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In metabolic glycoengineering (MGE), cells or animals are treated with unnatural derivatives of monosaccharides. After entering the cytosol, these sugar analogues are metabolized and subsequently expressed on newly synthesized glycoconjugates. The feasibility of MGE was first discovered for sialylated glycans, by using N-acyl-modified mannosamines as precursor molecules for unnatural sialic acids. Prerequisite is the promiscuity of the enzymes of the Roseman-Warren biosynthetic pathway. These enzymes were shown to tolerate specific modifications of the N-acyl side chain of mannosamine analogues, for example, elongation by one or more methylene groups (aliphatic modifications) or by insertion of reactive groups (bioorthogonal modifications). Unnatural sialic acids are incorporated into glycoconjugates of cells and organs. MGE has intriguing biological consequences for treated cells (aliphatic MGE) and offers the opportunity to visualize the topography and dynamics of sialylated glycans in vitro, ex vivo, and in vivo (bioorthogonal MGE).

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DCs) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute illness to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage−HLADR+ cells lacking DC markers. Increased frequency of CD163+ CD14+ cells within the recently discovered DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of programmed death-ligand 1 (PD-L1) in conventional DCs (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.

The importance of pre-existing immune responses to seasonal endemic coronaviruses (HCoVs) for the susceptibility to SARS-CoV-2 infection and the course of COVID-19 is subject of an ongoing scientific debate. Recent studies postulate that immune responses to previous HCoV infections can either have a slightly protective or no effect on SARS-CoV-2 pathogenesis and, consequently, be neglected for COVID-19 risk stratification. Challenging this notion, we provide evidence that pre-existing, anti-nucleocapsid antibodies against endemic α-coronaviruses and S2 domain-specific anti-spike antibodies against β-coronavirus HCoV-OC43 are elevated in patients with COVID-19 compared to pre-pandemic donors. This finding is particularly pronounced in males and in critically ill patients. Longitudinal evaluation reveals that antibody cross-reactivity or polyclonal stimulation by SARS-CoV-2 infection are unlikely to be confounders. Thus, specific pre-existing immunity to seasonal coronaviruses may increase susceptibility to SARS-CoV-2 and predispose individuals to an adverse COVID-19 outcome, guiding risk management and supporting the development of universal coronavirus vaccines.

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Background: Human Siglec-1 mediates HIV trans-infection by interaction with virion-associated sialylated gangliosides. Results: Here, Siglec-1 on mouse macrophages mediated trans-infection of surface-bound MLV. This could be inhibited by biosynthetic modification of sialic acids' N-acyl side chain in virus-producer cells. Conclusion:The N-acyl side chain is a critical determinant of Siglec-1-dependent MLV trans-infection. Significance: Glycoengineering allows manipulation of sialic acid-dependent virus/receptor interactions.

Background: Inhibitors of cellular sialic acid expression offer substantial therapeutic promise for diseases associated with oversialylation. Results: 2-Acetylamino-2-deoxy-3-O-methyl-D-mannose reduces the sialic acid concentration in cells and inhibits the UDP-GlcNAc-2-epimerase/ManNAc kinase. Conclusion: Inhibition of the key enzyme of sialic acid biosynthesis by a ManNAc analog decreases cellular sialic acid expression. Significance: ManNAc analogs represent a new class of sialic acid inhibitors.

Background High infection rates among health care personnel in an uncontained pandemic can paralyze health systems due to staff shortages. Risk constellations and rates of seroconversion for health care workers during the first wave of the SARS-CoV-2 pandemic are still largely unclear. Methods Health care personnel (n=300) on different organizational units in the LMU Munich University Hospital were included and followed in this prospective longitudinal study in the period of March 24 until July 7, 2020. Participants were monitored in intervals of two to six weeks using different antibody assays for serological testing and questionnaires to evaluate risk contacts. In a subgroup of infected participants, we obtained nasopharyngeal swabs to perform whole genome sequencing for outbreak characterization. Results Health care workers involved in patient care on dedicated COVID-19 wards or on regular non-COVID-19 wards showed a higher rate of SARS-CoV-2 seroconversion compared to staff in the emergency department and non-frontline personnel. The landscape of risk contacts in these units was dynamic, with a decrease of unprotected risk contacts in the emergency department and an increase on non-COVID-19 wards. Both, the intensity and number of risk contacts, were associated with higher rates of seroconversion. On regular wards, staff infections tended to occur in clusters, while infections on COVID-19 wards were less frequent and apparently independent of each other. Conclusion The risk of SARS-CoV-2 infection for front-line health care workers was increased during the first pandemic wave in Southern Germany. Stringent measures for infection control are essential to protect all patient-facing staff during the ongoing pandemic.