NK cells in self-limited HCV infection exhibit a more extensively differentiated, but not memory-like, repertoire.

Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings. By making use of a unique cohort of monitored, at-risk intravenous drug users in this study, we were able to dissect the phenotypic and functional parameters associated with NK cell differentiation and NK cell memory in patients 3 years after acute HCV infection and either the subsequent self-clearance or progression to chronicity. We observed increased expression of cytolytic mediators and markers CD56bright and NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection. Patients with a self-limited infection expressed higher levels of differentiation-associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively differentiated NK cell phenotype is associated with self-clearance in HCV patients, while the NK cells of chronic patients exhibited more naïve and effector NK cell phenotypic and functional characteristics. The identification of these distinct NK cell repertoires may shed light on the role NK cells play in determining the outcome of acute HCV infections, and the underlying immunological defects that lead to chronicity.

Coronary calcium score in COVID-19 survivors: Association with cardiac injury and cardiac function after 6 weeks.

Aims: Cardiac manifestations are common in COVID-19, often elevated serum troponin levels or myocardial dysfunction on trans-thoracic echocardiography (TTE) is observed. Both parameters are associated with increased in-hospital mortality. Possibly, subclinical coronary atherosclerosis plays a role, of which severity can be assessed by calculating the coronary artery calcium (CAC) score. This study aims to determine the relation between coronary atherosclerosis and cardiac manifestations in COVID-19 survivors. Methods: This study was conducted at the Leiden University Medical Center. All patients admitted for COVID-19 were included and scheduled for a 6-week follow-up visit with trans-thoracic echocardiography (TTE). CAC was assessed according to an ordinal score on non-gated, non-contrast enhanced computed tomography of the chest. Patients with and without CAC were compared on cardiac injury as reflected by elevated serum troponin levels and impaired cardiac function assessed through TTE. Results: In total, 146 patients were included. Mean age was 62 years and 62 % of the patients were male. During admission, patients with CAC showed significantly higher levels of troponin (19 ng/L vs 10 ng/L; p < 0.01). Overall, mild echocardiographic abnormalities were seen; 12 % showed reduced left ventricular function (left ventricular ejection fraction of <50 %) and 14 % reduced right ventricular function (tricuspid annular planar systolic excursion ≤17 mm). Following multivariable adjustments, there was no significant relation between CAC and myocardial function at 6 weeks. Conclusion: The present study shows that coronary atherosclerosis is associated with cardiac injury in COVID-19 survivors. However, no significant relation with impaired cardiac function was demonstrated.