Abstract
Background
Fatigue is the most prevalent and debilitating long-COVID (coronavirus disease) symptom; however, risk factors and pathophysiology of this condition remain unknown. We assessed ...risk factors for long-COVID fatigue and explored its possible pathophysiology.
Methods
This was a nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long-COVID fatigue.
Results
A total of 141 individuals were included. The mean age was 47 (SD: 13) years; 115 (82%) were recovering from mild coronavirus disease 2019 (COVID-19). Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long-COVID fatigue. They had a significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness, higher proportions of long-COVID symptoms, and of physical limitation in daily activities. Individuals with long-COVID fatigue also had poorer sleep quality and higher degree of depression. They had significantly lower heart rate 153.52 (22.64) vs 163.52 (18.53); P = .038 and oxygen consumption per kilogram 27.69 (7.52) vs 30.71 (7.52); P = .036 at peak exercise. The 2 independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (OR: .79 per 10 beats/minute; 95% CI: .65–.96; P = .019) and long-COVID memory impairment (OR: 3.76; 95% CI: 1.57–9.01; P = .003).
Conclusions
Long-COVID fatigue may be related to autonomic dysfunction, impaired cognition, and decreased mood. This may suggest a limbic-vagal pathophysiology.
Clinical Trials Registration
NCT04851561.
Long-COVID fatigue substantially correlates with depression and poorer sleep. Decreased peak exercise heart rate, which may reflect mild autonomic dysfunction, and long-COVID memory impairment, are independent risk factors for long-COVID fatigue.
Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation; however, cohesin ...mutant leukemias do not show genomic instability. We hypothesized that reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Biallelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation and revealed an absolute requirement for cohesin in hematopoietic stem cell (HSC) function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo, including competitive transplantation. Smc3 haploinsufficiency reduced coordinated transcriptional output, including reduced expression of transcription factors and other genes associated with lineage commitment. Smc3 haploinsufficiency cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5 signaling and altered nucleolar topology. These data establish a dose dependency for cohesin in regulating chromatin structure and HSC function.
•This study evaluated 2333 individuals at hospital-based COVID-19 recovery clinics.•Older adults are more likely to report long-COVID symptoms.•The most common long-COVID symptoms among older adults ...are fatigue and dyspnea.•Older age does not correlate with long-COVID fatigue or dyspnea.•Obesity is an independent risk factor for both long-COVID fatigue and dyspnea.
To describe long-COVID symptoms among older adults and to assess the risk factors for two common long-COVID symptoms: fatigue and dyspnea.
This is a multicenter, prospective cohort study conducted in Israel, Switzerland, Spain, and Italy. Individuals were included at least 30 days after their COVID-19 diagnosis. We compared long-COVID symptoms between elderly (aged >65 years) and younger individuals (aged 18-65 years) and conducted univariate and multivariable analyses for the predictors of long-COVID fatigue and dyspnea.
A total of 2333 individuals were evaluated at an average of 5 months (146 days 95% confidence interval 142-150) after COVID-19 onset. The mean age was 51 years, and 20.5% were aged >65 years. Older adults were more likely to be symptomatic, with the most common symptoms being fatigue (38%) and dyspnea (30%); they were more likely to complain of cough and arthralgia and have abnormal chest imaging and pulmonary function tests. Independent risk factors for long-COVID fatigue and dyspnea included female gender, obesity, and closer proximity to COVID-19 diagnosis; older age was not an independent predictor.
Older individuals with long-COVID have different persisting symptoms, with more pronounced pulmonary impairment. Women and individuals with obesity are at risk. Further research is warranted to investigate the natural history of long-COVID among the elderly population and to assess possible interventions aimed at promoting rehabilitation and well-being.
Prevention of mpox has become an important public health interest. We aimed to evaluate the safety and immunogenicity of the Modified Vaccinia Ankara (MVA) vaccine. We conducted a systematic review ...and meta-analysis of randomized-controlled trials (RCTs) comparing MVA versus no intervention, placebo, or another vaccine. Outcomes included safety and immunogenicity outcomes. We also performed a systematic review of RCTs evaluating various MVA regimens. Fifteen publications were included in the quantitative meta-analysis. All but one (ACAM2000) compared MVA with placebo. We found that cardiovascular adverse events following two MVA doses were significantly more common compared to placebo (relative risk RR 4.07, 95% confidence interval CI 1.10–15.10), though serious adverse events (SAEs) were not significantly different. Following a single MVA dose, no difference was demonstrated in any adverse event outcomes. Seroconversion rates were significantly higher compared with placebo after a single or two doses. None of the RCTs evaluated clinical effectiveness in preventing mpox. This meta-analysis provides reassuring results concerning the immunogenicity and safety of MVA. Further studies are needed to confirm the immunogenicity of a single dose and its clinical effectiveness. A single vaccine dose may be considered according to vaccine availability, with preference for two doses.
Long COVID has become a burden on healthcare systems worldwide. Research into the etiology and risk factors has been impeded by observing all diverse manifestations as part of a single entity. We ...aimed to determine patterns of symptoms in convalescing COVID-19 patients.
Symptomatic patients were recruited from four countries. Data were collected regarding demographics, comorbidities, acute disease and persistent symptoms. Factor analysis was performed to elucidate symptom patterns. Associations of the patterns with patients' characteristics, features of acute disease and effect on daily life were sought.
We included 1027 symptomatic post-COVID individuals in the analysis. The majority of participants were graded as having a non-severe acute COVID-19 (N = 763, 74.3%). We identified six patterns of symptoms: cognitive, pain-syndrome, pulmonary, cardiac, anosmia-dysgeusia and headache. The cognitive pattern was the major symptoms pattern, explaining 26.2% of the variance; the other patterns each explained 6.5-9.5% of the variance. The cognitive pattern was higher in patients who were outpatients during the acute disease. The pain-syndrome pattern was associated with acute disease severity, higher in women and increased with age. The pulmonary pattern was associated with prior lung disease and severe acute disease. Only two of the patterns (cognitive and cardiac) were associated with failure to return to pre-COVID occupational and physical activity status.
Long COVID diverse symptoms can be grouped into six unique patterns. Using these patterns in future research may improve our understanding of pathophysiology and risk factors of persistent COVID, provide homogenous terminology for clinical research, and direct therapeutic interventions.
Background: Persistent symptoms affect a subset of coronavirus disease 2019 (COVID-19) survivors. Some of these may be cardiovascular (CV)-related. Objective: To assess the burden of objective CV ...morbidity among, and to explore the short-term course experienced by, COVID-19 patients with post-infectious symptomatology suspected as CV. Methods: This was a single-center, retrospective analysis of consecutive adult patients with new-onset symptoms believed to be CV following recovery from COVID-19, who had been assessed at a dedicated ‘Cardio’-COVID clinic between June 2020 and June 2021. All participants were followed for 1 year for symptomatic course and the occurrence of new CV diagnoses and major adverse cardiovascular events (MACE). Results: A total of 96 patients (median age 54 (IQR, 44–64) years, 52 (54%) females) were included in the final analysis. Initial visits occurred within a median of 142 days after the diagnosis of acute COVID. Nearly all (99%) patients experienced a symptomatic acute illness, which was graded as severe in 26 (27%) cases according to the National Institutes of Health (NIH) criteria. Long-COVID symptoms included mainly dyspnea and fatigue. While the initial work-up was mostly normal, 45% of the 11 cardiac magnetic resonance studies performed revealed pathologies. New CV diagnoses were made in nine (9%) patients and mainly included myocarditis that later resolved. An abnormal spirometry was the only variable associated with these. No MACE were recorded. Fifty-two (54%) participants felt that their symptoms improved. No association was found between CV morbidity and symptomatic course. Conclusions: In our experience, long-COVID symptoms of presumed CV origin signified actual CV disease in a minority of patients who, irrespective of the final diagnosis, faced a fair 1-year prognosis.
COVID-19 has impacted hundreds of millions of people globally, a relatively large proportion of whom continue to suffer from ongoing, sometime debilitating symptoms. This phenomenon, termed "long ...COVID," is difficult to diagnose and manage because of a paucity of objective findings and despite the abundance of descriptive data published so far. In this review, we aimed to describe the common manifestations of long COVID, diagnostic and management challenges, and address specific aspects in hematologic patients.
Paul Garner, a professor of epidemiology at Liverpool School of Tropical Medicine, UK, wrote on the 95th day after the onset of symptoms that “I am unable to be out of bed for more than three hours ...at a stretch, my arms and legs are permanently fizzing as if injected with Szechuan peppercorns, I have ringing in the ears, intermittent brain fog, palpitations, and dramatic mood swings.” 1 Other people also describe similar complaints.2,3 78 of 100 patients in an observational cohort study who had recovered from COVID-19 had abnormal findings on cardiovascular MRI (median of 71 days after diagnosis) and 36 of those reported dyspnoea and unusual fatigue.4 We are seeing patients in clinics dedicated to COVID-19 convalescents, and for some of these patients the return to their former health trajectory is slow and painful. To avoid the problems we have witnessed in the research of the acute phase of the disease, a clear definition of patient inclusion criteria, a common protocol, and uniform definitions of outcomes and ways to measure them are required.
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