A prospective clinical study on the mechanisms underlying critical illness myopathy-A time-course approach.

BACKGROUND: Critical illness myopathy (CIM) is a consequence of modern critical care resulting in general muscle wasting and paralyses of all limb and trunk muscles, resulting in prolonged weaning from the ventilator, intensive care unit (ICU) treatment and rehabilitation. CIM is associated with severe morbidity/mortality and significant negative socioeconomic consequences, which has become increasingly evident during the current COVID-19 pandemic, but underlying mechanisms remain elusive. METHODS: Ten neuro-ICU patients exposed to long-term controlled mechanical ventilation were followed with repeated muscle biopsies, electrophysiology and plasma collection three times per week for up to 12 days. Single muscle fibre contractile recordings were conducted on the first and final biopsy, and a multiomics approach was taken to analyse gene and protein expression in muscle and plasma at all collection time points. RESULTS: (i) A progressive preferential myosin loss, the hallmark of CIM, was observed in all neuro-ICU patients during the observation period (myosin:actin ratio decreased from 2.0 in the first to 0.9 in the final biopsy, P < 0.001). The myosin loss was coupled to a general transcriptional downregulation of myofibrillar proteins (P < 0.05; absolute fold change >2) and activation of protein degradation pathways (false discovery rate [FDR] <0.1), resulting in significant muscle fibre atrophy and loss in force generation capacity, which declined >65% during the 12 day observation period (muscle fibre cross-sectional area [CSA] and maximum single muscle fibre force normalized to CSA [specific force] declined 30% [P < 0.007] and 50% [P < 0.0001], respectively). (ii) Membrane excitability was not affected as indicated by the maintained compound muscle action potential amplitude upon supramaximal stimulation of upper and lower extremity motor nerves. (iii) Analyses of plasma revealed early activation of inflammatory and proinflammatory pathways (FDR < 0.1), as well as a redistribution of zinc ions from plasma. CONCLUSIONS: The mechanical ventilation-induced lung injury with release of cytokines/chemokines and the complete mechanical silencing uniquely observed in immobilized ICU patients affecting skeletal muscle gene/protein expression are forwarded as the dominant factors triggering CIM.

Predictors of post-COVID-19 and the impact of persistent symptoms in non-hospitalized patients 12 months after COVID-19, with a focus on work ability.

Background: Better knowledge of long-term symptoms following coronavirus disease 2019 (COVID-19), the so-called post-COVID-19, in non-hospitalized patients is needed. The aim of this study was to study persisent symptoms up to 12 months after COVID-19 in non-hospitalized patients and their impact on work ability. We also investigated predictors of persistent symptoms. Methods: This study encompassed non-hospitalized adult subjects with a COVID-19 infection confirmed via positive nasopharyngeal swab polymerase chain reaction test during the first wave of the pandemic in Uppsala, Sweden. In total, 566 subjects were sent a survey via e-mail or post with an invitation to participate in the survey 12 months post-diagnosis. The majority of subjects were healthcare workers, as this group was prioritized for testing. Results: A total of 366 subjects responded, with 47% reporting persistent symptoms 12 months after their COVID-19 diagnosis. The most commonly reported symptoms at this time were impaired sense of smell and/or taste and fatigue. Among the predictors of persistent symptoms were being born abroad, lower physical fitness compared with peers before COVID-19, body mass index >25 kg/m2, cooccurrence of hypertension and chronic pain, and having more than seven of the general COVID-19 symptoms at the onset. Respondents with symptoms after 12 months self-reported negatively about their general health and work ability. Conclusions: This study indicated that many people who had mild COVID-19 might have a variety of long-term symptoms. It highlights the importance of considering work ability after mild COVID-19.

Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid.

Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.