Tag: long covid symptoms

Endothelial dysfunction is the key of long COVID-19 symptoms: The results of TUN-EndCOV study

Abstract:

Background: The COVID-19 disease is a multisystem disease due to in part to the vascular endothelium injury. Lasting effects and long-term sequalae could persist after the infection and may be due to persistent endothelial dysfunction.

Purpose: Our study focused on the study of endothelial function measurement by digital thermal monitoring (DTM) of endothelial quality index with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long COVID-19 symptoms are due to endothelial dysfunction.

Methods: This is a prospective multicenter longitudinal observational cohort study. Endothelial function was evaluated with “E4-Diagnose” Polymath Tunisia based on the Endothelium Quality Index (EQI). A complete echocardiographic evaluation analysis was performed. Primary outcomes were defined as the occurrence of long COVID-19 symptoms in patients with endothelial dysfunction measured by EQI.

Results: A total of 798 patients were included in this study. Patients were included at an average time of 68.93 ± 43.1 days. The mean EQI was 2.02 ± 0.99 [0–5]. A total of 397 (49.7%) patients had poor or very poor EQI and 211 (26.4%) patients had very poor EQI. The median age was 49.94 ± 14.2 (18–80) years. A total of 618 patients (77.4%) had long COVID-19 symptoms. Patients with long COVID-19 symptoms had a reduced EQI (1.99 ± 0.97 vs. 2.09 ± 1.05, P = 0.24). Among long COVID-19 symptoms, fatigue was the most common symptom reported in 42.2%. Fatigue and chest pain were significantly associated to the endothelial dysfunction (P = 0.04 and 0.001 respectively). Patients with chest pain had significantly lower EQI (1.74 ± 1.0 vs. 2.09 ± 0.9, P ≤ 10−3) and LVGLS (−16.35 ± 3.0 vs. −17.16 ± 2.5, P = 0.04).

Conclusion: Long COVID-19 symptoms specifically chest pain and fatigue are due to persistent poor endothelial quality index. These findings allow a better care of patients with long COVID-19 symptoms.

Source: S. Charfeddine, H. Ibnhadjamor, S. Torjmen, S. Kraiem, R. Hammami, A. Bahloul, N. Kallel, N. Moussa, I. Touil, S. Milouchi, J. Elghoul, Z. Meddeb, Y. Thabet, J. Jdidi, K. Bouslema, S. Abdesselem, L. Abid. Endothelial dysfunction is the key of long COVID-19 symptoms: The results of TUN-EndCOV study. Archives of Cardiovascular Diseases Supplements, Volume 14, Issue 1, 2022, Page 126, ISSN 1878-6480, https://doi.org/10.1016/j.acvdsp.2021.10.004. (https://www.sciencedirect.com/science/article/pii/S187864802100642X)

Multisystem Involvement in Post-acute Sequelae of COVID-19 (PASC)

Abstract:

Objective: To describe cerebrovascular, neuropathic and autonomic features of post-acute sequelae of COVID-19 (PASC).

Methods: This retrospective study evaluated consecutive patients with chronic fatigue, brain fog and orthostatic intolerance consistent with PASC. Controls included postural tachycardia syndrome patients (POTS) and healthy participants. Analyzed data included surveys and autonomic (Valsalva maneuver, deep breathing, sudomotor and tilt tests), cerebrovascular (cerebral blood flow velocity (CBFv) monitoring in middle cerebral artery), respiratory (capnography monitoring) and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/autoimmune markers.

Results: Nine PASC patients were evaluated 0.7±0.3 years after a mild COVID-19 infection, treated as home observations. Autonomic, pain, brain fog, fatigue and dyspnea surveys were abnormal in PASC and POTS (n=10), compared to controls (n=15). Tilt table test reproduced the majority of PASC symptoms. Orthostatic CBFv declined in PASC (-20.0±13.4%) and POTS (-20.3±15.1%), compared to controls (-3.0±7.5%,p=0.001) and was independent of end-tidal carbon dioxide in PASC, but caused by hyperventilation in POTS. Reduced orthostatic CBFv in PASC included both subjects without (n=6) and with (n=3) orthostatic tachycardia. Dysautonomia was frequent (100% in both PASC and POTS) but was milder in PASC (p=0.013). PASC and POTS cohorts diverged in frequency of small fiber neuropathy (89% vs. 60%) but not in inflammatory markers (67% vs. 70%). Supine and orthostatic hypocapnia was observed in PASC.

Interpretation: PASC following mild COVID-19 infection is associated with multisystem involvement including: 1) cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction; 2) small fiber neuropathy and related dysautonomia; 3) respiratory dysregulation; 4) chronic inflammation.

Source: Novak P, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM. Multisystem Involvement in Post-acute Sequelae of COVID-19 (PASC). Ann Neurol. 2021 Dec 24. doi: 10.1002/ana.26286. Epub ahead of print. PMID: 34952975. https://pubmed.ncbi.nlm.nih.gov/34952975/

Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19

Abstract:

The incidence of infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for coronavirus disease 2019 (COVID-19), has dramatically escalated following the initial outbreak in China in late 2019, resulting in a global pandemic with millions of deaths. Although the majority of infected patients survive, and the rapid advent and deployment of vaccines have afforded increased immunity against SARS-CoV-2, long term sequelae of SARS-CoV-2 infection have become increasingly recognized. These include, but are not limited to, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurological dysfunction that may lead to psychological and neurocognitive impairment. A major component of cognitive dysfunction is operationally categorized as “brain fog” which comprises difficulty with concentration, forgetfulness, confusion, depression, and fatigue.

Multiple parameters associated with long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinical studies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations of COVID-19 are by nature complex, but broad based working models have focused on mitochondrial dysregulation leading to systemic reductions of metabolic activity and cellular bioenergetics within CNS structures. Multiple factors underlying the expression of brain fog may facilitate future pathogenic insults leading to repetitive cycles of viral and bacterial propagation. Interestingly, diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observed in other historical pandemics, thereby providing a broad and integrative perspective on potential common mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health status may be reciprocally linked to compromised immune processes and enhanced susceptibility to infection by diverse pathogens.

By extrapolation, we contend that COVID-19 may potentiate the severity of neurological/neurocognitive deficits in patients afflicted by well-studied neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Accordingly, the prevention, diagnosis, and management of sustained neuropsychiatric manifestations of COVID-19 are pivotal health care directives and provide a compelling rationale for careful monitoring of infected patients, as early mitigation efforts may reduce short- and long-term complications.

Source: Stefano GB, Büttiker P, Weissenberger S, Ptacek R, Wang F, Esch T, Bilfinger TV, Kream RM. Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19. Curr Neuropharmacol. 2021 Dec 23. doi: 10.2174/1570159X20666211223130228. Epub ahead of print. PMID: 34951387. https://pubmed.ncbi.nlm.nih.gov/34951387/

Physical, cognitive and mental health impacts of COVID-19 following hospitalisation – a multi-centre prospective cohort study

Abstract:

Background The impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood.

Methods PHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function.

Findings We report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity.

Interpretation We identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services.

Source: Sigfrid, Louise, et al. “Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.” medRxiv (2021).  https://www.medrxiv.org/content/10.1101/2021.03.22.21254057v1.full-text (Full text)

Long covid in adults discharged from UK hospitals after covid-19: a prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Abstract:

Background: This study sought to establish the long-term effects of Covid-19 following hospitalisation.

Methods: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L).

Findings: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age.

Interpretation: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.

Source: Sigfrid L, Drake TM, Pauley E, Jesudason EC, Olliaro P, Lim WS, Gillesen A, Berry C, Lowe DJ, McPeake J, Lone N, Munblit D, Cevik M, Casey A, Bannister P, Russell CD, Goodwin L, Ho A, Turtle L, O’Hara ME, Hastie C, Donohue C, Spencer RG, Donegan C, Gummery A, Harrison J, Hardwick HE, Hastie CE, Carson G, Merson L, Baillie JK, Openshaw P, Harrison EM, Docherty AB, Semple MG, Scott JT; ISARIC4C investigators. Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol. Lancet Reg Health Eur. 2021 Sep;8:100186. doi: 10.1016/j.lanepe.2021.100186. Epub 2021 Aug 6. PMID: 34386785; PMCID: PMC8343377. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343377/ (Full text)

Covid-19: Middle aged women face greater risk of debilitating long term symptoms

Middle aged women have a higher risk of experiencing a range of debilitating ongoing symptoms, such as fatigue, breathlessness, muscle pain, anxiety, depression, and “brain fog” after hospital treatment for covid-19, suggest the findings of two unpublished studies available as preprints.

Seven in 10 patients admitted to hospital with covid-19 reported “long covid” symptoms an average of five months after discharge in the larger PHOSP-COVID study, and symptoms were more prevalent in women aged 40-60.1 White ethnicity, two or more comorbidities at admission, and receiving invasive ventilation while in hospital increased the risk, but severity of acute covid-19 disease did not seem to affect the likelihood of experiencing long covid symptoms.

Only 29% of the 1077 patients studied felt fully recovered when followed up, on average five months after discharge. Over a quarter had clinically significant symptoms of anxiety and depression, 12% had symptoms of post-traumatic stress disorder, 17% had at least mild cognitive impairment, 46% had lower physical performance than age and sex matched controls, and 20% had a new disability.

Before hospital admission 68% of patients had worked full time, but 18% of these had not returned to work and 19% had had to change their way of working because of longlasting effects.

The researchers grouped patients into four clusters according to the severity of their physical and mental symptoms post-covid: very severe (17% of patients), severe (21%), moderate with cognitive impairment (17%), and mild (46%).

Rachael Evans, National Institute for Health Research clinical scientist at the University of Leicester and a study author, said, “The symptoms are very real, but they don’t have a straightforward relationship with heart and lung damage, or certainly heart and lung damage can’t explain all the symptoms.”

Immune response

A smaller second study, from the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC), found that women under 50 were five times less likely to report feeling recovered, twice as likely to report worse fatigue, seven times more likely to become more breathless, and more likely to have greater disability than men of the same age who had been admitted to hospital with covid-19.2 Disability usually affected memory, mobility, communication, vision, or hearing. More than half of the 327 patients assessed in this study did not feel fully recovered when followed up on average seven months later, and persistent symptoms were reported by 93.3%, with fatigue and breathlessness the most common.

Chris Brightling, professor of respiratory medicine at the University of Leicester and a PHOSP-COVID study researcher, speculated that sex based differences in the immune response may be responsible for the higher prevalence of long covid symptoms in women, noting that autoimmune diseases were more prevalent in women than in men at age 40-60.

“Maybe there’s a difference in the immune response acutely, such that men are more likely to have a more severe condition at the time of the infection,” he told a press conference at the Science Media Centre on 24 March. “It may be that the immune response is different in women, so you then have a continued inflammatory reaction that then leads to a higher likelihood of having long covid.”

Higher levels of C reactive protein, a marker of systemic inflammation, were seen in patients in the most severe long covid symptoms. Brightling said that a number of immune and chronic inflammatory conditions can also cause elevated C reactive protein.

About 450 000 people have been admitted to hospital with covid-19 in the UK, so a “very large” proportion of these would potentially be affected by long covid, he said, adding, “Clearly there’s an even larger number of people that have had covid in the community, and a portion of those will also have long covid.”

Source: Torjesen I. Covid-19: Middle aged women face greater risk of debilitating long term symptoms BMJ 2021; 372 :n829 doi:10.1136/bmj.n829 https://www.bmj.com/content/372/bmj.n829 (Full text)

Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest

People admitted to hospital with covid-19 who reported “long covid” symptoms five months after discharge had made only limited improvement after a full year, preliminary data from the PHOSP-COVID study show.

Researchers said that their results, released as a preprint on 16 December,1 showed that patients who experienced the most severe symptoms also had raised levels of substances associated with whole body inflammation and tissue damage and repair, suggesting autoimmune involvement.

The study, led by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, is following up 2230 adults admitted to hospital with covid-19. At five months after discharge only 2.5 in 10 people felt fully recovered.2 This was largely unchanged after 12 months, at less than 3 in 10 patients, in the 807 people assessed so far.

Chris Brightling, professor of respiratory medicine at the University of Leicester and chief investigator for the study, said, “People who were hospitalised and went on to develop long covid are not getting substantially better a year after they were discharged from hospital.

“Many patients in our study had not fully recovered at five months, and most of these reported little positive change in their health condition at one year.”

Rachael Evans, associate professor at the University of Leicester and respiratory consultant at Leicester’s Hospitals, who is the paper’s lead author, said, “Healthcare professionals will need to proactively continue assessing their patients for some time to come in order to identify their ongoing healthcare needs and provide support.

“We urgently need healthcare packages and medicines that target the potentially treatable traits of long covid to help people feel better and get back to their normal lives. Without these, long covid has the potential to become highly prevalent as a new long term condition.”

Ongoing inflammatory process

The most common long covid symptoms reported by patients were fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness, and patients said that their health related quality of life remained substantially worse one year after hospital discharge than before they had the SARS-CoV-2 infection.

A cluster analysis on the five month data revealed four distinct groups of patients based on the severity of symptoms they experienced: in 39% symptoms were considered mild, in 30% severe, in 20% very severe, and in 11% they were moderate or primarily affected cognition.

Blood samples taken at five months were analysed for around 300 substances linked to inflammation and immunity. These showed that patients in the “very severe” group had higher levels of substances associated with whole body inflammation, tissue damage, and tissue repair, while those reporting poor cognition appeared to have higher levels of substances linked to “brain fog,” suggesting possible neuro-inflammation.

Brightling said that the results suggested “an ongoing inflammatory process” and that other studies had indicated an increase in autoimmunity in some cases against specific organs such as heart or skeletal muscle. “We’re working very closely with immunologists to try to unpick that and see whether autoimmunity may be one of the key drivers [of long covid],” he said.

Source: Ingrid Torjesen. Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest. BMJ 2021;375:n3092. Published 15 December 2021. https://www.bmj.com/content/375/bmj.n3092 (Full text)

Cognitive sequelae of long COVID may not be permanent. A prospective study

Abstract:

Background and purpose: Cognitive decline is a recognized manifestation of long COVID, even among patients who experience mild disease. However, there is no evidence regarding the length of cognitive decline in these patients. This study aimed to assess whether COVID-19-related cognitive decline is a permanent deficit or if it improves over time.

Methods: Cognitive performance was evaluated by means of the Montreal Cognitive Assessment (MoCA) in COVID-19 survivors and noninfected individuals. All study participants had four cognitive evaluations, two of them before the pandemic and the other two, 6 and 18 months after the initial SARS-CoV-2 outbreak infection in the village. Linear mixed effects models for longitudinal data were fitted to assess differences in cognitive performance across COVID-19 survivors and noninfected individuals.

Results: The study included 78 participants, 50 with history of mild COVID-19 and 28 without. There was a significant-likely age-related-decline in MoCA scores between the two prepandemic tests (β = -1.53, 95% confidence interval [CI] = -2.14 to -0.92, p < 0.001), which did not differ across individuals who later developed COVID-19 when compared to noninfected individuals. Six months after infection, only COVID-19 survivors had a significant decline in MoCA scores (β = -1.37, 95% CI = -2.14 to -0.61, p < 0.001), which reversed after 1 additional year of follow-up (β = 0.66, 95% CI = -0.11 to 1.42, p = 0.092). No differences were noticed among noninfected individuals when both postpandemic MoCA scores were compared.

Conclusions: Study results suggest that long COVID-related cognitive decline may spontaneously improve over time.

Source: Del Brutto OH, Rumbea DA, Recalde BY, Mera RM. Cognitive sequelae of long COVID may not be permanent: A prospective study. Eur J Neurol. 2021 Dec 16. doi: 10.1111/ene.15215. Epub ahead of print. PMID: 34918425. https://pubmed.ncbi.nlm.nih.gov/34918425/

Symptoms and management of long COVID: A scoping review

Abstract:

Aim: This scoping review aims to describe published work on the symptoms and management of long COVID conditions.

Background: Symptoms and management of COVID-19 have focused on the acute stage. However, long-term consequences have also been observed.

Methods: A scoping review was performed based on the framework suggested by Arksey and O’Malley. We conducted a literature search to retrieve articles published from May 2020 to March 2021 in CINHAL, Cochrane library, Embase, PubMed and Web of science, including backward and forward citation tracking from the included articles. Among the 1880 articles retrieved, 34 articles met our criteria for review: 21 were related to symptom presentation and 13 to the management of long COVID.

Results: Long COVID symptoms were described in 21 articles. Following COVID-19 treatment, hospitalised patients most frequently reported dyspnoea, followed by anosmia/ageusia, fatigue and cough, while non-hospitalised patients commonly reported cough, followed by fever and myalgia/arthralgia. Thirteen studies described management for long COVID: Focused on a multidisciplinary approach in seven articles, pulmonary rehabilitation in three articles, fatigue management in two articles and psychological therapy in one study.

Conclusion: People experience varied COVID-19 symptoms after treatment. However, guidelines on evidence-based, multidisciplinary management for long COVID conditions are limited in the literature. The COVID-19 pandemic may extend due to virus mutations; therefore, it is crucial to develop and disseminate evidence-based, multidisciplinary management guidelines.

Relevance to clinical practice: A rehabilitation care plan and community healthcare plans are necessary for COVID-19 patients before discharge. Remote programmes could facilitate the monitoring and screening of people with long COVID.

Source: Chiyoung Cha PhD, RN,Gumhee Baek Master Candidate, RN. Symptoms and management of long COVID: A scoping review. First published: 15 December 2021. https://doi.org/10.1111/jocn.16150

Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode

Summary:

AIM OF THE STUDY: Patients surviving COVID-19 have been described as being at risk of developing sequelae. We aimed to investigate and elicit persistent symptoms, emotional status and quality-of-life in patients discharged after an acute COVID-19 episode.

METHODS: Patient-reported outcome measures were collected during a telephone interview 30 days and 1 year after discharge. Patients’ general health status was evaluated using questions based on their symptoms, emotional status was assessed using the items 9 to 12 of the HeartQoL questionnaire and quality of life was assessed at 1 year through the EQ-5D-5L. In patients with a history of cardiovascular disease, all 14 items of the HeartQoL questionnaire were completed to derive the HeartQoL global score.

RESULTS: Among 687 patients who survived after being hospitalised for COVID-19 at the University Hospitals of Geneva between 26 February and 26 April 2020, 184 (27%) and 165 (24%), respectively, participated in the follow-up at 30 days and 1 year. Of these 184 participants, 62% were male, median age was 58 years and 21% had a past medical history of cardiovascular disease. At one month after discharge, 61% (113/184) of patients presented fatigue and 28% (52/184) dyspnoea. One year after discharge, the main complaints were persistent fatigue in 27% (45/165) of patients, neurological problems in 17% (28/165) and dyspnoea in 14% (23/165). Eight percent (14/184) of patients declared being significantly worried 1 month after discharge and 5% (9/184) feeling depressed. The number of patients reporting being significantly worried or depressed at 1 year was lower. Regarding the quality of life at 1 year, the median EQ-5D-5L visual analogue scale score was 80 (interquartile range 70–90).

CONCLUSIONS: Approximately half of patients reported some symptoms 1 year after discharge following an acute episode of COVID-19. The predominant symptom was persistent fatigue both at 1-month and at 1-year follow-up. Emotional status and quality of life appeared satisfactory.

ClinicalTrials.gov number: NCT04384029

Source: Elena Tessitorea, Sandra Handgraafa, Antoine Poncetb, Maëlle Achardac, Stefan Höferd, Sebastian Carballoe, Christophe Martie, Cédric Follonierac, François Girardinfg, François Macha, David Carballoa. Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode. Swiss Med Wkly. 2021;151:w30093. Publication Date: 13.12.2021. https://smw.ch/article/doi/smw.2021.w30093 (Full text)