No abstract

SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

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Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection, without neuroinvasion, and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

Introduction: One of the noted features of COVID-19 is the spectrum of expressivity in symptoms among those with the disease, ranging from no or mild symptoms that may last a small number of days, to severe and/or longer lasting symptoms. It is emerging that many patients have long lasting symptoms, several months after initial infection with COVID-19. The aim of this research was to characterize post-acute COVID-19 syndrome (PACS). Methods: This was a retrospective cross-sectional observational study. Participants were patients recovering from COVID-19 infection, enrolled in Mount Sinai Hospital′s COVID-19 Precision Recovery Program (PRP). Inclusion criteria were confirmed or probable (based on World Health Organization criteria) initial diagnosis of COVID-19; post-acute COVID-19 syndrome (defined as experiencing symptoms > 6 weeks since acute symptom onset) and being currently enrolled in the PRP during the months of July and August 2020. Study survey data were collected using REDCap. Demographic data, COVID-19 clinical data and patient-reported outcomes for breathlessness (Medical Research Council Breathlessness Scale), fatigue and quality of life (EuroQoL 5D-5L) were collected. Results: 84 individuals with PACS were included. Symptoms persisted at mean (range) 151 (54 to 255) days. The most prevalent persistent symptoms were fatigue (92%), loss of concentration/memory (74%), weakness (68%), headache (65%) and dizziness (64%). Most participants reported increased levels of disability associated with breathlessness, increased fatigue and reduced quality of life. Conclusions: Persistent symptoms following COVID-19 infection are prevalent, debilitating and appear to affect individuals regardless of acute infection severity or prior health status. More detailed research is required in order to identify specific symptom clusters associated with PACS, and to devise effective interventional strategies.

N/A - Letter to the Editor

Post-acute COVID-19 syndrome (PACS) is a collection of persistent and debilitating symptoms lasting weeks to months after acute COVID-19 infection, with fatigue most commonly reported. There is controversy surrounding the role of exercise programs for this condition, due to concerns over the potential to worsen fatigue. We developed a novel physical therapy program known as Autonomic Conditioning Therapy (ACT) for PACS, and report on the preliminary patient-reported outcome (PRO) data from individuals who completed ACT for PACS, compared with those who did not. Seventy-eight (55 [71%] female, median [range] age 43 [12 to 78]) met the inclusion criteria and consented to have their data included in the analyses. A total of 31 (40%) individuals completed ACT for PACS. There was within-group improvement in fatigue in individuals who completed ACT for PACS (mean difference [95% CI] -14 [-27 to -1], p = 0.03), as well as greater between-group impression of change measured on the Patient Global Impression of Change scale (ACT for PACS median [range] 5 [1 to 7], no ACT for PACS 4 [1 to 7], p < 0.01). ACT for PACS is a novel physical therapy program that can reduce fatigue in individuals with PACS.

Purpose of Review Stroke is the leading cause of permanent motor disability in the United States (US), but there has been little progress in developing novel, effective strategies for treating post-stroke motor deficits. The past decade has seen the rapid development of many promising, gamified neurorehabilitation technologies; however, clinical adoption remains limited. The purpose of this review is to evaluate the recent literature surrounding the adoption and use of gamification in neurorehabilitation after stroke. Recent Findings Gamification of neurorehabilitation protocols is both feasible and effective. Deployment strategies and scalability need to be addressed with more rigor. Relationship between engaged time on task and rehabilitation outcomes should be explored further as it may create benefits beyond repetitive movement. Summary As gamification becomes a more common and feasible way of delivering exercise-based therapies, additional benefits of gamification are emerging. In spite of this, questions still exist about scalability and widespread clinical adoption.