Given the importance of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the prevention of severe coronavirus disease 2019 (COVID-19), detailed long-term analyses of neutralising antibody responses are required to inform immunisation strategies. In this study, longitudinal neutralising antibody titres to an ancestral SARS-CoV-2 isolate and cross-neutralisation to delta and omicron isolates were analysed in individuals previously infected with SARS-CoV-2, vaccinated against COVID-19, or a complex mix thereof with up to two years of follow-up. Both infection-induced and vaccine-induced neutralising responses against SARS-CoV-2 appeared to follow similar decay patterns. Following vaccination in previously infected individuals, neutralising antibody responses were more durable than prior to vaccination. Further, this study shows that vaccination after infection, as well as booster vaccination, increases the cross-neutralising potential to both delta and omicron SARS-CoV-2 variants. Taken together, these results suggest that neither type of antigen exposure is superior for neutralising antibody durability. However, these results support vaccination to increase the durability and cross-neutralisation potential of neutralising responses, thereby enhancing protection against severe COVID-19. This work was supported by grants from The Capital Region of Denmark's Research Foundation, the Novo Nordisk Foundation, the Independent Research Fund Denmark, the Candys Foundation, and the Danish Agency for Science and Higher Education.

With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty^®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria^®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty^® or Spikevax^®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID₅₀: 2525, IQR: 1667–4313) and vector–mRNA (ID₅₀: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID₅₀: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria^® (p = 0.0072). Between mRNA–mRNA and vector–mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure.

This study aimed to investigate psychological distress among patients hospitalized with a COVID-19 diagnosis in Denmark during the first 12 months of the pandemic and to assess changes in psychological distress in the three months following discharge. A single-center prospective observational survey study among patients hospitalized with a COVID-19 diagnosis between May 2020 and May 2021 was conducted. Participants completed a survey at three time points: at admission, and 1 and 3 months after discharge. Psychological distress was assessed by validated scales measuring symptoms related to depression, anxiety, stress, insomnia, post-traumatic stress disorder (PTSD), and health-related quality of life (HRQoL). In total, 95 patients were included. At admission, the proportion of patients with symptoms of depression was 43%, symptoms of anxiety 32%, moderate/high level of stress 39%, insomnia 52%, and probable/positive PTSD 19%. The burden of symptoms related to depression and anxiety decreased significantly over time, while there was no significant change over time in stress, insomnia, or PTSD. Suboptimal levels of physical and mental HRQoL were detected at admission but improved over time. Patients hospitalized due to COVID-19 during the first year of the pandemic experienced considerable levels of psychological distress at admission, with some improvements within 3 months after discharge.

Purpose: We aimed to determine incidence of hepatocellular carcinoma (HCC) and decompensated liver cirrhosis in persons with chronic hepatitis B virus (HBV) infection in Denmark stratified by disease phase, liver cirrhosis, and treatment status at baseline. Additionally, we aimed to assess the prognostic value of the PAGE-B HCC risk score in a mainly non-cirrhotic population. Patients and Methods: In this register-based cohort study, we included all individuals over the age of 18, with chronic HBV infection first registered between 2002 and 2016 in at least one of three nationwide registers. The study population was followed until HCC, decompensated liver cirrhosis, death, emigration, or December 31, 2017, which ever came first. Results: Among 6016 individuals included in the study, 10 individuals with and 23 without baseline liver cirrhosis developed HCC during a median follow up of 7.3 years (range 0.0– 15.5). This corresponded to five-year cumulative incidences of 7.1% (95% confidence interval (CI) 2.0– 12.3) and 0.2% (95% CI 0.1– 0.4) in persons with and without baseline liver cirrhosis. The five-year cumulative incidence of decompensated liver cirrhosis was 0.7% (95% CI 0.5– 1.0). Among 2038 evaluated for liver events stratified by disease phase, incidence of HCC was low in all who were non-cirrhotic and untreated for HBV at baseline. PAGE-B score was evaluated in 1529 persons. The 5-year cumulative incidence of HCC was 0, 0.8 (95% CI 0.5– 1.8), and 8.7 (95% CI 1.0– 16.4) in persons scoring < 10, 10– 17 and > 17, respectively (c-statistic 0.91 (95% CI 0.84– 0.98)). Conclusion: We found low incidence of HCC and decompensated liver cirrhosis in persons with chronic HBV infection in Denmark. Moreover, the PAGE-B score showed good accuracy for five-year risk of developing HCC in the population with chronic HBV infection in Denmark.

Objective: Data on the risk of ischemic heart disease (IHD) in patients with chronic hepatitis B virus (CHB) are conflicting. Our objective was to address the rate of IHD in patients with CHB compared with individuals without CHB (control-persons) from the general population. Study Design and Setting: We conducted a cohort study of prospectively obtained data from Danish nationwide registries. We produced cumulative incidence curves and calculated the unadjusted incidence rate ratio (IRR) of IHD in persons with and without CHB. The adjusted association between having CHB and developing IHD was examined using a cause-specific Cox regression model. Results: In total, 6472 persons with CHB and 62,251 age- and sex-matched individuals from the general population were followed for 48,840 and 567,456 person-years, respectively, during which 103 (1,59%) with CHB and 1058 (1,70%) control-persons developed IHD. The crude IRR was 1.13 (95% CI: 0.91– 1.39). CHB did not have a statistically significant effect on the rate of IHD after adjusting for several confounding factors (adjusted hazard ratio: 0.96, 95% CI: 0.76– 1.21). Conclusion: In this nationwide cohort study, we did not find any difference between rate of IHD in persons with CHB in comparison with the general population.