Glucocorticoids (GC) are potent anti-inflammatory agents, broadly used to treat acute and chronic inflammatory diseases, e.g., critically ill COVID-19 patients or patients with chronic inflammatory bowel diseases. GC not only limit inflammation but also promote its resolution although the underlying mechanisms are obscure. Here, we reveal reciprocal regulation of 15-lipoxygenase (LOX) isoform expression in human monocyte/macrophage lineages by GC with respective consequences for the biosynthesis of specialized proresolving mediators (SPM) and their 15-LOX-derived monohydroxylated precursors (mono-15-OH). Dexamethasone robustly up-regulated pre-mRNA, mRNA, and protein levels of ALOX15B/15-LOX-2 in blood monocyte–derived macrophage (MDM) phenotypes, causing elevated SPM and mono-15-OH production in inflammatory cell types. In sharp contrast, dexamethasone blocked ALOX15/15-LOX-1 expression and impaired SPM formation in proresolving M2-MDM. These dexamethasone actions were mimicked by prednisolone and hydrocortisone but not by progesterone, and they were counteracted by the GC receptor (GR) antagonist RU486. Chromatin immunoprecipitation (ChIP) assays revealed robust GR recruitment to a putative enhancer region within intron 3 of the ALOX15B gene but not to the transcription start site. Knockdown of 15-LOX-2 in M1-MDM abolished GC-induced SPM formation and mono-15-OH production. Finally, ALOX15B/15-LOX-2 upregulation was evident in human monocytes from patients with GC-treated COVID-19 or patients with IBD. Our findings may explain the proresolving GC actions and offer opportunities for optimizing GC pharmacotherapy and proresolving mediator production.

Purpose: Some patients experience long-term sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, despite a present post-COVID condition, defined as “any symptom lasting longer than 12 weeks,” only a subset of patients search for medical help and therapy. Method: We invited all adults with a positive real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 between March 2020 and September 2021 (n = 4091) in the city of Jena to answer a standardized questionnaire including demographic information, the course of the acute infection and current health status. K-means-clustering of quality of life (QoL) was used to explore post-COVID subgroups. Results: A total of 909 participants at a median interval of 367 (IQR 291/403) days after acute infection were included in the analysis. Of those, 643 (70.7%) complained of having experienced persistent symptoms at the time of the survey. Cluster analysis based on QoL revealed two subgroups of people with persistent post-COVID symptoms. Whereas 189/643 participants (29.4%) showed markedly diminished QoL, normal QoL was detected in 454/643 individuals (70.6%). Conclusion: Despite persistent symptoms being reported by nearly three quarters of participants, only one-third of these described a significant reduction in QoL (cluster 1), whereas the other two-thirds reported a near-normal QoL (cluster 2), thus indicating a differentiation between “post-COVID disease” and “post-COVID condition”. The prevalence of clinically relevant post-COVID disease was at least 20.7%. Health policies should focus on this subset.

Introduction: Following SARS‐CoV‐2‐infection up to 21% of patients will develop post‐COVID‐syndrome. Autoantibodies (AAbs) targeting neuronal‐ß‐adrenergic and muscarinic receptors may provide crucial contributions to the pathophysiology of this condition. Immunoadsorption (IA) has been identified as an effective means of removing AAbs and has resulted in clinical improvements of other autoantibody‐associated diseases.Methods: We determined AAb‐levels (anti‐ß1/ß2 and anti‐M3/M4 receptor) in 178 patients diagnosed with post‐COVID‐syndrome and described the clinical courses of two patients with elevated AAb‐levels that underwent IA‐treatment.Results: AAbs were detected in 57% (101/178) of patients diagnosed with post‐COVID‐syndrome. Substantial reductions in AAb‐levels and clinical remission were achieved in one of two patients who was treated with IA. However, this patient relapsed within 6 weeks with a concomitant increase in AAb‐levels.Conclusion: Collectively, AAbs may play a pathophysiologic role in post‐COVID and their removal provide transient benefits in some patients. However, these findings should be further investigated in randomized‐controlled‐trials.

Zusammenfassung: Einleitung Persistierende und neu-auftretende Beschwerden nach einer SARS-CoV-2-Infektion (sog. Long/Post-COVID-Syndrom) stellen eine große Herausforderung für unser Gesundheitssystem dar. Analysen zu Bedürfnissen von Betroffenen an die primäre Behandlung und Versorgungsplanung sind rar, sodass die gezielte Lenkung von Patientenströmen und letztlich auch die Patientenversorgung deutlich erschwert ist. Methoden Die JenUP-Studie (Jenaer Untersuchung zum populations-basierten Auftreten von Post-COVID-Beschwerden) ist eine fragebogenbasierte Untersuchung aller Erwachsenen der Stadt Jena, welche zwischen März 2020 und September 2021 mit einer RT-PCR-bestätigte SARS-CoV-2-Infektion durch das Gesundheitsamt Jena registriert wurden. Ein Teil dieser Studie beschäftigt sich mit der ärztlichen Betreuung von Betroffenen mit prolongierten/persistierenden Symptomen sowie deren subjektiven Schwierigkeiten im Rahmen dieser Behandlung. Ergebnisse Insgesamt beantworten 1,008 der 4,209 angeschriebenen Personen den zugesendeten Fragebogen, wobei 922 (91,5%) über das Auftreten von mindestens einem Long/Post-COVID-assoziierten Symptom berichteten. 85,6% dieser Personen (790/922) gaben zudem detaillierte Auskünfte über Kontakte mit Einrichtungen und Personen des Gesundheitswesens. Drei von vier Personen (590/790) stellten sich im Zusammenhang mit ihren Beschwerden hausärztlich vor, 155/790 (19,6%) konsultierten, meist zusätzlich, Fachspezialist:innen (am häufigsten Internist:innen – 7,1% (55/790). Schwierigkeiten eine subjektiv benötigte Therapie zu erhalten, wurden von 22,6% (162/718) der Befragten angegeben. Als Gründe wurden vornehmlich das patientenseitige Gefühl scheinbar „nicht krank genug zu sein“ (69/162) und ein fehlender Ansprechpartner (65/162) angeführt. 27% (247/919) aller Probanden mit Long/Post-COVID-Beschwerden äußerten den Wunsch nach einem konkreten Ansprechpartner. Schlussfolgerung Die hausärztliche Betreuung stellt eine zentrale Säule der ambulanten Versorgung von Long/Post-COVID-Patienten dar. Zudem sollten gemäß der nationalen S1-Leitlinie flächendeckende Strukturen zur interdisziplinären Betreuung aufgebaut werden. Die Analyse wahrgenommener Barrieren bei der ärztlichen Betreuung und der Wünsche für die Versorgung stellen einen ersten Schritt zur Verbesserung der ambulanten Versorgung von Long/Post-COVID-Patienten dar.

Disseminated intravascular coagulation (DIC) is a systemic disease characterized by simultaneous thrombosis, bleeding, and partially excessive fibrinolysis. Systemic shock, trauma, bacterial toxins, and procoagulants-expressing solid and hematologic malignancies are common causes of this life-threatening hemorrhagic complication and often require treatment in intensive care units. We describe a case of an elderly man with recurrent severe bleeding events in the cause of DIC, including epistaxis, hemoptysis, hematuria, and gastrointestinal bleeding. Laboratory investigations revealed elevated prostate-specific antigen (PSA), suggesting an underlying prostate cancer. Despite intensified coagulatory therapy, the coagulation disorder could not be stabilized. A single injection of degarelix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, led to rapid stabilization of the coagulation and decreased PSA within days. One year after initiating androgen-deprivation therapy, there were recurrent transfusion-requiring bleeding events, and a concomitant PSA increase occurred, suggesting metastatic castration-resistant disease associated with DIC. This case emphasizes DIC as a possible primary phenomenon and indicator for the progression of the underlying malignancy, as well as the importance of etiological therapies in the management of DIC.