Tag: long covid symptoms

Long COVID Clinical Phenotypes Up to Six Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms

Abstract:

Background: The prevalence, incidence, and interrelationships of persistent symptoms after SARS-CoV-2 infection (Long COVID) vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present three months and six months after acute infection.

Methods: This was a multicenter, prospective study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to six-months post-diagnosis. Using LCA, we identified symptomatically homogenous groups among participants with COVID-19 (COVID-positive) and among others without COVID-19 (COVID-negative) at each time period for both general and fatigue-related symptoms.

Results: Among 5,963 baseline participants (4,504 COVID-positive and 1,459 COVID-negative), 4,056 had three-month and 2,856 had six-month data at the time of analysis. We identified four distinct phenotypes of post-COVID conditions at three- and six-months for both general and fatigue-related symptoms; minimal symptom groups represented 70% of participants at three and six months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste and smell, as well cognition problems. There was substantial class-switching over time; those in one symptom class at three months were equally likely to remain or enter a new phenotype at six months.

Conclusions: We identified distinct classes of post-COVID phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at three and six months follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that post-COVID conditions may have a more dynamic nature than previously recognized.

Source: Michael Gottlieb, MD and others, Long COVID Clinical Phenotypes Up to Six Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms, Open Forum Infectious Diseases, 2023;, ofad277, https://doi.org/10.1093/ofid/ofad277 (Full text available as PDF file)

Do Pre-existing Sleep Disorders Worsen Long COVID Fatigue and Brain Fog?

Abstract:

Introduction: Long COVID is common after COVID-19 infection and leads to functional limitations with most reporting substantial symptom burden from fatigue. Symptoms in sleep disorders are attributed to inflammatory dysregulation and may predispose to fatigue expression. We hypothesize prior diagnoses of sleep disorders are associated with severity of long COVID fatigue.
Methods: A retrospective EMR review was performed of 210 consecutive adult patients (9/2021 to 2/2022) referred at least 3 months after COVID-19 infection seen in a new community-based long COVID clinic. The intake process collected demographics, past medical history, functional questionnaires, and symptom checklists. Primary outcome was Fatigue Severity Scale (FSS) score. Sleep disorders were evaluated as a composite of self-reported insomnia, sleep disordered breathing, and restless legs syndrome as well as subset analyses of each disorder. Secondary outcome was physical functioning measured by ECOG performance scale. Linear analyses were used for FSS and ECOG analyses. Adjustors included age, sex, body mass index (BMI), and whether patient had COVID-19 hospitalization.
Results: Cohort was female (66.2%), aged 51.6±SD14.4 yrs, BMI 29.8 [IQR 26.2, 37.7]). Prior chronic insomnia was present in 9%, sleep disordered breathing in 23%, and RLS in 4%; the pooled history of sleep disorders was 30%. Fatigue was reported in 76% with mean FSS score of 5.44 [interquartile range, IQR: 4.11,6.44]; 48% reported brain fog. The interval between acute COVID infection and clinic evaluation was 10.4±5.34 months and had no association to FSS severity (r = 0.07, p = 0.30). Sleep disorders in aggregate, insomnia, and restless legs syndrome had no associations with fatigue or functional status. Sleep disordered breathing had an association to fatigue in unadjusted (β = 0.68, 95% confidence interval, [CI]:0.13,1.24), but not adjusted models (β = 0.53, 95%CI: -0.06,1.13). Sleep disorders both in aggregate and evaluated individually had no associations to brain fog.
Conclusion: A prior history of sleep disorders contributed little to post-COVID fatigue reported in those presenting to a community-based Long COVID clinic.

Source: Isabelle Carter and others, 0967 Do Pre-existing Sleep Disorders Worsen Long COVID Fatigue and Brain Fog?, Sleep, Volume 46, Issue Supplement_1, May 2023, Pages A426–A427, https://doi.org/10.1093/sleep/zsad077.0967 (Full text is available as PDF file)

Diagnostic value of 24-h ECG recording in Long COVID patients with postural orthostatic tachycardia syndrome

Abstract:

Background: Cardiovascular autonomic dysfunction (CVAD) is a major complication for a large proportion of Long COVID (LC) patients. The main phenotype of CVAD is postural orthostatic tachycardia syndrome (POTS), commonly observed as a sequalae of COVID infection, thus defining a subset of LC patients. POTS is a cardiovascular autonomic disorder characterized by an excessive heart rate (HR) increase and symptoms of orthostatic intolerance when assuming upright posture, occurring predominantly in young and middle-aged women. Since the start of COVID-19 pandemic it has been observed that up to 30% of patients with post-COVID-19 syndrome develop POTS with such symptoms as tachycardia, orthostatic intolerance, fatigue, and cognitive impairment. The heterogeneity of POTS symptoms makes the diagnosis and appropriate management of POTS more difficult and one of the first steps for clinicians is to develop and test relevant diagnostic methods for POTS.
Methods: Patients with persistent symptoms, 3 months after an acute SARS-CoV-2 infection were referred to the multi-disciplinary LC unit at a hospital in Sweden. Consecutive patients seen at this unit from 2021 to 2022 underwent a 24-h ECG recording. LC patients with POTS verified by active standing test and/or head-up tilt testing were prospectively enrolled in the study database and were compared with LC patients without POTS according to 3 specific analyses based on 24-h ECG recording : (1) cardiac autonomic activity expressed by heart rate variability, HRV (SDNN and RMSSD in ms) parameters, (2) awakening HR increase (HR mean 10 min before vs. 30 min after awakening) and (3) HR spikes (number/h if at least over than 30 bpm and at least during 30 s). Control group consisted of healthy subjects from 24-h ECG recordings database (HRV analysis) of a hospital in France. Data were expressed as mean (± standard deviation, SD) and frequencies (%).
Results: A total of 120 LC patients (mean age: 42.7 +/-9.97 y, 88% women) and 100 healthy subjects (mean age: 46.4 +/-10.2 y, 82% women) were included. LC with POTS (42%) was associated with (1) a decrease in most HRV parameters (mean SDNN: 86.8 +/-24.3 vs. 108.7 +/-24.1 ms, p=0.03), and the most reduced components were those related to the parasympathetic tone (mean RMSSD: 34,5 +/-20.4 vs. 45.6 +/-22.1 ms, p=0.04), (2) an abrupt and sustained increase in HR during the first 30 min after awakening (+30%, p<0.05) and (3) a higher number of HR spikes per h (1.4 +/-0.8 vs. 0.8 +/-0.7/h, p<0.001) compared with healthy subjects (HRV) and LC patients without POTS (awakenings and HR peaks) respectively.
Conclusion: A triple analysis of 24-h ECG recordings revealed presence of autonomic dysfunction in LC patients with POTS compared with those without POTS. This novel analysis may be introduced in the clinic for screening and therapy monitoring.

Source: D Hupin and others, Diagnostic value of 24-h ECG recording in Long COVID patients with postural orthostatic tachycardia syndrome, EP Europace, Volume 25, Issue Supplement_1, June 2023, euad122.626, https://doi.org/10.1093/europace/euad122.626 (Full text available as PDF file)

Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID

Abstract:

Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection increases autoantibody responses and whether vaccination can decrease autoimmunity in long COVID patients is unknown.

Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than COVID convalescent controls at 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination/booster does not decrease autoantibody titers.

In summary, we found that mild SARS-CoV-2 infection can induce persistent humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.

Source: Visvabharathy L, Zhu C, Orban ZS, Yarnoff K, Palacio N, Jimenez M, Lim PH, Penaloza-MacMaster P, Koralnik IJ. Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID. medRxiv [Preprint]. 2023 Apr 12:2023.04.07.23288243. doi: 10.1101/2023.04.07.23288243. PMID: 37090595; PMCID: PMC10120795. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120795/ (Full text)

Risks of digestive diseases in long COVID: Evidence from a large-scale cohort study

Abstract:

Objectives This study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on the long-term risk of digestive diseases in the general population.

Design Large-scale population-based cohort study based on a prospective cohort.

Setting UK Biobank cohort linked to multiple nationwide electronic health records databases.

Participants The cohort consisted of 112,311 individuals who survived the initial 30 days following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as two control groups: a contemporary group (n = 359,671) without any history of COVID-19, and a historical control group (n = 370,979) that predated the COVID-19 outbreak.

Main outcome measures Main outcomes were predefined digestive diseases. Hazard ratios and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting.

Results Compared with the contemporary control group, patients with previous COVID-19 infection had higher risks of digestive diseases, including functional gastrointestinal disorders (hazard ratios [HR] 1.95 (95% CI 1.62 to 2.35)); peptic ulcer disease (HR 1.27 (1.04 to 1.56)); gastroesophageal reflux disease (GERD) (HR 1.46 (1.34 to 1.58)); inflammatory bowel diseases (HR 1.40 (1.02 to 1.90)); gallbladder disease (HR 1.28 (1.13 to 1.46)); severe liver disease (HR 1.46 (1.12 to 1.90)); non-alcoholic liver disease (HR 1.33 (1.15 to 1.55)); and pancreatic disease (HR 1.43 (1.17 to 1.74)). The risks of GERD were stepwise increased with severity of the acute phase of COVID-19 infection. The results were consistent when using the historical cohort as the control group.

Conclusions Our study provides important insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing gastrointestinal disorders, with stepwise increased risk with the severity and persisting even after one year follow-up.

Source: Yuying Ma, Lijun Zhang, Rui Wei, Weiyu Dai, Ruijie Zeng, Dongling Luo, Rui Jiang, Huihuan Wu, Zewei Zhuo, Qi Yang, Jingwei Li, Felix W Leung, Chongyang Duan, Weihong Sha, Hao Chen. Risks of digestive diseases in long COVID: Evidence from a large-scale cohort study. medRxiv 2023.04.25.23289080; doi: https://doi.org/10.1101/2023.04.25.23289080 https://www.medrxiv.org/content/10.1101/2023.04.25.23289080v1.full-text (Full text)

Autonomic Nervous System Affection Due to Post Covid Syndrome

Identification of the Effects of Post Covid Syndrome on the Autonomic Nervous System With Heart Rate Variability

Post-Covid syndrome is defined as symptoms that develop in addition to respiratory symptoms in individuals who have had Covid-19 infection for more than 12 weeks. Symptoms such as fatigue, headache, cognitive impairment, dyspnea, heart palpitations, heat intolerance, digestive system disorders, sleep disorders, dermal problems, orthostatic intolerance come to the fore in individuals with post-Covid syndrome. It has been tried to be revealed in some studies that Covid-19 infection affects the autonomic nervous system (ANS) and the relationship between Post-Covid 19 syndrome and ANS dysfunction.
Heart rate variability (HRV) measurement method can be used to evaluate ANS activity. HRV is a non-invasive method and is a measure of the change in heart rate over a period of time. HRV is a scalar quantity that shows the time between two beats of the heart and defines the oscillations between the R-R intervals. In HRV measurements, time-dependent and frequency-dependent measurement results are obtained and from these measurements, time-dependent RMSSD (square root of the square of the difference of the R-R intervals) and frequency-dependent high-frequency (HF) and low frequency (LF) measurement components are used in relation to the sympathetic nervous system (CNS) and parasympathetic nervous system (PSS). HRV can be measured in short-term (5 minutes) in terms of measurement time.
The aim of this study is to clearly reveal the relationship between Post-Covid 19 syndrome and ANS dysfunction and to provide standardization related to HRV measurement method and sub-parameters.
Source: Ali Veysel Özden, M.D. Bahçeşehir University. Istanbul, Beşiktaş, Turkey, 34000. ICH GCP US Clinical Trials Registry, Clinical Trial NCT05502094 https://ichgcp.net/clinical-trials-registry/NCT05502094

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Summary:

Some patients remain unwell for months after “recovering” from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars.

In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.

Source: Anthony L. Komaroff and W. Ian Lipkin. ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front. Med., 02 June 2023. Sec. Infectious Diseases: Pathogenesis and Therapy. Volume 10 – 2023 | https://doi.org/10.3389/fmed.2023.1187163 (Full text)

Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study

Abstract:

Objective: To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection.

Design: Population based, longitudinal cohort.

Setting: General population of canton of Zurich, Switzerland.

Participants: 1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection.

Main outcome measures: Trajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection.

Results: 22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%)).

Conclusions: Up to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials.

Registrations: ISRCTN18181860

Source: Ballouz T, Menges D, Anagnostopoulos A, Domenghino A, Aschmann HE, Frei A, Fehr JS, Puhan MA. Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study. BMJ. 2023 May 31;381:e074425. doi: 10.1136/bmj-2022-074425. PMID: 37257891. https://www.bmj.com/content/381/bmj-2022-074425 (Full text)

Long-Term Headache and Cognitive Complaints Among Health Care Workers Who Acquired SARS-CoV-2

Abstract:

Introduction: Neurological manifestations are frequent after acquiring COVID-19 and may persist long-term as part of post-COVID-19 syndrome. Cognitive impairment, chronic fatigue, sleep disturbances, and headache complaints are the most reported neurological features. During the COVID-19 pandemic, health care workers were particularly vulnerable due to the high workload and levels of stress associated with this period, but acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may also contribute. The authors aimed to evaluate the neurological involvement of acquiring SARS-CoV-2 in a population of hospital health care workers and its impact on their personal and professional lives.

Methods: A sample of health care workers who did and did not acquire SARS-CoV-2 matched by age and sociodemographic variables was studied. Through an online questionnaire, data were collected regarding the symptoms in the acute phase of the disease (for those who acquired it) and for all in the last 6 months of the study period. Proportion of neurological complaints were compared between groups, adjusting for age, sex, and professional class (using a rate ratio (RR)).

Results: This study included 326 participants (174 cases and 152 controls). The mean age (standard deviation) was 39.7 (10.2) years, and the female:male ratio was 3:1. Headache and cognitive complaints were the most prevalent neurological complaints in the last 6 months of the study period. The health care workers who acquired SARS-CoV-2 were more likely to report headache and cognitive complaints than the control group (RR = 1.51, 95% confidence interval = 1.17-1.9 and RR = 2.02, 95% confidence interval = 1.53-2.65, respectively).

Conclusion: In a population of health care workers, those who acquired SARS-CoV-2 were more likely to have long-term cognitive complaints and persistent headaches.

Source: Marques AJ, Costa A, Almendra R, Maia L, Magalhães R, Cavaco S, Oliveira V, Correia M, Mendes M, Veiga A. Long-Term Headache and Cognitive Complaints Among Health Care Workers Who Acquired SARS-CoV-2. Perm J. 2023 May 29:1-8. doi: 10.7812/TPP/22.171. Epub ahead of print. PMID: 37246366. https://www.thepermanentejournal.org/doi/10.7812/TPP/22.171 (Full text)

The association between the number of symptoms and the severity of Post-COVID-Fatigue after SARS-CoV-2 infection treated in an outpatient setting

Abstract:

Background: Post-COVID-Fatigue (PCF) is one of the most reported symptoms following SARS-CoV-2 infection. Currently, research on persistent symptoms focuses mainly on severe infections, while outpatients are rarely included in observations.

Objective: To investigate whether the severity of PCF is related to the number of acute and persistent symptoms due to mild-to-moderate COVID-19 and to compare the most common symptoms during acute infection with the persistent symptoms in PCF patients.

Methods: A total of 425 participants were examined after COVID-19 treated as an outpatient (median 249 days [IQR: 135; 322] after acute disease) at the site of University Hospital Augsburg, Germany. The Fatigue Assessment Scale (FAS) was used to quantify the severity of PCF. The number of symptoms (maximum 41) during acute infection and persistent symptoms (during the last 14 days before examination) were added up to sum scores. Multivariable linear regression models were used to show the association between the number of symptoms and PCF.

Results: Of the 425 participants, 37% (n = 157) developed PCF; most were women (70%). The median number of symptoms was significantly higher in the PCF group than in the non-PCF group at both time points. In multivariable linear regression models, both sum scores were associated with PCF (acute symptoms: β-estimate per additional symptom [95%-CI]: 0.48 [0.39; 0.57], p < 0.0001); persistent symptoms: β-estimate per additional symptom [95%-CI]: 1.18 [1.02; 1.34], p < 0.0001). The acute symptoms strongest associated with PCF severity were difficulty concentrating, memory problems, dyspnea or shortness of breath on exertion, palpitations, and problems with movement coordination.

Conclusion: Each additional symptom that occurs in COVID-19 increases the likelihood of suffering a higher severity of PCF. Further research is needed to identify the aetiology of PCF.

Source: Schmidbauer L, Kirchberger I, Goßlau Y, Warm TD, Hyhlik-Dürr A, Linseisen J, Meisinger C. The association between the number of symptoms and the severity of Post-COVID-Fatigue after SARS-CoV-2 infection treated in an outpatient setting. J Neurol. 2023 May 23:1–9. doi: 10.1007/s00415-023-11752-9. Epub ahead of print. PMID: 37219607; PMCID: PMC10204671. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204671/ (Full text)