Tag: long covid symptoms

A National Evaluation of Outcomes in Long COVID Services using Digital PROM Data from the ELAROS Platform

Summary:

Key findings of this service evaluation study:
• Patient characteristics: A sample of 5,318 patients from 14 participating NHS LC sites were analysed. The sample had a female:male ratio of 2.1:1. The average age was 48.4 yrs, with 87% (of those whose ethnicity was recorded) of white ethnicity and 9% of Black or Asian ethnicity.
• Comorbidities: This sample of patients had a low prevalence of co-morbidities (7%) with a clear onset of new LC symptoms after their COVID-19 infection supporting the onset of a new condition in this cohort of previously healthy individuals.
• Duration of LC: The average duration of LC in this sample was 384 days (>12 months) at first assessment in an LC site, with symptoms still ongoing at presentation, with more than 90% of the sample being non-hospitalised patients.
• Digital platform: A total of 17,471 PROMs (C19-YRS and EQ-5D-5L) were completed by this sample of patients with at least 1,532 participants completing multiple assessments on the same PROM on the digital PROM platform. The completion of PROMs around the 3-month mark was low for both measures (11.7% for C19-YRS and 14.6% for EQ-5D-5L). The ones who completed PROMs both around the 3-month mark and the 6-month mark were 4.3% for C19-YRS and 5% for EQ-5D-5L. This limits the generalisability of the findings in this evaluation to all the LC population, but the findings remain valid for this cohort of individuals.
• New-onset disability: 3,395 patients who completed at least one C19-YRS questionnaire at first assessment showed significant new-onset symptom burden, functional disability, and deterioration of overall health since the COVID-19 infection.
• Comparison between LC and other chronic conditions: The cross-sectional EQ-5D-5L Index value of 3,438 patients suggests the burden and disability in LC are worse than that reported in the literature for Diabetes Mellitus, COPD, Heart Failure, and Multiple Sclerosis.
• 3-month follow-up: Among those who completed an initial C19-YRS assessment and another at 3 months, there was a statistically significant improvement in symptom burden, functional disability and overall health. Patients at 3 months however still had significant LC symptom
burden and disability compared to their pre-COVID-19 health status, i.e., their condition had improved, but they were far off from a complete recovery. Among those who completed EQ-5D- National Evaluation of Long COVID Service Outcomes using ELAROS Data (09 Oct 23) Page 3 of 31
5L, at first assessment and at 3 months, their EQ-5D-5L Index score did not show any statistically significant improvement, but the EQ-5D-5L VAS showed a statistically significant improvement.
• 6-month follow-up: Among those who completed measures at the first assessment, 3 months, and 6 months, C19-YRS and EQ-5D-5L VAS showed statistically significant improvement whereas EQ-5D-5L Index Value showed statistically significant deterioration. Patients at 6 months still had
significant LC symptom burden and disability compared to their pre-COVID-19 health status, i.e., their condition had improved but had not fully recovered. The follow-up changes in scores support the efficacy of interventions provided by LC services and suggest that continued specialist input is needed to manage these patients with persistent symptoms.
• C19-YRS (condition-specific measure) vs EQ-5D-5L (generic measure): The 3-month month follow-up changes in scores and responsiveness of PROMs highlight that C19-YRS is a more sensitive measure than EQ-5D-5L in this cohort of individuals with LC. This is in keeping with the literature recommending the use of condition-specific measures in addition to EQ-5D-5L.
• Vocational problems: 62% of this sample had their work role affected with them having to either be on sick leave, reduce hours, change roles, or quit roles. Only 21% were able to maintain their previous roles held prior to their COVID-19 infection. This is suggestive of considerable productivity loss and financial implications to the country.
• Fluctuating condition: In patients who completed multiple assessments, it was evident that LC is a fluctuant condition with no necessary linear trend of improvement or deterioration between the domains of symptom burden, functional disability, and overall health. This highlights the need to understand the triggers for the condition and invest in self-management and ongoing support from community healthcare services.
• Long-Term Condition: In most patients in this sample, LC has evidently become a Long-Term Condition (LTC) with fluctuations in their condition causing disability and significant deterioration of their overall health status seen even after 18 months of LC with no complete resolution or full recovery. There needs to be a national investment in managing this new LTC along with other LTCs.

Source: Dr Manoj Sivan, et al.  A National Evaluation of Outcomes in Long COVID Services using Digital PROM Data from the ELAROS Platform. National Evaluation of Long COVID Service Outcomes using ELAROS Data (09 Oct 23) https://locomotion.leeds.ac.uk/wp-content/uploads/sites/74/2023/10/National-Evaluation-of-LC-Service-Outcomes-using-ELAROS-Data-09-10-23.pdf (Full text)

A prospective randomized, double-blind placebo-controlled study to evaluate the effectiveness of neuroprotective therapy using functional brain MRI in patients with post-covid chronic fatigue syndrome

Abstract:

Background and purpose: to assess executive network using resting-state fMRI and patterns of brain activation using task fMRI with a cognitive paradigm, against the background of taking the drug in comparison with placebo in patients with post-COVID asthenic syndrome.

Methods: The study employed a prospective, randomized, double-blind, placebo-controlled trial approach to assess the efficacy of utilizing functional MRI of the brain as a neuroprotective therapy for treating patients with chronic fatigue syndrome following COVID-19. The study included 30 patients matched by sex and age with post-COVID asthenic syndrome. All patients were examined with MFI-20, MoCA, FAS-10 scales, MRI using a Siemens MAGNETOM Prisma 3 T scanner before and after a course of therapy with coordination complex with succinate acid anion (CCSA) or placebo (15 patients each) using resting state fMRI and with cognitive paradigm.

Results: The changes obtained as a result of the treatment of post-Covid asthenic syndrome demonstrated clinical superiority in the reduction of asthenic symptoms for the group of patients treated with CCSA (MFI-20 scores: -20·0 points in the CCSA group compared to -12 points in the placebo group, p = 0·043). The data obtained also correlate with the analysis of task fMRI and resting state fMRI may indicate an increase in the functional cognitive status after a course of therapy with CCSA. Clinically, this correlates with a statistically significant improvement in the MoCA score (2 points in the CCSA group compared to 1 point in the placebo group, p < 0·05).

Conclusions: The study demonstrates the potential effectiveness of CCSA therapy in relation to a wide range of symptoms (chronic fatigue syndrome/ asthenic syndrome and cognitive impairment) in patients with post-COVID syndrome. The first time demonstrated the effectiveness of neuroprotective therapy after post-COVID asthenic syndrome with the use of high-tech neuroimaging techniques.

Source: Tanashyan M, Morozova S, Raskurazhev A, Kuznetsova P. A prospective randomized, double-blind placebo-controlled study to evaluate the effectiveness of neuroprotective therapy using functional brain MRI in patients with post-covid chronic fatigue syndrome. Biomed Pharmacother. 2023 Oct 18;168:115723. doi: 10.1016/j.biopha.2023.115723. Epub ahead of print. PMID: 37862966. https://www.sciencedirect.com/science/article/pii/S0753332223015214 (Full study)

Insomnia and sleep characteristics in post COVID-19 fatigue: A cross-sectional case-controlled study

Abstract:

Objective: Following COVID-19 many patients report persistent fatigue and insomnia. Given the overlapping features, insomnia can be underdiagnosed in post-COVID-19 fatigue patients. This study aimed to determine insomnia severity, prevalence of clinical insomnia and sleep characteristics of post-COVID-19 fatigue patients. Data of post-COVID-19 fatigue patients were compared with those of patients with chronic fatigue syndrome (ME/CFS), a condition resembling post-COVID-19 fatigue.

Methods: In this cross-sectional case-controlled study, insomnia severity, assessed with the Insomnia Severity Index (ISI), and prevalence of clinical insomnia (ISI score ≥ 10), were determined in patients with post-COVID-19 fatigue (n = 114) and compared with ME/CFS (n = 59) using ANCOVA and logistic regression, respectively. Linear regression analyses were used to evaluate whether mood, concentration problems, pain, fatigue (assessed with questionnaires) and diagnosis were associated with insomnia. Sleep characteristics were determined with a sleep diary and accelerometer in post-COVID-19 fatigue and compared with ME/CFS using ANCOVA.

Results: In patients with post-COVID-19 fatigue mean (SD) insomnia severity was 11.46 (5.7) and 64% reported clinical insomnia. Insomnia severity was significantly associated with depressive symptoms (ß = 0.49, p = 0.006) and age (ß = 0.08, p = 0.04). The mean (SD) subjective sleep duration was 7.4 (1.0) hours with a sleep efficiency of 82 (11)%. Several subjective sleep characteristics of the post-COVID-19 fatigue patients differed from ME/CFS patients; only sleep duration, being significantly shorter in post-COVID-19 fatigue patients (p = 0.003), seemed clinically relevant (d = 0.58).

Conclusion: Insomnia severity and prevalence of clinical insomnia are high in patients with post-COVID-19 fatigue. Insomnia should be assessed and if present treated with insomnia focused therapy.

Source: Nynke L. Rauwerda, Tanja A. Kuut, Annemarie M.J. Braamse, Irene Csorba, Pythia Nieuwkerk, Annemieke van Straten, Hans Knoop. Insomnia and sleep characteristics in post COVID-19 fatigue: A cross-sectional case-controlled study. Journal of Psychosomatic Research, 2023, 111522.ISSN 0022-3999, https://doi.org/10.1016/j.jpsychores.2023.111522.https://www.sciencedirect.com/science/article/pii/S0022399923003793

Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms

Approximately one third of non-hospitalized coronavirus disease of 2019 (COVID-19) patients report chronic symptoms after recovering from the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some of the most persistent and common complaints of this post-acute COVID-19 syndrome (PACS) are cognitive in nature, described subjectively as “brain fog” and also objectively measured as deficits in executive function, working memory, attention, and processing speed. The mechanisms of these chronic cognitive sequelae are currently not understood.

SARS-CoV-2 inflicts damage to cerebral blood vessels and the intestinal wall by binding to angiotensin-converting enzyme 2 (ACE2) receptors and also by evoking production of high levels of systemic cytokines, compromising the brain’s neurovascular unit, degrading the intestinal barrier, and potentially increasing the permeability of both to harmful substances. Such substances are hypothesized to be produced in the gut by pathogenic microbiota that, given the profound effects COVID-19 has on the gastrointestinal system, may fourish as a result of intestinal post-COVID-19 dysbiosis. COVID-19 may therefore create a scenario in which neurotoxic and neuroinflammatory substances readily proliferate from the gut lumen and encounter a weakened neurovascular unit, gaining access to the brain and subsequently producing cognitive deficits.

Here, we review this proposed PACS pathogenesis along the gut-brain axis, while also identifying specific methodologies that are currently available to experimentally measure each individual component of the model.

Source: Plummer Allison M., Matos Yvette L., Lin Henry C., Ryman Sephira G., Birg Aleksandr, Quinn Davin K., Parada Alisha N., Vakhtin Andrei A. Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms. Frontiers in Neuroscience, Vol 17, 2023. DOI=10.3389/fnins.2023.1232480 ISSN=1662-453X  https://www.frontiersin.org/articles/10.3389/fnins.2023.1232480 (Full text)

Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a recent worldwide coronavirus disease-2019 (COVID-19) pandemic. SARS-CoV-2 primarily causes an acute respiratory infection but can progress into significant neurological complications in some. Moreover, patients with severe acute COVID-19 could develop debilitating long-term sequela.

Long-COVID is characterized by chronic symptoms that persist months after the initial infection. Common complaints are fatigue, myalgias, depression, anxiety, and “brain fog,” or cognitive and memory impairments. A recent study demonstrated that a mild COVID-19 respiratory infection could generate elevated proinflammatory cytokines and chemokines in the cerebral spinal fluid.

This commentary discusses findings from this study, demonstrating that even a mild respiratory SARS-CoV-2 infection can cause considerable neuroinflammation with microglial and macrophage reactivity. Such changes could also be gleaned by measuring chemokines and cytokines in the circulating blood. Moreover, neuroinflammation caused by mild SARS-CoV-2 infection can also impair hippocampal neurogenesis, deplete oligodendrocytes, and decrease myelinated axons.

All these changes likely contribute to cognitive deficits in long-COVID syndrome. Therefore, strategies capable of restraining neuroinflammation, maintaining better hippocampal neurogenesis, and preserving oligodendrocyte lineage differentiation and maturation may prevent or reduce the incidence of long-COVID after SARS-CoV-2 respiratory infection.

Source: Wei ZD, Liang K, Shetty AK. Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments. Aging Dis. 2023 Sep 24. doi: 10.14336/AD.2023.10918. Epub ahead of print. PMID: 37815903. https://www.aginganddisease.org/EN/10.14336/AD.2023.10918 (Full text)

How long is Long-COVID? Symptomatic improvement between 12 and 18 months in a prospective cohort study

Abstract:

Introduction COVID-19 infection can precede, in a proportion of patients, a prolonged syndrome including fatigue, exercise intolerance, mood and cognitive problems. This study aimed to describe the profile of fatigue-related, exercise-related, mood-related and cognitive-related outcomes in a COVID-19-exposed group compared with controls.

Methods 113 serving UK Armed Forces participants were followed up at 5, 12 (n=88) and 18 months (n=70) following COVID-19. At 18 months, 56 were in the COVID-19-exposed group with 14 matched controls. Exposed participants included hospitalised (n=25) and community (n=31) managed participants. 43 described at least one of the six most frequent symptoms at 5 months: fatigue, shortness of breath, chest pain, joint pain, exercise intolerance and anosmia. Participants completed a symptom checklist, patient-reported outcome measures (PROMs), the National Institute for Health cognitive battery and a 6-minute walk test (6MWT). PROMs included the Fatigue Assessment Scale (FAS), Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and Patient Checklist-5 (PCL-5) for post-traumatic stress.

Results At 5 and 12 months, exposed participants presented with higher PHQ-9, PCL-5 and FAS scores than controls (ES (effect size) ≥0.25, p≤0.04). By 12 months, GAD-7 was not significantly different to controls (ES <0.13, p=0.292). Remaining PROMs lost significant difference by 18 months (ES ≤0.11, p≥0.28). No significant differences in the cognitive scales were observed at any time point (F=1.96, p=0.167). At 5 and 12 months, exposed participants recorded significantly lower distances on the 6MWT (ηp2≥0.126, p<0.01). 6MWT distance lost significant difference by 18 months (ηp2<0.039, p>0.15).

Conclusions This prospective cohort-controlled study observed adverse outcomes in depression, post-traumatic stress, fatigue and submaximal exercise performance up to 12 months but improved by 18-month follow-up, in participants exposed to COVID-19 compared with a matched control group.

Source: Barker-Davies RM, O’Sullivan O, Holdsworth DA, et alHow long is Long-COVID? Symptomatic improvement between 12 and 18 months in a prospective cohort studyBMJ Mil Health Published Online First: 03 October 2023. doi: 10.1136/military-2023-002500 https://militaryhealth.bmj.com/content/early/2023/10/03/military-2023-002500.abstract (Full text available as PDF file)

Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection

Abstract:

It is still unclear why certain individuals after viral infections continue to have severe symptoms. We investigated if predicting myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) development after contracting COVID-19 is possible by analyzing symptoms from the first two weeks of COVID-19 infection.
Using participant responses to the 54-item DePaul Symptom Questionnaire, we built predictive models based on a random forest algorithm using the participants’ symptoms from the initial weeks of COVID-19 infection to predict if the participants would go on to meet the criteria for ME/CFS approximately 6 months later.
Early symptoms, particularly those assessing post-exertional malaise, did predict the development of ME/CFS, reaching an accuracy of 94.6%. We then investigated a minimal set of eight symptom features that could accurately predict ME/CFS. The feature reduced models reached an accuracy of 93.5%. Our findings indicated that several IOM diagnostic criteria for ME/CFS occurring during the initial weeks after COVID-19 infection predicted Long COVID and the diagnosis of ME/CFS after 6 months.
Source: Hua C, Schwabe J, Jason LA, Furst J, Raicu D. Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection. Psych. 2023; 5(4):1101-1108. https://doi.org/10.3390/psych5040073 https://www.mdpi.com/2624-8611/5/4/73

Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity

Abstract:

Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs).

Methods: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge.

Results: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts.

Conclusion: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.

Source: Berentschot Julia C., Drexhage Hemmo A., Aynekulu Mersha Daniel G., Wijkhuijs Annemarie J. M., GeurtsvanKessel Corine H., Koopmans Marion P. G., Voermans Jolanda J. C., Hendriks Rudi W., Nagtzaam Nicole M. A., de Bie Maaike, Heijenbrok-Kal Majanka H., Bek L. Martine, Ribbers Gerard M., van den Berg-Emons Rita J. G., Aerts Joachim G. J. V., Dik Willem A., Hellemons Merel E. Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity. Frontiers in Immunology, vol 14, 2023. DOI=10.3389/fimmu.2023.1254899 ISSN=1664-3224 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1254899/full (Full text)

 

Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study

Abstract:

Objective: To determine if patients that develop lingering neurologic symptoms of fatigue and “brain fog” after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology.

Design: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function.

Results: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion.

Conclusions: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19.

Source: Wright TJ, Pyles RB, Sheffield-Moore M, Deer RR, Randolph KM, McGovern KA, Danesi CP, Gilkison CR, Ward WW, Vargas JA, Armstrong PA, Lindsay SE, Zaidan MF, Seashore J, Wexler TL, Masel BE, Urban RJ. Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study. Mol Cell Endocrinol. 2023 Oct 8:112071. doi: 10.1016/j.mce.2023.112071. Epub ahead of print. PMID: 37816478. https://www.sciencedirect.com/science/article/abs/pii/S0303720723002228

Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study

Abstract:

As the emergency phase of the COVID-19 pandemic subsides, the long-term health problems caused by SARS-CoV-2 infection are becoming increasingly clear. So-called Long COVID, or post COVID-19 condition, is a debilitating illness that impacts functioning for months and even years after infection. Alongside physical symptoms, Long COVID has a particularly insidious effect on cognition and language. While many studies have documented non-linguistic cognitive impairments in people with Long COVID, what has not been documented to any significant extent is the presence and duration of language difficulties in Long COVID. This study addresses this lack of research by examining the cognitive-linguistic skills of 41 adults with Long COVID.

These adults were assessed at two time points using a test protocol of 12 language tasks. This paper describes the findings of the 6-month follow-up study. Results indicate that difficulties in immediate and delayed verbal recall persist long after the onset of COVID symptoms, even as improvements occur in verbal fluency and the informativeness of spoken discourse.

It is argued that these difficulties are a significant contributing factor in a lack of work return in these adults. Implications of these findings for the provision of speech-language pathology services to these adults and occupational health policies relating to Long COVID are discussed.

Source: Louise Cummings. Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study. Language and Health. Available online 2 October 2023. https://www.sciencedirect.com/science/article/pii/S2949903823000325 (Full text)