Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: Results from the COViK study (preprint)

Purpose: COViK - a prospective hospital-based multicenter case-control study in Germany - aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. Methods: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. Results: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95% CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. Conclusion: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.

Recruitment of plasma cells to the bone marrow in primary and secondary immune reactions (preprint)

Bone marrow plasma cells (BMPC) emerge as a consequence of immune reactions and are considered the source of antibodies that protect against recurrent infectious diseases throughout life. Despite their importance, it remains unclear if these cells reflect different activation environments or the differentiation/maturation stages of their precursors. Here we track the recruitment of plasma cells, generated in primary and secondary immune reactions to SARS-CoV-2 spike protein vaccines, to the human bone marrow. Trajectories based on single cell transcriptomes and antigen-receptor clonotypes of antibody-secreting cells exiting the immune reaction and of those residing in the bone marrow, allow to follow the evolution of the immune response to these vaccines, leading to sequential colonization of these cells to different compartments (clans) of BMPC, and their establishment as long-lived (memory) plasma cells. In primary immune reactions, both CD19low (clans 1 and 4) and CD19high (clan 0) BMPC are generated. In secondary immune reactions, mostly CD19high BMPC of the largest compartment (clan 0) are generated, resulting from the reactivation of memory B lymphocytes. The latter is also observed in vaccinated convalescent individuals and upon recall vaccination against diphtheria/tetanus/pertussis (DTP). Thus, humoral immunological memory, i.e. serum antibodies secreted by long-lived memory BMPC, is generated already in the primary immune response, more so in the secondary, and it represents the evolution of the immune response.

Effectiveness of vaccines in preventing hospitalization due to COVID-19: A multicenter hospital-based case-control study, Germany, June 2021 to January 2022 (preprint)

We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization (Delta-variant dominance). Two-dose VE was 89% (95%CI 84-93%) overall, 79% in patients with >2 comorbidities and 77% in adults aged 60-75 years. A third dose increased VE to >93% in all patient-subgroups.