Tag: long Covid

Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can be triggered by infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the impact of the coronavirus disease 2019 (COVID-19) pandemic on ME/CFS prevalence is not well characterized.

Methods: In this population-based cross-sectional study, we enrolled a stratified random sample of 9,825 adult participants in the Kaiser Permanente Northern California (KPNC) integrated health system from July to October 2022 to assess overall ME/CFS-like illness prevalence and the proportion that were identified following COVID-19 illness. We used medical record and survey data to estimate the prevalence of ME/CFS-like illness based on self-reported symptoms congruent with the 2015 Institute of Medicine ME/CFS criteria. History of COVID-19 was based on a positive SARS-CoV-2 nucleic acid amplification test or ICD-10 diagnosis code in the medical record, or self-report of prior COVID-19 on a survey.

Results: Of 2,745,374 adults in the eligible population, an estimated 45,892 (95% confidence interval [CI]: 32,869, 58,914) or 1.67% (CI 1.20%, 2.15%) had ME/CFS-like illness. Among those with ME/CFS-like illness, an estimated 14.12% (CI 3.64%, 24.6%) developed the illness after COVID-19. Among persons who had COVID-19, those with ME/CFS-like illness after COVID-19 were more likely to be unvaccinated and to have had COVID-19 before June 1, 2021. All persons with ME/CFS-like illness had significant impairment in physical, mental, emotional, social, and occupational functioning compared to persons without ME/CFS-like illness.

Conclusions: In a large, integrated health system, 1.67% of adults had ME/CFS-like illness and 14.12% of all persons with ME/CFS-like illness developed it after COVID-19. Though COVID-19 did not substantially increase ME/CFS-like illness in the KPNC population during the study time period, ME/CFS-like illness nevertheless affects a notable portion of this population and is consistent with estimates of ME/CFS prevalence in other populations. Additional attention is needed to improve awareness, diagnosis, and treatment of ME/CFS.

Source: Wood MS, Halmer N, Bertolli J, Amsden LB, Nugent JR, Lin JS, Rothrock G, Nadle J, Chai SJ, Cope JR, Champsi JH, Yang J, Unger ER, Skarbinski J; for STOP-ME/CFS and COVID-SELECT. Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey. PLoS One. 2024 Sep 18;19(9):e0309810. doi: 10.1371/journal.pone.0309810. PMID: 39292671; PMCID: PMC11410243. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410243/ (Full text)

How Long is Long COVID? Evaluation of Long-Term Health Status in Individuals Discharged from a Specialist Community Long COVID Service

Abstract:

Background: Post COVID-19 syndrome or Long Covid (LC) is a novel fluctuating condition with a protracted course in some patients. Specialist LC services have been operational in the UK since 2020 and deal with a high caseload of patients. Aims: To evaluate long-term outcomes in patients discharged from a community-based LC specialist service.

Methods: A service evaluation study that included patients who were well engaged in the services [completed the standard Patient Reported Outcome Measures (PROMs) and received intervention from clinician(s)] and had been discharged for at least 3 months from the service. They consented to the study and completed standard PROMs: COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), EQ-5D-5L, and National Institute for Health and Care Excellence (NICE) criteria for Myalgia Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS).

Results: Out of 460 patients contacted, 112 (average of 37.6 months since infection and 9.8 months post-discharge) completed the PROMs. 90.2% patients continued to experience LC symptoms and disability and had not returned to their pre-COVID health status. The average EQ-5D-5L index score was 0.53 (SD 0.29) highlighting a significant disability and that LC had become a long-term condition (LTC) in majority of patients who responded to the survey. 43% patients met the criteria for suspected ME/CFS.

Conclusion: A proportion of LC patients develop Persistent Long Covid (PLC) consistent with a LTC and had a significant overlap with ME/CFS.

Source: Bodey, R.; Grimaldi, J.; Tait, H.; Godfrey, B.; Witton, S.; Sharda, J.; Tarrant, R.; Sivan, M. How Long is Long COVID? Evaluation of Long-Term Health Status in Individuals Discharged from a Specialist Community Long COVID Service. Preprints 2024, 2024090813. https://doi.org/10.20944/preprints202409.0813.v1 https://www.preprints.org/manuscript/202409.0813/v1 (Full text available as PDF file)

Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study

Summary:

Background: Children can develop Long Covid, however long term outcomes and their predictors are poorly described in these patients. The primary aim is to describe characteristics and predictors of Long Covid in children assessed in-clinics up to 36 months post-SARS-CoV-2 infection, as well as investigate the role of vaccines in preventing Long Covid, risk of reinfections and development of autoimmune diseases.

Methods: Children aged 0–18 years old with confirmed SARS-CoV-2 infection were invited for a prospective follow-up assessment at a peadiatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12-, 18-, 24- and 36-months post-infection onset, between 01/02/2020 and 28/02/2024). Long Covid was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection.

Findings: 1319 patients were initially included, 1296 reached the 3 months follow-up or more. Of the patients who underwent multiple follow-ups, 23.2% (301), 169 (13.2%), 89 (7.9%), 67 (6.1%), 47 (7.1%) were diagnosed with Long Covid at 3-6-12-18-24 months, respectively For the primary outcome of Long Covid at three months, age >12 years (P < 0.001, OR 11.33, 95% CI 4.2; 15.15), comorbidities (P = 0.008, OR 1.83, 95% CI 1.06; 2.44), being infected with original variants (P < 0.001, OR 4.77, 95% CI 2.46; 14.47), female sex (P < 0.001, OR 1.62, 95% CI 1.02; 1.89) were statistically significant risk factors. Age >12 years (P = 0.002, OR 9.37, 95% CI 1.58; 8.64), and infection with original (P = 0.012, OR 3.52, 95% CI 1.32; 8.64) and alfa (P < 0.001, OR 4.09, 95% CI 2.01; 8.3) SARS-CoV-2 variants remained statistically significant risk factors for Long Covid duration for at least 18 months. Vaccination was associated with a lower risk of long covid at 3, 6 and 12 months for older children and a lower risk of reinfections. Being infected with the original SARS-CoV-2 variant was associated with a higher risk of new-onset autoimmune diseases ((P = 0.035, 95% CI 1.12; 2.4). One patient was diagnosed with Long Covid after a re-infection.

Interpretation: This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics.

Source: Camporesi, Anna et al. Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study.  eClinicalMedicine, Volume 76, 102815 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00394-8/fulltext

Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated.

Purpose and methods: In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM.

Results: Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.

Source: Haunhorst S, Dudziak D, Scheibenbogen C, Seifert M, Sotzny F, Finke C, Behrends U, Aden K, Schreiber S, Brockmann D, Burggraf P, Bloch W, Ellert C, Ramoji A, Popp J, Reuken P, Walter M, Stallmach A, Puta C. Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome. Infection. 2024 Sep 6. doi: 10.1007/s15010-024-02386-8. Epub ahead of print. PMID: 39240417. https://link.springer.com/article/10.1007/s15010-024-02386-8 (Full text)

Two-Year Longitudinal Study Reveals That Long COVID Symptoms Peak and Quality of Life Nadirs at 6–12 Months Postinfection

Abstract:

Background: Few longitudinal studies available characterize long COVID outcomes out to 24 months, especially in people with nonsevere acute coronavirus disease 2019 (COVID-19). This study sought to prospectively characterize incidence and duration of long COVID symptoms and their association with quality of life (QoL) from 1–24 months after mild-to-moderate COVID-19 using validated tools in a diverse cohort of unvaccinated people infected with SARS-CoV-2 in 2020.

Methods: At 1–3, 6, 12, 18, and 24 months post-COVID-19, 70 participants had orthostatic vital signs measured, provided blood, and completed surveys characterizing symptoms, QoL, and return to pre-COVID-19 health and activities using validated tools (FLU-PRO+, Fatigue Severity Scale, Insomnia Severity Index, General Practitioner Assessment of Cognition, Patient Health Questionnaire Depression 8-Item, Generalized Anxiety Disorder 7-Item, 36-Item Short-Form Health Survey, EuroQol EQ-5D-5L).

Results: During the study period, 33% of participants experienced long COVID (had not returned to pre-COVID-19 health status and reported at least 1 symptom >90 days postinfection); 8% had not returned to their pre-COVID-19 health status 24 months postinfection. Long COVID symptoms peaked 6 months post-COVID-19, frequently causing activity limitations. Having long COVID was significantly associated with decreased QoL in multiple domains. Frequencies of orthostatic hypotension and tachycardia reflected levels reported in the general population. Within-person weight increased significantly between months 1 and 6. Long COVID was associated with pre-COVID-19 obesity and hyperlipidemia, but not with high-sensitivity C-reactive protein levels 1–3 months postinfection.

Conclusions: Long COVID occurs in a significant proportion of unvaccinated people, even if the acute illness was not severe. Long COVID prevalence peaked 6–12 months post-COVID-19, and a small proportion of participants still reported not returning to their pre-COVID-19 health status 24 months post-COVID-19.

Source: Demko ZO, Yu T, Mullapudi SK, Varela Heslin MG, Dorsey CA, Payton CB, Tornheim JA, Blair PW, Mehta SH, Thomas DL, Manabe YC, Antar AAR. Two-Year Longitudinal Study Reveals That Long COVID Symptoms Peak and Quality of Life Nadirs at 6-12 Months Postinfection. Open Forum Infect Dis. 2024 Mar 6;11(3):ofae027. doi: 10.1093/ofid/ofae027. PMID: 38449921; PMCID: PMC10917418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917418/ (Full text)

A multimodal approach for treating post-acute infectious syndrome

Abstract:

Long-term complications, such as extensive fatigue and cognitive issues, are known from various infections, including SARS-CoV-2, influenza
virus, or Borrelia burgdorferi. The pathology is mostly unknown and differs between patients. Unfortunately, there is currently no common and
effective treatment. In this perspective, we imply that post-acute infectious syndromes are due to a variety of factors, including among others
diminished tissue perfusion, tissue infiltration by viruses, inflammation, and oxidative stress, and that not one specific biomarker can be used
to measure these syndromes. Thus, we suggest that a score based on a number of criteria/factors should be used to assess post-acute infectious
syndromes.

Consequently, probably not one single treatment can be used to treat this group of patients, and we suggest a multimodal
treatment regimen comprising a combination of pharmacotherapy, such as metformin and naltrexone with anti-inflammatory effects,
alongside physical therapies such as extracorporeal apheresis and transcutaneous neurotherapy. This combined approach aims to reduce
biomarker levels and enhance cognitive functions. This implies that a reset of the systems can be achieved by a multimodal approach based on a
score for post-acute infectious syndromes.

Source:  Charlotte Steenblock, Nicole Toepfner, Yannick P. Kok, Philip Mavberg, Horst Bruckmoser, Alfons Breu, Johannes Korth, Harald Heidecke, Milo A. Puhan, and Stefan R. Bornstein. A multimodal approach for treating post-acute infectious syndrome. Brain Medicine (2024) 1, 1–7; doi: https://doi.org/10.61373/bm024p.0064; Published online: 30 August 2024. https://bm.genomicpress.com/wp-content/uploads/2024/08/BM0064-Steenblock-2024.pdf (Full text)

Long COVID Is Not a Functional Neurologic Disorder

Abstract:

Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions. However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID.

The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID.

We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings.

Source: Davenport TE, Blitshteyn S, Clague-Baker N, Davies-Payne D, Treisman GJ, Tyson SF. Long COVID Is Not a Functional Neurologic Disorder. J Pers Med. 2024 Jul 29;14(8):799. doi: 10.3390/jpm14080799. PMID: 39201991. https://www.mdpi.com/2075-4426/14/8/799 (Full text)

The association between prolonged SARS-CoV-2 symptoms and work outcomes

Abstract:

While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work.

The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed a baseline and three-month electronic survey. At three months post-infection, 40.8% of participants reported at least one SARS-CoV-2 symptom and 9.6% of participants reported five or more SARS-CoV-2 symptoms.

When asked about missed work due to their SARS-CoV-2 infection at three months, 7.2% of participants reported missing ≥10 workdays and 13.9% of participants reported not returning to work since their infection. At three months, participants with ≥5 symptoms had a higher adjusted odds ratio of missing ≥10 workdays (2.96, 95% CI 1.81–4.83) and not returning to work (2.44, 95% CI 1.58–3.76) compared to those with no symptoms. Prolonged SARS-CoV-2 symptoms were common, affecting 4-in-10 participants at three-months post-infection, and were associated with increased odds of work loss, most pronounced among adults with ≥5 symptoms at three months.

Despite the end of the federal Public Health Emergency for COVID-19 and efforts to “return to normal”, policymakers must consider the clinical and economic implications of the COVID-19 pandemic on people’s employment status and work absenteeism, particularly as data characterizing the numerous health and well-being impacts of Long COVID continue to emerge. Improved understanding of risk factors for lost work time may guide efforts to support people in returning to work.

Source: Venkatesh AK, Yu H, Malicki C, Gottlieb M, Elmore JG, Hill MJ, et al. (2024) The association between prolonged SARS-CoV-2 symptoms and work outcomes. PLoS ONE 19(7): e0300947. https://doi.org/10.1371/journal.pone.0300947 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0300947 (Full text)

Characterizing Long COVID in Children and Adolescents

Key Points:

Question  What prolonged symptoms experienced by youth are most associated with SARS-CoV-2 infection?

Findings  Among 5367 participants in the RECOVER-Pediatrics cohort study, 14 symptoms in both school-age children (6-11 years) and adolescents (12-17 years) were more common in those with vs without SARS-CoV-2 infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. Empirically derived indices for PASC research and associated clustering patterns were developed.

Meaning  This study developed research indices for characterizing pediatric PASC. Symptom patterns were similar but distinguishable between school-age children and adolescents, highlighting the importance of characterizing PASC separately in different age groups.

Abstract

Importance  Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.

Objective  To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.

Design, Setting, and Participants  Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.

Exposure  SARS-CoV-2 infection.

Main Outcomes and Measures  PASC and 89 prolonged symptoms across 9 symptom domains.

Results  A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise–related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.

Conclusions and Relevance This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Source: Rachel S. Gross, MD, MS; Tanayott Thaweethai, PhD; Lawrence C. Kleinman, MD, MPH; et al. JAMA. Published online August 21, 2024. doi:10.1001/jama.2024.12747 https://jamanetwork.com/journals/jama/article-abstract/2822770

Designing and optimizing clinical trials for long COVID

Abstract:

Long COVID is a debilitating, multisystemic illness following a SARS-CoV-2 infection whose duration may be indefinite. Over four years into the pandemic, little knowledge has been generated from clinical trials. We analyzed the information available on ClinicalTrials.gov, and found that the rigor and focus of trials vary widely, and that the majority test non-pharmacological interventions with insufficient evidence.

We highlight promising trials underway, and encourage the proliferation of clinical trials for treating Long COVID and other infection-associated chronic conditions and illnesses (IACCIs). We recommend several guidelines for Long COVID trials: First, pharmaceutical trials with potentially curative, primary interventions should be prioritized, and both drug repurposing and new drug development should be pursued.

Second, study designs should be both rigorous and accessible, e.g., triple-blinded randomized trials that can be conducted remotely, without participants needing to leave their homes.

Third, studies should have multiple illness comparator cohorts for IACCIs such as myalgic encephalomyelitis (ME/CFS) and dysautonomia, and screen for the full spectrum of symptomatology and pathologies of these illnesses.

Fourth, studies should consider inclusion/exclusion criteria with an eye towards equity and breadth of representation, including participants of all races, ethnicities, and genders most impacted by COVID-19, and including all levels of illness severity.

Fifth, involving patient-researchers in all aspects of studies brings immensely valuable perspectives that will increase the impact of trials. We also encourage the development of efficient clinical trial designs including methods to study several therapies in parallel.

Source: Vogel JM, Pollack B, Spier E, McCorkell L, Jaudon TW, Fitzgerald M, Davis H, Cohen AK. Designing and optimizing clinical trials for long COVID. Life Sci. 2024 Aug 13;355:122970. doi: 10.1016/j.lfs.2024.122970. Epub ahead of print. PMID: 39142505. https://www.sciencedirect.com/science/article/pii/S0024320524005605 (Full text)