Beneficial effects of multi-disciplinary rehabilitation in postacute COVID-19: an observational cohort study.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic increases the demand for postacute care in patients after a severe disease course. Various long-term sequelae are expected and rehabilitation medicine is challenged to support physical and cognitive recovery. AIM: We aimed to explore the dysfunctions and outcome of COVID-19 survivors after early postacute rehabilitation. DESIGN: Observational cohort study. METHODS: This study evaluated the postacute sequelae of patients hospitalized for SARS-CoV-2 infection and analyzed rehabilitative outcomes of a subgroup of patients included in the prospective observational multicenter CovILD study. RESULTS: A total of 23 subjects discharged after severe to critical COVID-19 infection underwent an individualized, multiprofessional rehabilitation. At the start of postacute rehabilitation, impairment of pulmonary function (87%), symptoms related to postintensive care syndrome, and neuropsychological dysfunction (85%) were frequently found, whereas cardiac function appeared to be largely unaffected. Of interest, multi-disciplinary rehabilitation resulted in a significant improvement in lung function, as reflected by an increase of forced vital capacity (P=0.007) and forced expiratory volume in one second (P=0.014), total lung capacity (P=0.003), and diffusion capacity for carbon monoxide (P=0.002). Accordingly, physical performance status significantly improved as reflected by a mean increase of six-minute walking distance by 176 (SD±137) meters. Contrarily, a considerable proportion of patients still had limited diffusion capacity (83%) or neurological symptoms including peripheral neuropathy at the end of rehabilitation. CONCLUSIONS: Individuals discharged after a severe course of COVID-19 frequently present with persisting physical and cognitive dysfunctions after hospital discharge. Those patients significantly benefit from multi-disciplinary inpatient rehabilitation. CLINICAL REHABILITATION IMPACT: Our data demonstrated the highly promising effects of early postacute rehabilitation in survivors of severe or critical COVID-19. This findings urge further prospective evaluations and may impact future treatment and rehabilitation strategies.

Lemierre's syndrome following infectious mononucleosis.

We report the case of an 18-year-old woman who was admitted to the medical intensive care unit in Innsbruck with severe septic shock and respiratory insufficiency following a prolonged infection of the upper airways (pharyngitis, sinusitis). Abscessing pneumonia and bilateral pleural empyema were diagnosed as focus. Cultures of pleural fluids were positive for Fusobacterium necrophorum. In addition to multiple organ dysfunction syndrome (acute lung injury, acute renal failure, disseminated intravascular coagulation), she developed tenderness in the right neck followed by septic arthritis of the right sternoclavicular joint a few days later. Further history revealed a previous period of infectious mononucleosis (EBV infection). The previously healthy patient eventually made a complete recovery after prolonged treatment in the ICU including antibiotic therapy and multiple surgical interventions and drainage. Lemierre's syndrome is characterized by severe infection, with pharyngitis, sepsis and thrombosis of the internal jugular vein, and is most frequently associated with upper airway infection with Fusobacterium necrophorum, often preceded by infection with Epstein-Barr virus which enables bacteria growing in the oral cavity to invade.

Nramp1 functionality increases inducible nitric oxide synthase transcription via stimulation of IFN regulatory factor 1 expression.

Natural-resistance associated macrophage protein 1 (Nramp1) encodes a transmembrane phagolysosomal protein exerting resistance toward infections with intracellular pathogens by a mechanism not fully elucidated so far. We used the murine macrophage cell line RAW264.7, stably transfected with functional (RAW-37) or nonfunctional (RAW-21) Nramp1, to study for differences in the expression of NO, a central antimicrobial effector molecule of macrophages. Following stimulation with IFN-gamma and LPS, Nramp1-expressing cells exhibit higher enzymatic activity of inducible NO synthase (iNOS) and increased cytoplasmic iNOS mRNA levels than RAW-21 cells. Time-course experiments showed that iNOS-mRNA levels remain increased in RAW-37 cells after prolonged cytokine stimulation while they decrease in RAW-21 cells. Reporter gene assays with iNOS-promoter luciferase constructs demonstrated an increased and prolonged promoter activity in Nramp1-resistant vs susceptible cells. This was paralleled by increased IFN regulatory factor 1 (IRF-1) expression and binding affinity to the iNOS promoter in RAW-37 cells, which may be related to enhanced STAT-1 binding affinity in these cells. A point mutation within the IRF-1 binding site of the iNOS promoter abolished the differences in iNOS transcription between RAW-21 and RAW-37 cells. Cells carrying functional Nramp1 express increased amounts of NO, which may be related to STAT-1-mediated stimulation of IRF-1 expression with subsequent prolonged activation of iNOS transcription. Enhanced NO expression may partly underlie the protection against infection with intracellular pathogens by Nramp1 functionality.

Effect of iron treatment on circulating cytokine levels in ESRD patients receiving recombinant human erythropoietin.

BACKGROUND: Anemia in patients with end-stage renal disease (ESRD) is treated with recombinant human erythropoietin (rhEPO) often in combination with iron. However, iron catalyzes the formation of toxic radicals, which might promote vascular damage, is a nutrient for microorganisms, and negatively affects immune pathways, thus increasing the risk for severe infections. METHODS: We investigated 28 patients on chronic hemodialysis who were randomized to receive either rhEPO alone (N = 15) or rhEPO in combination with intravenous iron (N = 13) for a period of 12 weeks. We analyzed iron therapy associated changes in cytokine patterns and endogenous radical formation. RESULTS: Tumor necrosis factor-alpha (TNF-alpha) levels were increased in ESRD patients at study entry and then decreased significantly over time in subjects receiving additional iron, while they increased with rhEPO alone. In contrast, we found serum concentrations of the anti-inflammatory cytokine interleukin (IL)-4 to increase with iron therapy. A significant negative correlation between iron availability, as determined by transferrin saturation, and TNF-alpha levels (P = 0.008) and a positive one between transferring saturation and IL-4 (P = 0.02) pointed to the potential role of iron to induce immunologic changes. Interestingly, iron therapy resulted in a slight decrease in the amounts of endogenous peroxides, which may be referred to reduced TNF-alpha concentrations since peroxide concentrations were positively correlated to TNF-alpha levels (P = 0.046) and negatively to transferrin saturation (P = 0.02). CONCLUSION: Iron supplementation in ESRD patients down-regulates proinflammatory immune effector pathways and stimulates the expression of the anti-inflammatory cytokine IL-4. Such a condition is detrimental for host response toward invading pathogens. However, tissue damage by radicals such as endogenous peroxides may be reduced in this condition due to impaired TNF-alpha formation.