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1.
Preprint in English | Other preprints | ID: ppcovidwho-294933

ABSTRACT

Objective to assess reactogenicity and immunogenicity of heterologous prime-boost immunisations of ChAdOx1-nCoV19 (Vaxzevria, ChAdOx) followed by BNT162b2 (Comirnaty, BNT) compared to homologous BNT/BNT immunisation. Design prospective, observational cohort study. Setting unicenter study in a cohort of health care workers at a tertiary care center in Berlin, Germany. Participants 340 health care workers immunised between 27 December 2020 and 21 May 2021 at Charité - Universitätsmedizin Berlin, Germany Main outcome measures the main outcomes were reactogenicity assessed on days one, three, five and seven post prime and boost vaccination, and immunogenicity measured by serum SARS-CoV-2 full spike-, spike S1-, and spike RBD-IgG, virus neutralisation capacity, anti-S1-IgG avidity, and T cell reactivity measured by Interferon gamma release assay at 3-4 weeks post prime and boost immunisation. Results Heterologous ChAdOx/BNT booster vaccination was overall well-tolerated and reactogenicity was largely comparable to homologous BNT/BNT vaccination. Systemic reactions were most frequent after prime immunisation with ChAdOx (86%, 95CI: 79-91), and less frequent after homologous BNT/BNT (65%, 95CI: 56-72), or heterologous ChAdOx/BNT booster vaccination (48%, 95CI: 36-59). Serum antibody responses and T cell reactivity were strongly increased after both homologous and heterologous boost, and immunogenicity was overall robust, and comparable between both regimens in this cohort, with slightly increased S1-IgG avidity and T cell responses following heterologous booster immunisation. Conclusions Evidence of rare thrombotic events associated with ChAdOx has led to recommendation of a heterologous booster with mRNA vaccines for certain age groups in several European countries, despite a lack of robust safety and immunogenicity data for this vaccine regimen. This interim analysis provides evidence that the currently recommended heterologous ChAdOx/BNT immunisation regimen with 10-12 week vaccine intervals is well tolerated and slightly more immunogenic compared to homologous BNT/BNT vaccination with three week vaccine intervals. Heterologous prime-boost immunisation for COVID-19 may be generally applicable to optimise logistics and improve immunogenicity and to mitigate potential intermittent supply shortages for individual vaccines.

2.
Cell ; 184(26): 6243-6261.e27, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1536467

ABSTRACT

COVID-19-induced "acute respiratory distress syndrome" (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyze pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single-cell genomics, immunohistology, and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS.


Subject(s)
COVID-19/pathology , COVID-19/virology , Idiopathic Pulmonary Fibrosis/pathology , Idiopathic Pulmonary Fibrosis/virology , Macrophages/pathology , Macrophages/virology , SARS-CoV-2/physiology , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , COVID-19/diagnostic imaging , Cell Communication , Cohort Studies , Fibroblasts/pathology , Gene Expression Regulation , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/genetics , Mesenchymal Stem Cells/pathology , Phenotype , Proteome/metabolism , Receptors, Cell Surface/metabolism , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Tomography, X-Ray Computed , Transcription, Genetic
3.
Emerg Infect Dis ; 27(8): 2174-2178, 2021 08.
Article in English | MEDLINE | ID: covidwho-1261342

ABSTRACT

We detected delayed and reduced antibody and T-cell responses after BNT162b2 vaccination in 71 elderly persons (median age 81 years) compared with 123 healthcare workers (median age 34 years) in Germany. These data emphasize that nonpharmaceutical interventions for coronavirus disease remain crucial and that additional immunizations for the elderly might become necessary.


Subject(s)
COVID-19 , Adult , Aged , Aged, 80 and over , COVID-19 Vaccines , Germany/epidemiology , Humans , SARS-CoV-2 , T-Lymphocytes , Vaccination
4.
Emerg Infect Dis ; 27(8): 2169-2173, 2021 08.
Article in English | MEDLINE | ID: covidwho-1261341

ABSTRACT

One week after second vaccinations were administered, an outbreak of B.1.1.7 lineage severe acute respiratory syndrome coronavirus 2 infections occurred in a long-term care facility in Berlin, Germany, affecting 16/20 vaccinated and 4/4 unvaccinated residents. Despite considerable viral loads, vaccinated residents experienced mild symptoms and faster time to negative test results.


Subject(s)
COVID-19 , SARS-CoV-2 , Berlin , Disease Outbreaks , Germany/epidemiology , Humans , Long-Term Care , Vaccination
5.
Cell ; 182(6): 1419-1440.e23, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-694631

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.


Subject(s)
Coronavirus Infections/immunology , Myeloid Cells/immunology , Myelopoiesis , Pneumonia, Viral/immunology , Adult , Aged , CD11 Antigens/genetics , CD11 Antigens/metabolism , COVID-19 , Cells, Cultured , Coronavirus Infections/blood , Coronavirus Infections/pathology , Female , HLA-DR Antigens/genetics , HLA-DR Antigens/metabolism , Humans , Male , Middle Aged , Myeloid Cells/cytology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Proteome/genetics , Proteome/metabolism , Proteomics , Single-Cell Analysis
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