ABSTRACT
Background: A number of histopathological reports showed the presence of widespread thrombosis and associated morphology in pulmonary vessels of patients with COVID-19. Later, we identified vascular occlusions with neutrophils and neutrophil extracellular traps (NETs), as major components, in autopsy tissue from patients with COVID-19.Methods: We, here investigated 109 lung specimens from 17 patients with COVID-19 and compared them with 11 lung specimens from two patients who succumbed to pulmonary embolism and acute cardiac. Healthy lung specimens from four patients served as controls. We studied these autopsy lung specimens using immunohistochemistry and native endogenous fluorescence.Findings: We present a label-free imaging technique using native endogenous fluorescence that enables the visualization of occluded vessels. We demonstrate that native endogenous fluorescence identified occluded vessels in tissue specimens from patients with COVID-19.Interpretation: Label-free detection of occluded vessels enabled the detection of affected occluded vessels in lung specimens of patients with COVID-19 where the occluding components showed varying contents of neutrophil-derived materials.Funding Statement: Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-StiftungDeclaration of Interests: All authors have no conflicts of interests to declare.Ethics Approval Statement: An institutional approval from each local Ethical Committee was obtained (permit #193_13B; permit # 174_20B; EK 092/20; EK 119/20; EK 460/20).
Subject(s)
COVID-19 , ThrombosisABSTRACT
Objective: To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods: Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results: Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions: In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.
Subject(s)
COVID-19ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. Here, we report that low plasma interleukin-3 (IL-3) levels were associated with increased severity and mortality during SARS-CoV-2 infections. IL-3 promoted the recruitment of antiviral circulating plasmacytoid dendritic cells (pDCs) into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells. This study identifies IL-3 as a predictive disease marker and potential therapeutic target for SARS-CoV-2 infections.Competing Interest StatementThe authors have declared no competing interest.View Full Text
Subject(s)
COVID-19ABSTRACT
Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observed a significantly reduced incidence of SARS-CoV-2 infection in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure. Hence, cytokine inhibitors seem to at least partially protect from SARS-CoV-2 infection.Authors David Simon and Koray Tascilar contributed equally to this work. Authors Markus F. Neurath and Georg Schett share senior authorship.