Overlapping conditions in Long COVID at a multisite academic center

Abstract:

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.

Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.

Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).

Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.

Source: Grach SL, Dudenkov DV, Pollack B, Fairweather D, Aakre CA, Munipalli B, Croghan IT, Mueller MR, Overgaard JD, Bruno KA, Collins NM, Li Z, Hurt RT, Tal MC, Ganesh R, Knight DTR. Overlapping conditions in Long COVID at a multisite academic center. Front Neurol. 2024 Oct 25;15:1482917. doi: 10.3389/fneur.2024.1482917. PMID: 39524912; PMCID: PMC11543549. https://pmc.ncbi.nlm.nih.gov/articles/PMC11543549/ (Full text)

Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study

Abstract:

Background: Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity.

Methods: We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented.

Results: 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen’s d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident.

Conclusions: More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.

Source: Fall EA, Chen Y, Lin JS, Issa A, Brimmer DJ, Bateman L, Lapp CW, Podell RN, Natelson BH, Kogelnik AM, Klimas NG, Peterson DL, Unger ER; MCAM Study Group. Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study. BMC Neurol. 2024 Oct 18;24(1):399. doi: 10.1186/s12883-024-03872-0. PMID: 39425035; PMCID: PMC11488184. https://pmc.ncbi.nlm.nih.gov/articles/PMC11488184/ (Full text)

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation

Abstract:

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological disorder characterized by post-exertional malaise. Despite its clinical relevance, the disease mechanisms of ME/CFS are not fully understood. The previous studies targeting brain function or metabolites have been inconclusive in understanding ME/CFS complexity. We combined single-voxel magnetic resonance spectroscopy (SV-MRS) and functional magnetic resonance imaging (fMRI). Our objectives were to examine the feasibility of the multimodal MRI protocol, identify possible differences between ME/CFS and healthy controls (HCs), and relate MRI findings with clinical symptoms.

Methods: We enrolled 18 female ME/CFS participants (mean age: 39.7 ± 12.0 years) and five HCs (mean age: 45.6 ± 14.5 years). SV-MRS spectra were acquired from three voxels of interest: the anterior cingulate gyrus (ACC), brainstem (BS), and left dorsolateral prefrontal cortex (L-DLPFC). Whole-brain fMRI used n-back task testing working memory and executive function. The feasibility was assessed as protocol completion rate and time. Group differences in brain metabolites and fMRI activation between ME/CFS and HCs were compared and correlated with behavioral and symptom severity measurements.

Results: The completion rate was 100% regardless of participant group without causing immediate fatigue. ME/CFS appeared to show a higher N-Acetylaspartate in L-DLPFC compared to HCs (OR = 8.49, p = 0.040), correlating with poorer fatigue, pain, and sleep quality scores (p‘s = 0.001-0.015). An increase in brain activation involving the frontal lobe and the brainstem was observed in ME/CFS compared to HCs (Z > 3.4, p‘s < 0.010).

Conclusions: The study demonstrates the feasibility of combining MRS and fMRI to capture neurochemical and neurophysiological features of ME/CFS in female participants. Further research with larger cohorts of more representative sampling and follow-ups is needed to validate these apparent differences between ME/CFS and HCs.

Source: Kaur R, Greeley B, Ciok A, Mehta K, Tsai M, Robertson H, Debelic K, Zhang LX, Nelson T, Boulter T, Siu W, Nacul L, Song X. A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation. Medicina (Kaunas). 2024 Aug 22;60(8):1370. doi: 10.3390/medicina60081370. PMID: 39202651. https://www.mdpi.com/1648-9144/60/8/1370 (Full text)

Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment

Abstract:

Objective: To report the prevalence and severity of nonpelvic symptoms for patients with venous-origin chronic pelvic pain (VO-CPP) and to describe outcomes after pelvic vein stenting and embolization.

Methods: We retrospectively reviewed outcomes of 45 women with VO-CPP who underwent treatment with iliac vein stenting and/or embolization. Patients completed symptom-severity questionnaires before and after treatment that assessed for pelvic pain, and multiple other symptoms, including brain fog, anxiety, depression, musculoskeletal pain, fatigue, migraines and more.

Results: Patient age ranged from 18 to 65 years. The prevalence of common symptoms was as follows: migraines, 69%; brain fog, 76%; anxiety attacks, 58%; excess sweating, 64%; hip pain, 73%; diarrhea, 62%; constipation, 76%; and abdominal bloating, 82%. After treatment, most symptom scores improved by more than 50%; exceptions were excessive sweating (41% improvement) and bloating (47% improvement). Prevalence of individual symptoms that bundle into POTS ranged from 29% to 76%, where symptom improvement ranged from 23% to 59% after treatment. Overlapping individual symptoms characteristic of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) were present in 64% to 82% of patients and all improved by 49% to 63% after treatment.

Conclusions: Pelvic venous flow abnormality is linked causally to a spectrum of interrelated symptoms, of which many can be bundled into named syndromes of unknown cause. With catheter- based treatment of pelvic venous pooling, nonpelvic symptom and syndrome scores improved.

Source: Smith SJ, Smith BH, Sichlau MJ, Chen B, Knight D, Rowe PC. Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment. Phlebology. 2024 Aug 10:2683555241273109. doi: 10.1177/02683555241273109. Epub ahead of print. PMID: 39126670.  https://pubmed.ncbi.nlm.nih.gov/39126670/

‘The world was going through what we go through everyday’: The experiences of women with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) living with their partners during the COVID-19 lockdown in the United Kingdom

Abstract:

Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term debilitating illness characterised by profound and persistent fatigue (JAMA: The Journal of the American Medical Association, 313, 2015, 1101). The current study aims to explore the experiences of women with ME/CFS living with their partners during the COVID-19 pandemic in the United Kingdom.

Design: The study adopted a qualitative design comprising semi-structured interviews with participants. Interviews were analysed using thematic analysis (TA).

Methods: Participants were women with ME/CFS (n = 21) recruited through ME/CFS support groups in the United Kingdom. All participants were in romantic relationships and lived with their partners.

Results: Data were organised into three themes: (1) lockdown disrupting routine, (2) reducing difference and (3) fear of getting COVID-19. People with ME/CFS found that lockdown disrupted their well-established routines. Although routines were disrupted by partners and increased working-from-home practices, participants found having partners at home helpful. People with ME/CFS believed that the changes induced by the pandemic reduced the differences between themselves and the outside world which, prior to lockdown, had felt prominent. They were fearful of getting COVID-19 as they believed this would make their ME/CFS worse. This meant that for people with ME/CFS, the lifting of the lockdown restrictions was an anxiety-provoking time, hence impacting symptoms. People with ME/CFS continued to adhere to government guidelines after national restrictions were eased.

Conclusions: This study outlines the experiences of women with ME/CFS during COVID-19, alongside the long-term impact this has had due to the changes that the pandemic imposed. These findings may have implications for those with long COVID.

Source: Sehmbi T, Wearden A, Peters S, Dienes K. ‘The world was going through what we go through everyday’: The experiences of women with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) living with their partners during the COVID-19 lockdown in the United Kingdom. Br J Health Psychol. 2024 Mar 6. doi: 10.1111/bjhp.12717. Epub ahead of print. PMID: 38448223. https://bpspsychub.onlinelibrary.wiley.com/doi/10.1111/bjhp.12717 (Full text)

The impact of “long COVID” on menstruation in Chinese female college students and the intervention of acupuncture

Abstract:

This study aimed to explore the potential application value of acupuncture in alleviating the impact of long COVID on women’s menstrual cycles, by investigating the occurrence of long COVID among female college students, its effects on menstruation, and the intervention of acupuncture. This cross-sectional study surveyed female college students with a history of coronavirus disease 2019 (COVID-19) before April 10, 2023.

A questionnaire was used to analyze demographic characteristics, post-COVID sequelaes, duration of symptoms, and treatments received during that period. Among the 731 participants enrolled in the survey, 468 were female undergraduate students who met the analysis criteria. Among them, 85 individuals fit the definition of “Long COVID” (18.16%).

Within the group of patients with long COVID, 69 individuals experienced changes in their overall menstrual patterns compared to the 6 months prior to contracting the novel coronavirus (81.18%). Additionally, 17 individuals opted for acupuncture treatment following the onset of COVID-19 (20.00%), which resulted in less impact on their menstrual cycle (41.18% vs 64.71% without receiving acupuncture, OR = 2.62), menstrual period duration (41.18% vs 64.71%, OR = 2.62), menstrual flow (47.06% vs 69.18%, OR = 2.52), and the color of menstrual blood (41.18% vs 63.24%, OR = 2.46) among these patients. Long COVID had a certain impact on menstruation.

Acupuncture potentially alleviates the clinical symptoms of long COVID and reduces its impact on women’s menstrual cycle, thus having potential therapeutic value in the treatment of long COVID.

Source: Dong J, Ni J, Zhang Z, Yan H, Xu J, Zhao J. The impact of “long COVID” on menstruation in Chinese female college students and the intervention of acupuncture. Medicine (Baltimore). 2024 Feb 9;103(6):e36818. doi: 10.1097/MD.0000000000036818. PMID: 38335408; PMCID: PMC10860984. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860984/ (Full text)

High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study

Abstract:

The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections.

The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection.

In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC.

In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.

Source: Villa A, Milito C, Deiana CM, Gambier RF, Punziano A, Buso H, Bez P, Lagnese G, Garzi G, Costanzo G, Giannuzzi G, Pagnozzi C, Dalm VASH, Spadaro G, Rattazzi M, Cinetto F, Firinu D. High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study. J Clin Immunol. 2024 Feb 6;44(2):59. doi: 10.1007/s10875-024-01656-2. PMID: 38319477; PMCID: PMC10847195. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847195/ (Full text)

Association of vaccine status, reinfections, and risk factors with Long COVID syndrome

Abstract:

The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to determine the prevalence of Long COVID syndrome within a population of Northeastern Mexico, correlating it with patients’ comorbidities, number of COVID-19 reinfection, and vaccination status. Employing an observational cross-sectional approach, we administered a comprehensive questionnaire covering medical history, demographics, vaccination status, COVID-related symptoms, and treatment.

Our participant cohort included 807 patients, with an average age of 41.5 (SD 13.6) years, and women accounting 59.3% of the cohort. The follow-up was 488 (IQR 456) days. One hundred sixty-eight subjects (20.9%) met Long COVID criteria. Long COVID-19 was more prevalent when subjects had reinfections (p = 0.02) and less frequent when they had a complete vaccination scheme (p = 0.05).

Through logistic regression, we found that male gender (OR 0.5, p ≤ 0.001), blood types of AB- (OR 0.48, p = 0.003) and O- (OR 0.27, p ≤ 0.001) in comparison with A+ and two doses of vaccines (OR 0.5, p = 006) to be protective factors against Long COVID; while higher BMI (OR 1.04, p = 0.005) was a risk factor.

We saw that the prevalence of Long COVID was different within vaccinated patients and specific blood types, while being female and a higher BMI were associated with an increased risk of having long-COVID.

Source: Romero-Ibarguengoitia ME, Rodríguez-Torres JF, Garza-Silva A, Rivera-Cavazos A, Morales-Rodriguez DP, Hurtado-Cabrera M, Kalife-Assad R, Villarreal-Parra D, Loose-Esparza A, Gutiérrez-Arias JJ, Mata-Porras YG, Ojeda-Salazar DA, Sanz-Sánchez MA, González-Cantú A, Azzolini E, Rescigno M. Association of vaccine status, reinfections, and risk factors with Long COVID syndrome. Sci Rep. 2024 Feb 2;14(1):2817. doi: 10.1038/s41598-024-52925-4. PMID: 38307886; PMCID: PMC10837423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10837423/ (Full text)

Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection

Abstract:

Many patients surviving SARS-CoV-2 infection suffer from long-term symptoms (long COVID or post COVID) such as shortness of breath, fatigue, loss of taste or smell and cognitive deterioration. However, few data are available concerning blood cell counts and haematological parameters during the post-COVID period.

We analysed haematological data from 83 patients previously admitted to the internal medicine unit of our institution because of symptomatic SARS-CoV-2 infection; all data were obtained within 1-12 months from disease onset. A control group of 70 apparently healthy, age- and sex-matched COVID-19 negative individuals was assessed for comparison. Blood cell counts improved in the post-COVID period, but 81% of patients had persistent abnormalities, compared with 50% in the control group, p < 0.001.

Most common haematological findings included anaemia (40%), reduced lymphocyte (43%) or eosinophil counts (38%) and low IgM memory B cells and correlated with advanced age, number of chronic comorbidities, female gender, altered renal function, reduced baseline Hb and procalcitonin concentrations and increased RDW. Data on lymphocytes and IgM memory B cells show that impaired immune responses may persist for up to one year in the post-COVID period, possibly contributing to long-term symptoms, especially in female patients.

Source: Bergamaschi G, Barteselli C, Calabretta F, Lenti MV, Merli S, Rossi CM, Di Sabatino A. Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection. Intern Emerg Med. 2024 Jan;19(1):125-133. doi: 10.1007/s11739-023-03459-6. Epub 2023 Nov 24. PMID: 38001354. https://pubmed.ncbi.nlm.nih.gov/38001354/

Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic

Abstract:

Purpose: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated.

Methods: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances.

Results: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints.

Conclusion: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.

Source: Sakurada Y, Matsuda Y, Motohashi K, Hasegawa T, Otsuka Y, Nakano Y, Tokumasu K, Yamamoto K, Sunada N, Honda H, Hagiya H, Ueda K, Otsuka F. Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic. J Psychosom Obstet Gynaecol. 2024 Dec;45(1):2305899. doi: 10.1080/0167482X.2024.2305899. Epub 2024 Jan 25. PMID: 38270210. https://www.tandfonline.com/doi/full/10.1080/0167482X.2024.2305899 (Full text)