Tag: long covid symptoms

Neurologic manifestations of long COVID differ based on acute COVID-19 severity

Abstract:

Objective: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients.

Methods: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021.

Results: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were “brain fog” (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.

Interpretation: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions.

Source: Perez Giraldo GS, Ali ST, Kang AK, Patel TR, Budhiraja S, Gaelen JI, Lank GK, Clark JR, Mukherjee S, Singer T, Venkatesh A, Orban ZS, Lim PH, Jimenez M, Miller J, Taylor C, Szymanski AL, Scarpelli J, Graham EL, Balabanov RD, Barcelo BE, Cahan JG, Ruckman K, Shepard AG, Slutzky MW, LaFaver K, Kumthekar PU, Shetty NK, Carroll KS, Ho SU, Lukas RV, Batra A, Liotta EM, Koralnik IJ. Neurologic manifestations of long COVID differ based on acute COVID-19 severity. Ann Neurol. 2023 Mar 26. doi: 10.1002/ana.26649. Epub ahead of print. PMID: 36966460. https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.26649 (Full text available as PDF file)

 

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

Abstract:

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment.

This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC.

The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

Source: Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; RECOVER Mechanistic Pathway Task Force. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 2023 Mar 22;12:e86002. doi: 10.7554/eLife.86002. PMID: 36947108; PMCID: PMC10032659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032659/ (Full text)

An Orthomolecular Protocol for Long COVID

Abstract:

A significant number of COVID-19 patients suffer from SARS-CoV-2 post-acute chronic sequelae, also known as post-COVID syndrome or long COVID. These patients report a broad range of persistent and debilitating symptoms such as fatigue, brain fog, pain, breathlessness, and dysrhythmias. These chronic symptoms are believed to be a consequence of excessive production of reactive oxygen species (ROS), inflammation, tissue damage, and mitochondrial dysfunction. Patients at higher risk of long-term sequelae are those who experienced severe COVID-19 infection, are immunocompromised and likely have depleted reserves of biological factors and micronutrients necessary for prompt recovery.

Based on biochemical principles and studies in conditions that share common traits with long COVID patients such as chronic fatigue syndrome and fibromyalgia, symptom relief and sustained recovery can be expected by administering an orthomolecular protocol consisting of a combination of precursors, cofactors, and biological response modifiers.

Source: Gonzalez MJ et al. (2023) An Orthomolecular Protocol for Long-COVID. J Orthomol Med. 38(1) https://www.researchgate.net/publication/369328211_An_Orthomolecular_Protocol_for_Long_COVID (Full text)

Immunometabolic rewiring in long COVID patients with chronic headache

Abstract:

Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. L

ong COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache.

Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.

Source: Foo SS, Chen W, Jung KL, Azamor T, Choi UY, Zhang P, Comhair SA, Erzurum SC, Jehi L, Jung JU. Immunometabolic rewiring in long COVID patients with chronic headache. bioRxiv [Preprint]. 2023 Mar 6:2023.03.06.531302. doi: 10.1101/2023.03.06.531302. PMID: 36945569; PMCID: PMC10028820. https://www.biorxiv.org/content/10.1101/2023.03.06.531302v1.full (Full text)

Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people

Abstract:

Objectives: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination.

Design: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale).

Results: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP.

Conclusions: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated.

Source: Pinto Pereira SM, Nugawela MD, Rojas NK, Shafran R, McOwat K, Simmons R, Ford T, Heyman I, Ladhani SN, Cheung EY, Fox-Smith L, Dalrymple E, Stephenson T. Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people. Arch Dis Child. 2023 Apr;108(4):289-295. doi: 10.1136/archdischild-2022-324656. Epub 2023 Jan 4. PMID: 36599625. https://adc.bmj.com/content/108/4/289.long (Full text)

Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis

Abstract:

Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19’s long-term effects at 12 months and above.

We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976.

At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.

Source: Mudgal S K, Gaur R, Rulaniya S, et al. (March 18, 2023) Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis. Cureus 15(3): e36325. doi:10.7759/cureus.36325 https://www.cureus.com/articles/143288-pooled-prevalence-of-long-covid-19-symptoms-at-12-months-and-above-follow-up-period-a-systematic-review-and-meta-analysis#!/ (Full text)

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series

Abstract:

Introduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

Materials and methods: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers.

Results: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%).

Conclusion: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Source: Bocci T, Bertini A, Campiglio L, Botta S, Libelli G, Guidetti M, Priori A. Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series. Neurol Sci. 2023 Apr;44(4):1147-1153. doi: 10.1007/s10072-023-06637-8. Epub 2023 Feb 3. PMID: 36735149; PMCID: PMC9896447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896447/ (Full study)

Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program

Abstract:

Objectives: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.

Materials and methods: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls.

Results: We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise.

Discussion: Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes.

Conclusion: We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.

Source: Lorman V, Rao S, Jhaveri R, Case A, Mejias A, Pajor NM, Patel P, Thacker D, Bose-Brill S, Block J, Hanley PC, Prahalad P, Chen Y, Forrest CB, Bailey LC, Lee GM, Razzaghi H. Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program. JAMIA Open. 2023 Mar 14;6(1):ooad016. doi: 10.1093/jamiaopen/ooad016. PMID: 36926600; PMCID: PMC10013630. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013630/ (Full text)

Pain Management in the Post-COVID Era-An Update: A Narrative Review

Abstract:

An extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is demonstrated, the term “long-COVID” is used.

Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches.

All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID.

Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on the patients, health care systems, and society as well. Therefore, it is important that patients with chronic pain receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description about the post-COVID pain and to explore the impact of long COVID-19 on chronic pain patients, and also to give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.

Source: El-Tallawy SN, Perglozzi JV, Ahmed RS, Kaki AM, Nagiub MS, LeQuang JK, Hadarah MM. Pain Management in the Post-COVID Era-An Update: A Narrative Review. Pain Ther. 2023 Apr;12(2):423-448. doi: 10.1007/s40122-023-00486-1. Epub 2023 Feb 28. PMID: 36853484; PMCID: PMC9971680. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971680/ (Full text)

Epidemiological and clinical perspectives of long COVID syndrome

Abstract:

Long COVID, or post-acute COVID-19 syndrome, is characterized by multi-organ symptoms lasting 2+ months after initial COVID-19 virus infection. This review presents the current state of evidence for long COVID syndrome, including the global public health context, incidence, prevalence, cardiopulmonary sequelae, physical and mental symptoms, recovery time, prognosis, risk factors, rehospitalization rates, and the impact of vaccination on long COVID outcomes. Results are presented by clinically relevant subgroups.

Overall, 10-35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic stress disorder, memory loss, and difficulty concentrating. Delineating these issues will be crucial to inform appropriate post-pandemic health policy and protect the health of COVID-19 survivors, including potentially vulnerable or underrepresented groups. Directed to policymakers, health practitioners, and the general public, we provide recommendations and suggest avenues for future research with the larger goal of reducing harms associated with long COVID syndrome.

Source: Huerne K, Filion KB, Grad R, Ernst P, Gershon AS, Eisenberg MJ. Epidemiological and clinical perspectives of long COVID syndrome. Am J Med Open. 2023 Jun;9:100033. doi: 10.1016/j.ajmo.2023.100033. Epub 2023 Jan 18. PMID: 36685609; PMCID: PMC9846887. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846887/ (Full text)