Evaluation of Humoral and Cellular Responses in SARS-CoV-2 mRNA Vaccinated Immunocompromised Patients.

Background: Immunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients. Methods: Five clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination. Results: All healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens. Conclusion: Patients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2.

Novel non-cystic features of polycystic kidney disease: having new eyes or seeking new landscapes.

For decades, researchers have been trying to decipher the complex pathophysiology of autosomal dominant polycystic kidney disease (ADPKD). So far these efforts have led to clinical trials with different candidate treatments, with tolvaptan being the only molecule that has gained approval for this indication. As end-stage kidney disease due to ADPKD has a substantial impact on health expenditures worldwide, it is likely that new drugs targeting kidney function will be developed. On the other hand, recent clinical observations and experimental data, including PKD knockout models in various cell types, have revealed unexpected involvement of many other organs and cell systems of variable severity. These novel non-cystic features, some of which, such as lymphopenia and an increased risk to develop infections, should be validated or further explored and might open new avenues for better risk stratification and a more tailored approach. New insights into the aberrant pathways involved with abnormal expression of PKD gene products polycystin-1 and -2 could, for instance, lead to a more directed approach towards early-onset endothelial dysfunction and subsequent cardiovascular disease. Furthermore, a better understanding of cellular pathways in PKD that can explain the propensity to develop certain types of cancer can guide post-transplant immunosuppressive and prophylactic strategies. In the following review article we will systematically discuss recently discovered non-cystic features of PKD and not well-established characteristics. Overall, this knowledge could enable us to improve the outcome of PKD patients apart from ongoing efforts to slow down cyst growth and attenuate kidney function decline.