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IntroductionProgression of fibrotic interstitial lung disease (ILD) leads to irreversible loss of lung function and increased mortality. Based on an institutional ILD registry, we aimed to evaluate biomarkers derived from baseline patient characteristics, computed tomography (CT), and peripheral blood for prognosis of disease progression in fibrotic ILD patients.MethodsOf 209 subsequent ILD-board patients enregistered, 142 had complete follow-up information and were classified fibrotic ILD as defined by presence of reticulation or honeycombing using a standardized semi-quantitative CT evaluation, adding up typical ILD findings in 0–6 defined lung fields. Progression at 1 year was defined as relative loss of ≥10% in forced vital capacity, of ≥15% in diffusion capacity for carbon monoxide, death, or lung transplant. Two-thirds of the patients were randomly assigned to a derivation cohort evaluated for the impact of age, sex, baseline lung function, CT finding scores, and blood biomarkers on disease progression. Significant variables were included into a regression model, its results were used to derive a progression-risk score which was then applied to the validation cohort.ResultsIn the derivation cohort, age, monocyte count ≥0.65 G/L, honeycombing and traction bronchiectasis extent had significant impact. Multivariate analyses revealed the variables monocyte count ≥0.65 G/L (1 point) and combined honeycombing or traction bronchiectasis score [0 vs. 1–4 (1 point) vs. 5–6 lung fields (2 points)] as significant, so these were used for score development. In the derivation cohort, resulting scores of 0, 1, 2, and 3 accounted for 1-year progression rates of 20, 25, 46.9, and 88.9%, respectively. Similarly, in the validation cohort, progression at 1 year occurred in 0, 23.8, 53.9, and 62.5%, respectively. A score ≥2 showed 70.6% sensitivity and 67.9% specificity, receiver operating characteristic analysis for the scoring model had an area under the curve of 71.7%.ConclusionThe extent of honeycombing and traction bronchiectasis, as well as elevated blood monocyte count predicted progression within 1 year in fibrotic ILD patients.

Summary: Background: In recent months numerous health care professional acquired COVID-19 at the workplace resulting in significant shortages in medical and nursing staff. We investigated how prior COVID-19 affects SARS-CoV-2 vaccination and how such knowledge could facilitate frugal vaccination strategies. Methods: In a cohort of 41 healthcare professionals with (n=14) and without (n=27) previous SARS-CoV-2 infection, we assessed the immune status before, during and after vaccination with BNT162b2. The humoral immune response was assessed by receptor binding domain ELISA and different SARS-CoV-2 neutralisation assays using wildtype and pseudo-typed viruses. T cell immunity against SARS-CoV-2 surface and nucleocapsid peptides were studied using interferon-γ release assays and intracellular flow cytometry. Vaccine-related side effects were captured. Findings: Prior COVID-19 resulted in improved vaccine responses both in the B and T cell compartment. In vaccine recipients with prior COVID-19, the first vaccine dose induced high antibody concentrations comparable to seronegative vaccine recipients after two injections. This translated into more efficient neutralisation of virus particles, even more pronounced than expected from the RBD ELISA results. Furthermore, T cell responses were stronger in convalescents and particularly strong against the SARS-CoV-2 nucleocapsid protein. Interpretation: Herein, we corroborate recent findings suggesting that in convalescents a single vaccine dose is sufficient to boost adequate in vitro neutralisation of SARS-CoV-2 and therefore may be sufficient to induce adequate protection against severe COVID-19. New spike mutated virus variants render the highly conserved nucleocapsid protein – eliciting strong SARS-CoV-2 specific T cell immunity – an interesting additional vaccine target. Funding: Christian Doppler Research Association, Johannes Kepler University Linz