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Background Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there is little data on possible IgA-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and if IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome (APS), our approach focused on antiphospholipid antibodies (aPL). Methods In this retrospective cohort study clinical data and aPL from 64 patients with COVID-19 were compared from three independent tertiary hospitals (one in Liechtenstein, two in Switzerland). Samples were collected from April 9 th to May 1 st, 2020. Results Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID) (41%), a discovery cohort with severe illness (sdCOVID) (22%) and a confirmation cohort with severe illness (scCOVID) (38%). Total IgA, IgG and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P=0.01; scCOVID, p-value<0.001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anti-Cardiolipin IgA (sdCOVID and scCOVID, p-value<0.001), anti-Cardiolipin IgM (sdCOVID, P=0.003; scCOVID, P<0.001), and anti-Beta2 Glycoprotein-1 IgA (sdCOVID and scCOVID, P<0.001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. Conclusions Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA-response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.

AIMS OF THE STUDY: An extracorporeal membrane oxygenation system (ECMO), as a bridge to either recovery, a ventricular assist device (VAD), or heart or lung transplantation, may be the only lifesaving option for critically ill patients suffering from refractory cardiac, respiratory or combined cardiopulmonary failure. As peripheral hospitals may not offer ECMO treatment, tertiary care centres provide specialised ECMO teams for on-site implantation and subsequent patient transfer on ECMO to the tertiary hospital. This study reports the results of the largest ECMO transportation programme in Switzerland and describes its feasibility and safety. METHODS: Patients transported on ECMO by our mobile ECMO team to our tertiary centre between 1 September 2009 and 31 December, 2016 underwent retrospective analysis. Implantation was performed by our specialised ECMO team (primary transport) or by the medical staff of the referring hospital (secondary transport) with subsequent transfer to our institution. Type of ECMO, transport data, patient baseline characteristics, operative variables and postoperative outcomes including complications and mortality were collected from medical records. RESULTS: Fifty-eight patients were included (three patients excluded: one repatriation, two with incomplete medical records). Thirty-five patients (60%) received veno-venous, 22 (38%) veno-arterial and one patient (2%) veno-venoarterial ECMO. Forty-nine (84%) patients underwent primary and nine (16%) secondary transport. Thirty-five (60%) patients were transferred by helicopter and 23 (40%) by ambulance, with median distances of 38.1 (13-225) km and 21 (3-71) km respectively. No clinical or technical complications occurred during transportation. During hospitalisation, three patients had ECMO-associated complications (two compartment syndrome of lower limb, one haemothorax after central ECMO up-grade). Median days on ECMO was 8 (<1-49) and median days in hospital was 17 (<1-122). ECMO weaning was successful in 41 patients (71%), on-transport survival was 100%, 40 patients survived to discharge (69%), and overall survival was 67% (39 patients) at a median follow-up of 58 days (<1-1441). Cumulative survival was significantly affected by cardiogenic shock vs. ARDS (p = 0.001), veno-arterial and veno-venoarterial vs. veno-venous EC-MO (p = 0.001) and after secondary vs. primary transport (p <0.001). The ECMO weaning rate was significantly lower after secondary transfer (22%, two patients, both vaEC-MO) vs. primary transfer (80%, p = 0.002, 39 patients of which 35 (71%) had vvECMO). CONCLUSIONS:The first results of our ECMO transportation programme show its feasibility, safety and efficacy without on-site implant or on-transport complications or mortality. The favourable early survival may justify the large effort with respect to logistics, costs and manpower. With rising awareness, referring centres may increasingly consider this lifesaving option at an early stage, which may further improve outcomes.

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The clear reduction in disease severity in IVIG-treated mice and inhibition of virulence factor activity in mouse and human sera suggest that IVIG may be beneficial in invasive group A Streptococcus infections such as NF in addition to streptococcal toxic shock syndrome.

Background Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis – PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. Methods In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. Results In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. Conclusions In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.

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Background:Modic type 1 changes (MC1) are vertebral bone marrow (BM) edema that associate with non-specific low back pain (LBP). Two etiologies have been described. In the infectious etiology the anaerobic aerotolerant Cutibacterium acnes (C. acnes) invades damaged intervertebral discs (IVDs) resulting in disc infection and endplate damage, which leads to the evocation of an immune response. In the autoinflammatory etiology disc and endplate damage lead to the exposure of immune privileged disc cells and matrix to leukocytes, thereby evoking an immune response in the BM. Different etiologies require different treatment strategies. However, it is unknown if etiology-specific pathological mechanisms exist.Objectives:The aim of this study was to identify etiology-specific dysregulated pathways of MC1 and to perform in-depth analysis of immune cell populations of the autoinflammatory etiology.Methods:BM aspirates and biopsies were obtained from LBP patients with MC1 undergoing spinal fusion. Aspirates/biopsies were taken prior screw insertion through the pedicle screw trajectory. From each patient, a MC1 and an intra-patient control aspiration/biopsy from the adjacent vertebral level was taken. If C. acnes in IVDs adjacent to MC1 were detected by anaerobic bacterial culture, patients were assigned to the infectious, otherwise to the autoinflammatory etiology.Total RNA was isolated from aspirates and sequenced (Novaseq) (infectious n=3 + 3, autoinflammatory n=5 + 5). Genes were considered as differentially expressed (DEG) if p-value < 0.01 and log2fc > ± 0.5. Gene ontology (GO) enrichment was performed in R (GOseq), gene set enrichment analysis (GSEA) with GSEA software.Changes in cell populations of the autoinflammatory etiology were analyzed with single cell RNA sequencing (scRNAseq): Control and MC1 biopsies (n=1 + 1) were digested, CD45+CD66b- mononuclear cells isolated with fluorescence activated cell sorting (FACS), and 10000 cells were sequenced (10x Genomics). Seurat R toolkit was used for quality-control, clustering, and differential expression analysis.Transcriptomic changes (n=5 + 5) of CD45+CD66b+ neutrophils isolated with flow cytometry from aspirates were analyzed as for total bulk RNAseq. Neutrophil activation (n=3 + 3) was measured as CD66b+ expression with flow cytometry. CD66bhigh and CD66blow fractions in MC1 and control neutrophils were compared with paired t-test.Results:Comparing MC1 to control in total bulk RNAseq, 204 DEG in the autoinflammatory and 444 DEG in the infectious etiology were identified with only 67 shared genes (Fig. 1a). GO enrichment revealed “T-cell activation” (p = 2.50E-03) in the autoinflammatory and “complement activation, classical pathway” (p=1.1E-25) in the infectious etiology as top enriched upregulated biological processes (BP) (Fig 1b). ScRNAseq of autoinflammatory MC1 showed an overrepresentation of T-cells (p= 1.00E-34, OR=1.54) and myelocytes (neutrophil progenitor cells) (p=4.00E-05, OR=2.27) indicating an increased demand of these cells (Fig. 1c). Bulk RNAseq analysis of neutrophils from the autoinflammatory etiology revealed an activated, pro-inflammatory phenotype (Fig 1d), which was confirmed with more CD66bhigh neutrophils in MC1 (+11.13 ± 2.71%, p=0.02) (Fig. 1e).Figure 1.(a) Venn diagram of DEG from total bulk RNAseq (b) Top enriched upregulated BP of autoinflammatory (left) and infectious (right) etiology (c) Cell clustering of autoinflammatory MC1 BM (d) Enrichment of “inflammatory response” gene set in autoinflammatory MC1 neutrophils (e) Representative histogram of CD66b+ expression in MC1 and control neutrophils.Conclusion:Autoinflammatory and infectious etiologies of MC1 have different pathological mechanisms. T-cell and neutrophil activation seem to be important in the autoinflammatory etiology. This has clinical implication as it could be explored for diagnostic approaches to distinguish the two MC1 etiologies and supports developing targeted treatments for both etiologies.Disclosure of Interests:None declared