 (95% CI, 23.3-35.3) after adjustment for sex, age, and comorbidity. After stratification for type of renal replacement therapy, we found the highest incidence rate of Staphylococcus aureus bacteremia among hemodialysis patients (46.3 per 1,000 person-years) compared to peritoneal dialysis patients (22.0 per 1,000 person-years) and renal transplant recipients (8.9 per 1,000 person-years). In persons with Staphylococcus aureus bacteremia, ninety-day case fatality was 18.2% (95% CI, 16.2%-20.3%) for end-stage renal disease patients and 33.7% (95% CI, 30.3-37.3) for population controls. Patients with end-stage renal disease, and hemodialysis patients in particular, have greatly increased risk of Staphylococcus aureus bacteremia compared to population controls. Future challenges will be to develop strategies to reduce Staphylococcus aureus bacteremia-related morbidity and death in this high-risk population.

Individuals with end-stage renal disease (ESRD) have excess risk of various cancer types. However, the total burden of human papillomavirus-related cancers remains unknown. We performed a nationwide observational cohort study during 1994–2010. For each person with ESRD, we sampled 19 population controls (without ESRD) matched on age, gender and municipality. Participants were followed until first diagnosis of human papillomavirus-related cancer, death, emigration, or 31 December 2010, whichever came first. Human papillomavirus-related cancers were extracted from Danish medical administrative databases. We considered cancers of the cervix, vulva, vagina, penis, anus, and subsets of head and neck cancers as human papillomavirus-related. We calculated incidence rates of human papillomavirus-related cancer and used Poisson regression to identify risk factors for human papillomavirus-related cancer. Among 12,293 persons with ESRD and 229,524 population controls we identified 62 and 798 human papillomavirus-related cancers, respectively. Incidence rates of human papillomavirus-related- cancer were 102 per 100,000 person-years (95% confidence interval [CI]; 79.5-131) among persons with ESRD and 40.8 per 100,000 person-years (95% CI; 38.1-43.7) among population controls. ESRD patients had 4.54 (95% CI, 2.48-8.31) fold increased risk of anal cancer and 5.81 fold (95% CI; 3.36-10.1) increased risk of vulvovaginal cancer. Adjusted for age, comorbidity, and sex, ESRD patients had 2.41 (95% CI; 1.83-3.16) fold increased risk of any human papillomavirus-related cancer compared with population controls. Compared with dialysis patients renal transplant recipients had an age-adjusted non-significant 1.53 (95% CI, 0.91-2.58) fold higher risk of human papillomavirus-related cancer. Persons with ESRD have excess risk of potentially vaccine-preventable human papillomavirus-related cancers.

Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial.