COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01–30.26]; p = 0.048) and mortality (OR 5.21 [1.06–25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.

The COVID-19 pandemic is caused by the SARS CoV-2 virus and can lead to severe lung damage and hyperinflammation. In the context of COVID-19 infection, inflammation-induced degradation of the glycocalyx layer in endothelial cells has been demonstrated. Syndecan-1 (SDC-1) is an established parameter for measuring glycocalyx injury. This prospective, multicenter, observational, cross-sectional study analyzed SDC-1 levels in 24 convalescent patients that had been infected with SARS-CoV-2 with mild disease course without need of hospitalization. We included 13 age-matched healthy individuals and 10 age-matched hospitalized COVID-19 patients with acute mild disease course as controls. In convalescent COVID-19 patients, significantly elevated SDC-1 levels were detected after a median of 88 days after symptom onset compared to healthy controls, whereas no difference was found when compared to SDC-1 levels of hospitalized patients undergoing acute disease. This study is the first to demonstrate signs of endothelial damage in non-pre-diseased, convalescent COVID-19 patients after mild disease progression without hospitalization. The data are consistent with studies showing evidence of persistent endothelial damage after severe or critical disease progression. Further work to investigate endothelial damage in convalescent COVID-19 patients should follow.

Background and Purpose: New therapies for inflammatory bowel disease (IBD) are highly desirable. As apolipoprotein (apo)A‐I mimetic peptides are beneficial in several animal models of inflammation, we hypothesized that they might be effective at inhibiting murine colitis.Experimental Approach: Daily injections of 5A peptide, a synthetic bihelical apoA‐I mimetic dissolved in PBS, or PBS alone were administered to C57BL/6 mice fed 3% (w v^‐1) dextran sodium sulfate (DSS) in drinking water or healthy controls.Key Results: Daily treatment with 5A peptide potently restricted DSS‐induced inflammation, as indicated by improved disease activity indices and colon histology, as well as decreased intestinal tissue myeloperoxidase levels and plasma TNFα and IL‐6 concentrations. Additionally, plasma levels of monocyte chemoattractant protein‐1 and the monocyte expression of adhesion‐mediating molecule CD11b were down‐regulated, pro‐inflammatory CD11b⁺/Ly6c^high monocytes were decreased, and the number of intestinal monocytes was reduced in 5A peptide‐treated animals as determined by intravital macrophage‐related peptide‐8/14‐directed fluorescence‐mediated tomography and post‐mortem immunhistochemical F4/80 staining. Intravital fluorescence microscopy of colonic microvasculature demonstrated inhibitory effects of 5A peptide on leukocyte adhesion accompanied by reduced plasma levels of the soluble adhesion molecule sICAM‐1. In vitro 5A peptide reduced monocyte adhesion and transmigration in TNFα‐stimulated monolayers of human intestinal microvascular endothelial cells. Increased susceptibility to DSS‐induced inflammation was noted in apoA‐I^−/− mice.Conclusions and Implications: The 5A peptide is effective at ameliorating murine colitis by preventing intestinal monocyte infiltration and activation. These findings point to apoA‐I mimetics as a potential treatment approach for IBD.

Background: The prone position (PP) is increasingly used in mechanically ventilated coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) patients. However, studies investigating the influence of the PP are currently lacking in these patients. This is the first study to investigate the influence of the PP on the oxygenation and decarboxylation in COVID-19 patients. Methods: A prospective bicentric study design was used, and in mechanically ventilated COVID-19 patients, PP was indicated from a partial pressure of oxygen in arterial blood (P_aO2)/fraction of inspired oxygen (F_IO2) ratio of <200. Patients were left prone for 16 h each. Pressure levels, F_IO2, were adjusted to ensure a P_aO2 greater than 60 mmHg. Blood gas analyses were performed before (baseline 0.5 h), during (1/2/5.5/9.5/13 h), and after being in the PP (1 h), the circulatory/ventilation parameters were continuously monitored, and lung compliance (LC) was roughly calculated. Responders were defined compared to the baseline value (P_aO2/F_IO2 ratio increase of ≥15%; partial pressure of carbon dioxide (P_aCO2) decrease of ≥2%). Results: 13 patients were included and 36 PP sessions were conducted. Overall, P_aO2/F_IO2 increased significantly in the PP (p < 0.001). Most P_aO2/F_IO2 responders (29/36 PP sessions, 77%) were identified 9.5 h after turning prone (14% slow responders), while most P_aCO2 responders (15/36 PP sessions, 42%) were identified 13 h after turning prone. A subgroup of patients (interval intubation to PP ≥3 days) showed less P_aO2/F_IO2 responders (16% vs. 77%). An increase in P_aCO2 and minute ventilation in the PP showed a significant negative correlation (p < 0.001). LC (median before the PP = 38 mL/cm H₂O; two patients with LC >80 mL/cm H₂O) showed a significant positive correlation with the 28 day survival of patients (p = 0.01). Conclusion: The PP significantly improves oxygenation in COVID-19 ARDS patients. The data suggest that they also benefit most from an early PP. A decrease in minute ventilation may result in fewer P_aCO2 responders. LC may be a predictive outcome parameter in COVID-19 patients. Trial registration: Retrospectively registered.

Severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. Vaccination is considered the core approach to containing the pandemic. There is currently insufficient evidence on the efficacy of these vaccines in immunosuppressed inflammatory bowel disease (IBD) patients. The aim of this study was to investigate the humoral response in immunosuppressed IBD patients after COVID-19 mRNA vaccination. In this prospective study, IgG antibody levels (AB) against the SARS-CoV-2 receptor-binding domain (spike-protein) were quantitatively determined. For assessing the potential neutralizing capacity, a SARS-CoV-2 surrogate neutralization test (sVNT) was employed in IBD patients (n = 95) and healthy controls (n = 38). Sera were examined prior to the first/second vaccination and 3/6 months after second vaccination. Patients showed lower sVNT (%) and IgG-S (AU/mL) AB both before the second vaccination (sVNT p < 0.001; AB p < 0.001) and 3 (sVNT p = 0.002; AB p = 0.001) and 6 months (sVNT p = 0.062; AB p = 0.061) after the second vaccination. Although seroconversion rates (sVNT, IgG-S) did not differ between the two groups 3 months after second vaccination, a significant difference was seen 6 months after second vaccination (sVNT p = 0.045). Before and three months after the second vaccination, patients treated with anti-tumor necrosis factor (TNF) agents showed significantly lower AB than healthy subjects. In conclusion, an early booster shot vaccination should be discussed for IBD patients on anti-TNF therapy.