Tag: long covid symptoms

Autonomic dysfunction in long-COVID syndrome: a neurophysiological and neurosonology study

Dear Sirs,

A significant proportion of patients infected from SARS-CoV-2 experience new, recurring, or ongoing symptoms usually 3 months after infection that may last for weeks or months and comprise the so-called Long-COVID Syndrome (LCS). Most frequent neurological symptoms include fatigue, memory/attention deficits, sleep disorders, myalgias and hyposmia []. The occurrence of LCS is not associated with the severity of foregoing acute COVID-19 nor have specific predisposing factors been identified so far. LCS shares common features with two other diseases, Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS): young women are predominantly affected, the etiology is unknown, although a previous viral infection is suspected, and both conditions have symptoms similar to those of LCS. Autonomic Nervous System (ANS) maladaptation has been proposed as a possible pathogenetic underlying mechanism. [, ]

Hence, a case–control study was conducted to investigate if ANS dysfunction may contribute to LCS. Consecutive, adult patients, with history of laboratory-confirmed COVID-19 without hospitalization, presenting with persistent LCS symptoms for > 3 months from COVID-19 onset, including fatigue, cognitive impairment (brain fog), orthostatic dizziness, palpitations, breathlessness or gastrointestinal symptoms, were evaluated at a referral center in Athens, Greece (“Attikon” University Hospital) between September 2021 and December 2021. LCS patients with cardiovascular complications or diabetes were excluded. Controls included colleagues, nursing staff and volunteers without history of SARS-COV-2 infection, cardiovascular diseases, diabetes and ANS disorders. Evaluation of ANS function was performed by Sympathetic Skin Response (SSR) to investigate the Sympathetic Nervous System (SNS), and the cross-sectional area (CSA) of the Vagus Nerve (VN) was assessed by ultrasound to investigate the Parasympathetic Nervous System (PNS) []. A detailed description of the methods is available in the online-only supplement. The study was approved by the Institutional Research Bioethics. Informed consent was obtained by all participants. Statistical analysis was performed using the Statistical Package for Social Science (SPSS Inc., version 24.0 for Windows; IBM, Armonk, NY, USA). Descriptive statistics are given as the mean and standard deviation, frequency, and percentage. Statistical comparisons between different groups were performed using the chi-square test (or exact test) for binary outcomes, and Student’s t test or Mann–Whitney U test for continuous variables as appropriate.

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Source: Papadopoulou M, Bakola E, Papapostolou A, Stefanou MI, Gaga M, Zouvelou V, Michopoulos I, Tsivgoulis G. Autonomic dysfunction in long-COVID syndrome: a neurophysiological and neurosonology study. J Neurol. 2022 May 10:1–2. doi: 10.1007/s00415-022-11172-1. Epub ahead of print. PMID: 35536408; PMCID: PMC9086662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086662/ (Full text)

Exploring trajectory recovery curves of post-COVID cognitive symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study

Dear Sirs,

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, responsible of causing coronavirus disease 2019 (COVID-19), primary affects the respiratory system; however, neurological symptoms (e.g., ageusia, anosmia, headache) and also other severe complication are commonly experienced at the acute phase [, ]. Neurological symptoms presented at the acute COVID-19 phase such as headache [] or anosmia [] are likely present at a post-COVID phase; however, other neurological symptoms, e.g., cognitive disorders, are “de novo” developed in up to 22% of COVID-19 survivors []. A recent meta-analysis reported prevalence rates of 32%, 27% and 22% for post-COVID brain fog, memory loss, and attention/concentration problems the six months after respectively []. However, the presence of post-COVID cognitive symptoms are questioned by others [].

Interestingly, the recent definition of post-COVID includes cognitive dysfunction as one of the most common symptoms, after fatigue or dyspnoea []. The presence of post-COVID symptoms is overall associated with worse quality of life []. In fact, the presence of post-COVID cognitive symptoms represents a challenge for affected individuals since these symptoms affect daily life []. Although the presence of post-COVID cognitive symptoms is associated with nervous system changes [], it seems that these symptoms generally improve over time []. However, most studies investigating these symptoms have used cross-sectional designs. Therefore, understanding the longitudinal pattern of post-COVID cognitive symptoms may have significant implications in diagnosis, triaging, and management of post-COVID individuals.

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Source: Fernández-de-Las-Peñas C, Martín-Guerrero JD, Cancela-Cilleruelo I, Rodríguez-Jiménez J, Moro-López-Menchero P, Pellicer-Valero OJ. Exploring trajectory recovery curves of post-COVID cognitive symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study. J Neurol. 2022 May 10:1–5. doi: 10.1007/s00415-022-11176-x. Epub ahead of print. PMID: 35538169; PMCID: PMC9090121. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090121/ (Full text)

Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

Abstract:

Background: Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.

Methods: A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.

Results: Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47-169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1-3 months and p 0.01 at 6-9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1-3 months follow up, but not at 6-9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments.

Conclusion: Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.

Source: Buonsenso D, Munblit D, Pazukhina E, Ricchiuto A, Sinatti D, Zona M, De Matteis A, D’Ilario F, Gentili C, Lanni R, Rongai T, Del Balzo P, Fonte MT, Valente M, Zampino G, De Rose C, Sigfrid L, Valentini P; FIMP-Roma. Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol. Front Pediatr. 2022 Apr 21;10:834875. doi: 10.3389/fped.2022.834875. PMID: 35529336; PMCID: PMC9070551.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070551/ (Full text)

Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician

Abstract:

Purpose of review: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection.

Recent findings: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.

Source: Tobler DL, Pruzansky AJ, Naderi S, Ambrosy AP, Slade JJ. Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician. Curr Atheroscler Rep. 2022 May 4:1–8. doi: 10.1007/s11883-022-01032-8. Epub ahead of print. PMID: 35507278; PMCID: PMC9065238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065238/ (Full text)

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series

Abstract:

in English, Portuguese

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified.

(Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).

Source: Baldi BG, Fabro AT, Franco AC, Machado MHC, Prudente RA, Franco ET, Marrone SR, Vale SAD, Cezare TJ, Moraes MPT, Ferreira EVM, Albuquerque ALP, Sawamura MVY, Tanni SE. Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series. J Bras Pneumol. 2022 Apr 29;48(3):e20210438. doi: 10.36416/1806-3756/e20210438. PMID: 35508067; PMCID: PMC9064656. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9064656/  (Full text)

Long COVID and neuropsychiatric manifestations (Review)

Abstract:

There is accumulating evidence in the literature indicating that a number of patients with coronavirus disease 2019 (COVID-19) may experience a range of neuropsychiatric symptoms, persisting or even presenting following the resolution of acute COVID-19. Among the neuropsychiatric manifestations more frequently associated with ‘long COVID’ are depression, anxiety, post-traumatic stress disorder, sleep disturbances, fatigue and cognitive deficits, that can potentially be debilitating and negatively affect patients’ wellbeing, albeit in the majority of cases symptoms tend to improve over time.

Despite variations in results obtained from studies using different methodological approaches to define ‘long COVID’ syndrome, the most widely accepted factors associated with a higher risk of developing neuropsychiatric manifestations include the severity of foregoing COVID-19, the female sex, the presence of comorbidities, a history of mental health disease and an elevation in the levels of inflammatory markers, albeit further research is required to establish causal associations. To date, the pathophysiological mechanisms implicated in neuropsychiatric manifestations of ‘long COVID’ remain only partially elucidated, while the role of the indirect effects of the COVID-19 pandemic, such as social isolation and uncertainty concerning social, financial and health recovery post-COVID, have also been highlighted.

Given the alarming effects of ‘long-COVID’, interdisciplinary cooperation for the early identification of patients who are at a high risk of persistent neuropsychiatric presentations, beyond COVID-19 recovery, is crucial to ensure that appropriate integrated physical and mental health support is provided, with the aim of mitigating the risks of long-term disability at a societal and individual level.

Source: Efstathiou V, Stefanou MI, Demetriou M, Siafakas N, Makris M, Tsivgoulis G, Zoumpourlis V, Kympouropoulos SP, Tsoporis JN, Spandidos DA, Smyrnis N, Rizos E. Long COVID and neuropsychiatric manifestations (Review). Exp Ther Med. 2022 May;23(5):363. doi: 10.3892/etm.2022.11290. Epub 2022 Apr 1. PMID: 35493431; PMCID: PMC9019760. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019760/ (Full text)

The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome

Abstract:

Introduction: This study aimed to evaluate chronic pain and fatigue in patients 12 months after hospitalization for Covid-19.

Methods: We studied the COVID-19 patients discharged from Hospital, March 10 and April 20, 2020.

Results: A total of 157 patients were included in this study. Forty-three patients (27.4%) complained of chronic fatigue and muscle weakness in the last six months. The visual analog fatigue scale (VAFS) score of 3.84 ± 1.48 was obtained. Forty patients (25.5%) were suspected of Chronic Fatigue Syndrome (CFS).Twenty-four patients (15.3%) had severe chronic pain or exacerbation of previous chronic pain, most of which were reported in the lower back (70.8%) and lower extremities (66.7%). Pain intensity had a mean score of 2.33 ± 0.87 and was mainly described as “muscle cramps,” “persistent dull pain,” and “boring and numbing.” In women, chronic pain and fatigue, extended hospital stays, ICU admission, and depressed mood were common than in men.For these pain and fatigue, 37% used nonsteroidal anti-inflammatory drugs, and 16.3% used antidepressants. Only one person had applied for physiotherapy, and none of the patients had received psychotherapy.

Conclusion: Fatigue and chronic pain in patients recovering from COVID-19 are common complications, even after 12 months of illness.

Source: Janbazi L, Kazemian A, Mansouri K, Madani SP, Yousefi N, Vahedifard F, Raissi G. The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome. Am J Phys Med Rehabil. 2022 Apr 13. doi: 10.1097/PHM.0000000000002030. Epub ahead of print. PMID: 35473921.  https://pubmed.ncbi.nlm.nih.gov/35473921/

Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review

Abstract:

Introduction: This study aims to examine the worldwide prevalence of post COVID-19 condition, through a systematic review and meta-analysis.

Methods: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random effects framework with DerSimonian-Laird estimator, we meta-analyzed post COVID-19 condition prevalence at 28+ days from infection.

Results: 50 studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post COVID-19 condition was 0.43 (95% CI: 0.39,0.46). Hospitalized and non-hospitalized patients have estimates of 0.54 (95% CI: 0.44,0.63) and 0.34 (95% CI: 0.25,0.46), respectively. Regional prevalence estimates were Asia- 0.51 (95% CI: 0.37,0.65), Europe- 0.44 (95% CI: 0.32,0.56), and North America- 0.31 (95% CI: 0.21,0.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI: 0.26,0.49), 0.25 (95% CI: 0.15,0.38), 0.32 (95% CI: 0.14,0.57) and 0.49 (95% CI: 0.40,0.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI: 0.17,0.30), followed by memory problems (0.14 [95% CI: 0.10,0.19]).

Discussion: This study finds post COVID-19 condition prevalence is substantial; the health effects of COVID-19 appear to be prolonged and can exert stress on the healthcare system.

Source: Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review. J Infect Dis. 2022 Apr 16:jiac136. doi: 10.1093/infdis/jiac136. Epub ahead of print. PMID: 35429399. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac136/6569364?login=false (Full text available as PDF file)

The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study

Abstract:

The relationship between Long Covid (LC) symptoms and physical activity (PA) levels are unclear. In this cross-sectional study, we examined this association, and the advice that individuals with LC received on PA. Adults with LC were recruited via social media. The New Zealand physical activity questionnaire short form (NZPAQ-SF) was adapted to capture current and pre-COVID-19 PA levels and activities of daily living (ADLs).
Participants reported how PA affected their symptoms, and what PA recommendations they had received from healthcare professionals and other resources; 477 participants completed the survey. Mean age (SD) was 45.69 (10.02) years, 89.1% female, 92.7% white, and median LC duration was 383.5 days (IQR: 168.25,427). Participants were less active than pre-COVID-19 (26.88 ± 74.85 vs. 361.68 ± 396.29 min per week, p < 0.001) and required more assistance with ADLs in a 7-day period compared to pre-COVID-19 (2.23 ± 2.83 vs. 0.11 ± 0.74 days requiring assistance, p < 0.001). No differences were found between the number of days of assistance required with ADLs, or the amount of PA, and the different durations of LC illness (p > 0.05).
Participants reported the effect of PA on LC symptoms as: worsened (74.84%), improved (0.84%), mixed effect (20.96%), or no effect (28.72%). Participants received contradictory advice on whether to be physically active in LC. LC is associated with a reduction in PA and a loss of independence, with most participants reporting PA worsened LC symptoms. PA level reduction is independent of duration of LC. Research is needed to understand how to safely return to PA without worsening LC symptoms.
Source: Wright J, Astill SL, Sivan M. The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study. International Journal of Environmental Research and Public Health. 2022; 19(9):5093. https://doi.org/10.3390/ijerph19095093  https://www.mdpi.com/1660-4601/19/9/5093/htm (Full text)

Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study

Abstract:

Background: Fatigue is the most prevalent and debilitating long COVID 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: 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: Total of 141 individuals were included. Mean age was 47 (SD 13) years; 115 (82%) were recovering from mild 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 significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness and long COVID symptoms, and of physical limitation in daily activities. Individuals with fatigue 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=0.038] and oxygen consumption per Kg [27.69 (7.52) vs 30.71 (7.52), p=0.036] at peak exercise. The two independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (odds ratio [OR] 0.79 per 10 beats/minute, 95% confidence interval [CI] 0.65-0.96, p=0.019); and long COVID memory impairment (OR 3.76, 95% CI 1.57-9.01, p=0.003).

Conclusions: Long COVID fatigue may be related to autonomic dysfunction, impaired cognition and decreased mood. This may suggest a limbic-vagal pathophysiology. Clinical Trial registration: NCT04851561.

Source: Margalit I, Yelin D, Sagi M, Rahat MM, Sheena L, Mizrahi N, Gordin Y, Agmon H, Epstein NK, Atamna A, Tishler O, Daitch V, Babich T, Abecasis D, Yarom Y, Kazum S, Shitenberg D, Baltaxe E, Elkana O, Shapira-Lichter I, Leibovici L, Yahav D. Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study. Clin Infect Dis. 2022 Apr 11:ciac283. doi: 10.1093/cid/ciac283. Epub ahead of print. PMID: 35403679.  https://pubmed.ncbi.nlm.nih.gov/35403679/