Tag: 2023

Myalgic Encephalomyelitis-Chronic Fatigue Syndrome Common Data Element item content analysis

Abstract:

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem chronic disease estimated to affect 836,000-2.5 million individuals in the United States. Persons with ME/CFS have a substantial reduction in their ability to engage in pre-illness levels of activity. Multiple symptoms include profound fatigue, post-exertional malaise, unrefreshing sleep, cognitive impairment, orthostatic intolerance, pain, and other symptoms persisting for more than 6 months. Diagnosis is challenging due to fluctuating and complex symptoms. ME/CFS Common Data Elements (CDEs) were identified in the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) Common Data Element Repository. This study reviewed ME/CFS CDEs item content.

Methods: Inclusion criteria for CDEs (measures recommended for ME/CFS) analysis: 1) assesses symptoms; 2) developed for adults; 3) appropriate for patient reported outcome measure (PROM); 4) does not use visual or pictographic responses. Team members independently reviewed CDEs item content using the World Health Organization International Classification of Functioning, Disability and Health (ICF) framework to link meaningful concepts.

Results: 119 ME/CFS CDEs (measures) were reviewed and 38 met inclusion criteria, yielding 944 items linked to 1503 ICF meaningful concepts. Most concepts linked to ICF Body Functions component (b-codes; n = 1107, 73.65%) as follows: Fatiguability (n = 220, 14.64%), Energy Level (n = 166, 11.04%), Sleep Functions (n = 137, 9.12%), Emotional Functions (n = 131, 8.72%) and Pain (n = 120, 7.98%). Activities and Participation concepts (d codes) accounted for a smaller percentage of codes (n = 385, 25.62%). Most d codes were linked to the Mobility category (n = 69, 4.59%) and few items linked to Environmental Factors (e codes; n = 11, 0.73%).

Discussion: Relatively few items assess the impact of ME/CFS symptoms on Activities and Participation. Findings support development of ME/CFS-specific PROMs, including items that assess activity limitations and participation restrictions. Development of psychometrically-sound, symptom-based item banks administered as computerized adaptive tests can provide robust assessments to assist primary care providers in the diagnosis and care of patients with ME/CFS.

Source: Slavin MD, Bailey HM, Hickey EJ, Vasudevan A, Ledingham A, Tannenbaum L, Bateman L, Kaufman DL, Peterson DL, Ruhoy IS, Systrom DM, Felsenstein D, Kazis LE. Myalgic Encephalomyelitis-Chronic Fatigue Syndrome Common Data Element item content analysis. PLoS One. 2023 Sep 12;18(9):e0291364. doi: 10.1371/journal.pone.0291364. PMID: 37698999. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291364 (Full text)

Influence of end-tidal CO2 on cerebral blood flow during orthostatic stress in controls and adults with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Brain perfusion is sensitive to changes in CO2 levels (CO2 reactivity). Previously, we showed a pathological cerebral blood flow (CBF) reduction in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients during orthostatic stress. Limited data are available on the relation between CO2 and CBF changes in ME/CFS patients. Therefore, we studied this relation between ME/CFS patients and healthy controls (HC) during tilt testing.

In this retrospective study, supine and end-tilt CBF, as measured by extracranial Doppler flow, were compared with PET CO2 data in female patients either with a normal heart rate and blood pressure (HR/BP) response or with postural orthostatic tachycardia syndrome (POTS), and in HC. Five hundred thirty-five female ME/CFS patients and 34 HC were included.

Both in supine position and at end-tilt, there was a significant relation between CBF and PET CO2 in patients (p < 0.0001), without differences between patients with a normal HR/BP response and with POTS. The relations between the %CBF change and the PET CO2 reduction were both significant in patients and HC (p < 0.0001 and p = 0.0012, respectively).

In a multiple regression analysis, the patient/HC status and PET CO2 predicted CBF. The contribution of the PET CO2 to CBF changes was limited, with low adjusted R2 values. In female ME/CFS patients, CO2 reactivity, as measured during orthostatic stress testing, is similar to that of HC and is independent of the type of hemodynamic abnormality. However, the influence of CO2 changes on CBF changes is modest in female ME/CFS patients.

Source: van Campen CLMC, Rowe PC, Verheugt FWA, Visser FC. Influence of end-tidal CO2 on cerebral blood flow during orthostatic stress in controls and adults with myalgic encephalomyelitis/chronic fatigue syndrome. Physiol Rep. 2023 Sep;11(17):e15639. doi: 10.14814/phy2.15639. PMID: 37688420; PMCID: PMC10492011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10492011/ (Full text)

The Potential Role of Hypothalamic Phospholipid Liposomes in the Supportive Therapy of Some Manifestations of Post-COVID-19 Condition: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Brain Fog

Abstract:

Post-COVID-19 condition (commonly known as Long COVID) is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. Cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of the pathophysiology of Post-COVID-19 condition (PCC).

Given the substantial lack of specific drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes, which have been on the market for several years as adjuvant therapy for cerebral metabolic alterations resulting from neuroendocrine disorders, might represent a potential option in an overall therapeutic strategy that aims to control PCC-associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their potential effectiveness in PCC. Our initial clinical experience seems to corroborate this rationale. Further controlled clinical research is warranted in order to verify this hypothesis.

Source: Menichetti F. The Potential Role of Hypothalamic Phospholipid Liposomes in the Supportive Therapy of Some Manifestations of Post-COVID-19 Condition: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Brain Fog. J Clin Med. 2023 Aug 23;12(17):5478. doi: 10.3390/jcm12175478. PMID: 37685544; PMCID: PMC10488182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10488182/ (Full text)

SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)

Abstract:

Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a ‘reservoir’. This reservoir could modulate host immune responses or release viral proteins into the circulation.

Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.

Source: Proal AD, VanElzakker MB, Aleman S, Bach K, Boribong BP, Buggert M, Cherry S, Chertow DS, Davies HE, Dupont CL, Deeks SG, Eimer W, Ely EW, Fasano A, Freire M, Geng LN, Griffin DE, Henrich TJ, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter MM, Peluso MJ, Pretorius E, Price DA, Putrino D, Scheuermann RH, Tan GS, Tanzi RE, VanBrocklin HF, Yonker LM, Wherry EJ. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat Immunol. 2023 Sep 4. doi: 10.1038/s41590-023-01601-2. Epub ahead of print. PMID: 37667052. https://www.nature.com/articles/s41590-023-01601-2 (Full text)

How post-infection status could lead to the increasing risks of chronic fatigue syndrome and the potential mechanisms: A 17-year population based Cohort study

Abstract:

Background: Serological studies have suggested that viruses and atypical pathogens are associated with CFS, but no study has focused on typical and common pathogens. This study aims to assess the association of infections with a variety of common pathogens with the risk of CFS and provide evidence for the hypothesis that infection triggers CFS.

Methods: The nested case-control study identified 2,000,000 adult patients from a nationwide population-based health insurance claims database from January 1, 2000, to December 31, 2017. Each case with a diagnosis of infection by pathogens was matched with one control using a propensity score. Patients with more than one potential pathogen, younger than 20 years old, or with a history of CFS or infection with certain pathogens before the index date were excluded. Univariate and multivariate Cox proportional hazard models were applied to estimate the HR, aHR, and corresponding 95% CI. The multivariate analysis had adjustments for age, sex, comorbidities, and medication confounders.

Results: A total of 395,811 cases with 1: 1 matched controls were included (58.2% female; mean age [standard deviation], 44.15 [17.02]). Among these, the aHR of the pathogen cohort was 1.5 (95% CI, 1.47 to 1.54). Pathogens were positively correlated with CFS, including influenza, candida and others.

Conclusion: The findings of this study demonstrate the association between CFS and infection with common pathogens, including bacteria, virus and fungi.

Source: Hsun Chang; Chien-Feng Kuo; Teng-Shun Yu; Liang-Yin Ke; Chung-Lieh Hung; Shin-Yi Tsai. How post-infection status could lead to the increasing risks of chronic fatigue syndrome and the potential mechanisms: A 17-year population based Cohort study. Research Square, August 30, 2023. https://assets.researchsquare.com/files/rs-3289981/v1/55890598-6f0d-4f73-a9f4-5349e07baac0.pdf (Full text)

Cardiovascular risk factors predict who should have echocardiographic evaluation in long COVID

Abstract:

Background: The need for echocardiograms among patients with long COVID is debatable. Our aim was to evaluate the prevalence of left ventricular (LV) dysfunction and identify predictors.
Methods: We conducted a cross-sectional study and included all consecutive patients enrolled in our post-COVID clinic. We included patients who had an echocardiogram and had no previous known heart disease. We defined LV dysfunction as a low ejection fraction or grade II to grade III diastolic dysfunction on an echocardiogram with evidence of elevated filling pressures. We calculated the prevalence of heart disease and predictors of heart disease using logistic regression.
Results: We included 217 post-COVID patients enrolled in the clinic. The prevalence of LV dysfunction is 24%;95% CI 18-30. Predictors of heart disease include older age and a previous history of hypertension and diabetes or having a intermediate or high ASCVD score. Patients with low ASCVD score did not have low ejection fraction on the screening echocardiograms.
Conclusion: Our study found a considerable number of patients with LV dysfunction. Older patients with cardiovascular risk factors are at risk of long COVID associated heart disease.
Source: Leonardo Tamariz, Mathew Ryan, George Marzouka R, et al. Cardiovascular risk factors predict who should have echocardiographic evaluation in long COVID. Authorea. August 23, 2023. https://www.authorea.com/doi/full/10.22541/au.169277562.22633945 (Full text available as download)

Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19

Abstract:

Purpose: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19.

Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality.

Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)].

Conclusion: In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

Source: Shaseb E, Ghaffary S, Garjani A, Zoghi E, Maleki Dizaji N, Soltani S, Sarbakhsh P, Somi MH, Valizadeh P, Taghizadieh A, Faghihdinevari M, Varshochi M, Naghily B, Bayatmakoo Z, Saleh P, Taghizadeh S, Haghdoost M, Owaysi H, Ravanbakhsh Ghavghani F, Tarzamni MK, Moradi R, Javan Ali Azar F, Shabestari Khiabani S, Ghazanchaei A, Hamedani S, Hatefi S. Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19. Adv Pharm Bull. 2023 Jul;13(3):621-626. doi: 10.34172/apb.2023.066. Epub 2022 Jul 2. PMID: 37646067; PMCID: PMC10460805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460805/ (Full text)

SARS-CoV-2-Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19

Abstract:

Background and objectives: Millions of Americans were exposed to SARS-CoV-2 early in the pandemic but could not get diagnosed with COVID-19 due to testing limitations. Many have developed a postviral syndrome (PVS) including neurologic manifestations similar to those with postacute sequelae of SARS-CoV-2 infection (Neuro-PASC). Owing to those circumstances, proof of SARS-CoV-2 infection was not required for evaluation at Northwestern Medicine’s Neuro COVID-19 clinic. We sought to investigate clinical and immunologic findings suggestive of SARS-CoV-2 exposure in patients with PVS.

Methods: We measured SARS-CoV-2-specific humoral and cell-mediated immune responses against Nucleocapsid and Spike proteins in 29 patients with PVS after suspected COVID-19, 32 confirmed age-matched/sex-matched Neuro-PASC (NP) patients, and 18 unexposed healthy controls. Neurologic symptoms and signs, comorbidities, quality of life, and cognitive testing data collected during clinic visits were studied retrospectively.

Results: Of 29 patients with PVS, 12 (41%) had detectable humoral or cellular immune responses consistent with prior exposure to SARS-CoV-2. Of 12 PVS responders (PVS+), 75% harbored anti-Nucleocapsid and 50% harbored anti-Spike responses. Patients with PVS+ had similar neurologic symptoms as patients with NP, but clinic evaluation occurred 5.3 months later from the time of symptom onset (10.7 vs 5.4 months; p = 0.0006). Patients with PVS+ and NP had similar subjective impairments in quality of life measures including cognitive function and fatigue. Patients with PVS+ had similar results in objective cognitive measures of processing speed, attention, and executive function and better results in working memory than patients with NP.

Discussion: Antibody and T-cell assays showed evidence of prior SARS-CoV-2 exposure in approximately 40% of the PVS group. Three-quarters of patients with PVS+ had detectable anti-Nucleocapsid and one-half anti-Spike responses, highlighting the importance of multitargeted COVID-19 immunologic evaluation and the limitations of commercially available diagnostic tests. Despite their persistent symptoms, lack of COVID-19 diagnosis likely delayed clinical care in patients with PVS. Our data suggest that millions of Americans presenting with PVS resembling Neuro-PASC were indeed exposed to SARS-CoV-2 at the beginning of the pandemic, and they deserve the same access to care and inclusion in research studies as patients with NP with confirmed COVID-19 diagnosis.

Source:Orban ZS, Visvabharathy L, Perez Giraldo GS, Jimenez M, Koralnik IJ. SARS-CoV-2-Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19. Neurol Neuroimmunol Neuroinflamm. 2023 Aug 23;10(6):e200159. doi: 10.1212/NXI.0000000000200159. PMID: 37612134; PMCID: PMC10448973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448973/ (Full text)

Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults — United States, December 2020–March 2023

Summary:

What is already known about this topic? Post-COVID conditions, or long COVID, can persist for months or years after an acute COVID-19 illness and can include emergence of new symptoms or the occurrence of symptoms that come and go.

What is added by this report? In a multicenter study of adults with a COVID-like illness, symptom prevalence decreased over time after the acute illness. Approximately 16% of adults with COVID-like symptoms reported persistent symptoms 12 months after a positive or negative SARS-CoV-2 test result. At 3, 6, 9, and 12 months after testing, some symptomatic persons had ongoing symptoms, and others had emerging symptoms not reported during the previous period.

What are the implications for public health practice? Health care providers should be aware that symptoms can persist, emerge, reemerge, or resolve after COVID-like illness and are not unique to COVID-19 or to post-COVID conditions.

Abstract:

To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration–approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months.

Prevalence of any symptom decreased substantially between baseline and the 3-month follow-up, from 98.4% to 48.2% for persons who received a positive SARS-CoV-2 test results (COVID test–positive participants) and from 88.2% to 36.6% for persons who received negative SARS-CoV-2 test results (COVID test–negative participants).

Persistent symptoms decreased through 12 months; no difference between the groups was observed at 12 months (prevalence among COVID test–positive and COVID test–negative participants = 18.3% and 16.1%, respectively; p>0.05).

Both groups reported symptoms that emerged or reemerged at 6, 9, and 12 months. Thus, these symptoms are not unique to COVID-19 or to post-COVID conditions. Awareness that symptoms might persist for up to 12 months, and that many symptoms might emerge or reemerge in the year after COVID-like illness, can assist health care providers in understanding the clinical signs and symptoms associated with post-COVID–like conditions.

Source: Montoy JC, Ford J, Yu H, et al. Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults — United States, December 2020–March 2023. MMWR Morb Mortal Wkly Rep 2023;72:859–865. DOI: http://dx.doi.org/10.15585/mmwr.mm7232a2 (Full text)

Long COVID and Significant Activity Limitation Among Adults, by Age — United States, June 1–13, 2022, to June 7–19, 2023

Summary:

What is already known about this topic? Long COVID includes a wide range of ongoing symptoms that can last for weeks, months, or years following SARS-CoV-2 infection.

What is added by this report? Prevalence of long COVID among noninstitutionalized U.S. adults aged ≥18 years decreased from 7.5% (95% CI = 7.1–7.9) during June 1–13, 2022 to 6.0% (95% CI = 5.7–6.3) during June 7–19, 2023 and from 18.9% (95% CI = 17.9–19.8) to 11.0% (95% CI = 10.4–11.6) among adults reporting previous COVID-19. After an initial decline, prevalence remained unchanged beginning January 4–16, 2023. Approximately one quarter of adults with long COVID report significant activity limitations.

What are the implications for public health practice? COVID-19 prevention efforts, including staying up to date with recommended COVID-19 vaccination and planning for long COVID symptom management and health care service needs, remain important.

Abstract:

Long COVID is a condition encompassing a wide range of health problems that emerge, persist, or return following COVID-19. CDC analyzed national repeat cross-sectional Household Pulse Survey data to estimate the prevalence of long COVID and significant related activity limitation among U.S. adults aged ≥18 years by age group.

Data from surveys completed between June 1–13, 2022, and June 7–19, 2023, indicated that long COVID prevalence decreased from 7.5% (95% CI = 7.1–7.9) to 6.0% (95% CI = 5.7–6.3) among the overall U.S. adult population, irrespective of history of previous COVID-19, and from 18.9% (95% CI = 17.9–19.8) to 11.0% (95% CI = 10.4–11.6) among U.S. adults reporting previous COVID-19. Among both groups, prevalence decreased from June 1–13, 2022, through January 4–16, 2023, before stabilizing.

When stratified by age, only adults aged <60 years experienced significant rates of decline (p<0.01). Among adults reporting previous COVID-19, prevalence decreased among those aged 30–79 years through fall or winter and then stabilized.

During June 7–19, 2023, 26.4% (95% CI = 24.0–28.9) of adults with long COVID reported significant activity limitation, the prevalence of which did not change over time.

These findings help guide the ongoing COVID-19 prevention efforts and planning for long COVID symptom management and future health care service needs.

Source:  Ford ND, Slaughter D, Edwards D, et al. Long COVID and Significant Activity Limitation Among Adults, by Age — United States, June 1–13, 2022, to June 7–19, 2023. MMWR Morb Mortal Wkly Rep 2023;72:866–870. DOI: http://dx.doi.org/10.15585/mmwr.mm7232a3 (Full text)