Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla.

Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.”

In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.” Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.

Source: Thapaliya K, Marshall-Gradisnik S, Barth M, Eaton-Fitch N, Barnden L. Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients. Frontiers in Neuroscience, 2023 March 2; 17:1125208. https://www.frontiersin.org/articles/10.3389/fnins.2023.1125208/full (Full text)

Two-year follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study

Summary:

Background: Few studies have reported the long-term health effects of COVID-19. The regional population-based Linköping COVID-19 study (LinCoS) included all patients hospitalised due to COVID-19 during the first pandemic wave. Four months post-discharge, over 40% (185/433) experienced persisting symptoms and activity/participation limitations, indicating post-COVID-19 condition (PCC). The present follow-up study aimed to determine the long-term recovery among these patients 24 months post-admission.

Methods: This prospective cohort study included all patients from LinCoS with PCC at four months post-discharge. We repeated the same structured interview at a 24-month follow-up to identify persisting symptoms and their impact on daily life. Intercurrent health issues were identified by reviewing medical records.

Findings: Of 185 patients with PCC at 4 months post-discharge, 181 were alive at the 24-month assessment and 165 agreed to participate. Of those, 21% (35/165) had been readmitted to hospital for various causes in the interim period. The majority of patients (139/165, 84%) reported persisting problems affecting everyday life at 24 months. Significant improvements were seen in the prevalence and magnitude of some symptoms/limitations compared with four months post-discharge. Cognitive, sensorimotor, and fatigue symptoms were the most common persisting symptoms at 24 months. No clear difference was evident between individuals treated in the intensive care unit (ICU) and non-ICU-treated individuals. Approximately half of those who were on sick leave related to PCC at four months after infection were on sick leave at 24 months.

Interpretation: This is one of the first studies to report 2-year outcomes in patients with PCC following COVID-19 hospitalisation. Despite some improvements over time, we found a high prevalence of persisting symptoms and a need for long-term follow-up and rehabilitation post COVID-19 infection.

Source: Carl Wahlgren et al. Two-year follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study. The Lancet Regional Health – Europe. DOI:https://doi.org/10.1016/j.lanepe.2023.100595 https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00013-3/fulltext (Full text)

The Very Long COVID: Persistence of Symptoms after 12–18 Months from the Onset of Infection and Hospitalization

Abstract:

According to the World Health Organization’s definition, long COVID is the persistence or development of new symptoms 3 months after the initial infection. Various conditions have been explored in studies with up to one-year follow-up but very few looked further. This prospective cohort study addresses the presence of a wide spectrum of symptoms in 121 patients hospitalized during the acute phase of COVID-19 infection, and the association between factors related to the acute phase of the disease and the presence of residual symptoms after one year or longer from hospitalization.
The main results are as follows: (i) post-COVID symptoms persist in up to 60% of the patient population at a mean follow-up of 17 months; (ii) the most frequent symptoms are fatigue and dyspnea, but neuropsychological disturbances persist in about 30% of the patients (iii) when corrected for the duration of follow-up with a freedom-from-event analysis; only complete (2 doses) vaccination at the time of hospital admission remained independently associated with persistence of the major physical symptoms, while vaccination and previous neuropsychological symptoms remained independently associated with persistence of major neuropsychological symptoms.
Source: Ranucci M, Baryshnikova E, Anguissola M, Pugliese S, Ranucci L, Falco M, Menicanti L. The Very Long COVID: Persistence of Symptoms after 12–18 Months from the Onset of Infection and Hospitalization. Journal of Clinical Medicine. 2023; 12(5):1915. https://doi.org/10.3390/jcm12051915 https://www.mdpi.com/2077-0383/12/5/1915 (Full text)

The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID – results from the prospective population-based COVI-GAPP study

Abstract:

Background During and after mild (no hospitalization) or moderate (hospitalization without ICU) SARS-CoV-2 infections, a wide range of symptoms, including neurological disorders have been reported. It is, however, unknown if these neurological symptoms are associated with brain injury and whether brain injury and related symptoms also emerge in patients suffering from Long-COVID. Neuronal biomarkers such as serum neurofilament light chain and glial fibrillary acidic protein can be used to elucidate neuro-axonal and astroglial injuries. We therefore investigated whether these biomarkers are associated with the COVID-19 infection status (mild-to-moderate), the associated symptoms and Long-COVID.

Methods From 146 individuals of the general population with a post-acute, mild-to-moderate SARS-CoV-2 infection, serum neurofilament light chain (sNfL; marker of intra-axonal neuronal injury) and serum glial fibrillary acidic protein (sGFAP; marker of astrocytic activation/injury) were measured. Samples were taken before, during and after (five and ten months) a SARS-CoV-2 infection. Individual symptoms and Long-COVID status were assessed using questionnaires.

Results Neurological symptoms were described for individuals after a mild and moderate COVID-19 infection, however, serum markers of brain injury (sNfL/sGFAP) did not change after an infection (sNfL: P = 0.74; sGFAP: P = 0.24) and were not associated with headache (P = 0.51), fatigue (P = 0.93), anosmia (P = 0.77) and ageusia (P = 0.47). In participants with Long-COVID, sGFAP (P = 0.038), but not sNfL (P = 0.58) significantly increased but was not associated with neurological symptoms.

Conclusion Neurological symptoms in individuals after a mild-to-moderate SARS-CoV-2 infection with and without Long-COVID were not associated with brain injury, although there was some astroglial injury observed in Long-COVID patients.

Source: Julia TelserKirsten GrossmannOrnella C WeideliDorothea HillmannStefanie AeschbacherNiklas WohlwendLaura VelezJens KuhleAleksandra MaleskaPascal BenkertCorina RischDavid ConenMartin RischLorenz Risch. The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID – results from the prospective population-based COVI-GAPP study.

Left atrial longitudinal strain analysis in long Covid-19 syndrome

Abstract:

It is known that during the active course of Coronavirus disease 2019 (COVID-19), myocardial injury has an established pathological base, while its myocardial injury post-recovery is still obscured.

The aim of this study was to evaluate the longitudinal left atrial strain (LAS) using speckle tracking echocardiography (STE) in COVID-19-recovered patients who are previously healthy without confounder comorbidities to detect the potential cardiac dysfunction. 200 patients were prospectively included and examined 4?12 weeks after recovery from COVID-19 infection. 137 participants with comorbidities or previous history of cardiopulmonary disease were excluded from the analysis. A total of 63 patients who fulfilled our inclusion criteria were recruited into two groups according to the presence or absence of persistent dyspnoea and exercise intolerance. Clinical, laboratory & comprehensive echocardiographic examinations were done for all.

We observed that 31.7% of the previously healthy individuals developed dyspnoea & exercise intolerance post-COVID-19 infection. There were significantly impaired LAS parameters in the symptomatic group (LA reservoir, contraction & conduit strain, 22.7%, -6.6% & -16.1% versus 40%, -12%, and ? 27% in the asymptomatic group with P < 0.000).

Only LA reservoir strain and LA stiffness can independently predict the development of dyspnoea & exercise intolerance post-COVID-19 at cut-off values of 30% & 24.5% respectively with a sensitivity of 90% and a specificity of 91%, P < 0.001. These impaired LAS parameters could explain the developed symptoms post-COVID-19 recovery, even before disturbed conventional diastolic echocardiographic parameters. LAS parameters are significantly associated with the developed exertional dyspnoea & exercise intolerance post-COVID-19. LA reservoir strain & LA stiffness could provide a simple, easily available tool that points to early LV diastolic dysfunction and may direct the therapy in this subset of the population.

Source: ZeinElabdeen SG, Sherif A, Kandil NT, Altabib AMO, Abdelrashid MA. Left atrial longitudinal strain analysis in long Covid-19 syndrome. Int J Cardiovasc Imaging. 2023 Feb 14:1–6. doi: 10.1007/s10554-023-02801-5. Epub ahead of print. PMID: 36786877; PMCID: PMC9927057. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927057/ (Full text)

An Exploratory Factor Analysis of Long Covid

Abstract:
An exploratory factor analysis (EFA) can provide a window into the latent dimensions of a disease, such as Long COVID.
Discovering the latent factors of Long COVID enables researchers and clinicians to better conceptualize, study and treat
this disease.
In this study, participants were recruited from social media sites dedicated to COVID and Long COVID. Among the 480 participants, those who completed at least 90% of the survey, reported symptoms for two or more months since COVID-19 symptom onset, and had not been hospitalized for COVID were used in the EFA. The mean duration since initial symptom onset was 74.0 (37.3) weeks.
A new questionnaire called The DePaul Symptom Questionnaire-COVID was used to assess self-reports of the frequency and severity of 38 Long COVID symptoms experienced over the most recent month. The most burdensome symptoms were “Symptoms that get worse after physical or mental activities (also known as Post-Exertional Malaise),” “Fatigue/extreme tiredness,” “Difficulty thinking and/or concentrating,” “Sleep problems,” and “Muscle aches.” The EFA resulted in a three-factor model with factors labeled General, PEM/Fatigue/Cognitive Dysfunction, and Psychological, consisting of 16, 6, and 3 items respectively (25 items in total).
The reliability of the items in the EFA was .90 using a split-half reliability test. Finally, participant self-reported level of
functional impairment was analyzed across the three EFA factors. Interpretations and applications to research and
practice are provided.
Source: Joseph A. Dorri1 and Leonard A. Jason. An exploratory factor analysis of long covid. Central Asian Journal of Medical Hypotheses and Ethics. 2/14/23 https://www.researchgate.net/publication/368502945_AN_EXPLORATORY_FACTOR_ANALYSIS_OF_LONG_COVID (Full text)

The Role of Interferons in Long Covid Infection

Abstract:

Although the new generation of vaccines and anti-COVID-19 treatment regimens facilitated the management of acute COVID-19 infections, concerns about post-COVID-19 syndrome or Long Covid are rising. This issue can increase the incidence and morbidity of diseases such as diabetes, and cardiovascular, and lung infections, especially among patients suffering from neurodegenerative disease, cardiac arrhythmias, and ischemia.

There are numerous risk factors that cause COVID-19 patients to experience post-COVID-19 syndrome. Three potential causes attributed to this disorder include immune dysregulation, viral persistence, and autoimmunity. Interferons (IFNs) are crucial in all aspects of post-COVID-19 syndrome etiology.

In this review, we discuss the critical and double-edged role of IFNs in post-COVID-19 syndrome and how innovative biomedical approaches that target IFNs can reduce the occurrence of Long Covid infection.

Source: Karbalaeimahdi M, Farajnia S, Bargahi N, Ghadiri-Moghaddam F, Rasouli Jazi HR, Bakhtiari N, Ghasemali S, Zarghami N. The Role of Interferons in Long Covid Infection. J Interferon Cytokine Res. 2023 Feb;43(2):65-76. doi: 10.1089/jir.2022.0193. PMID: 36795973. https://pubmed.ncbi.nlm.nih.gov/36795973/

Association of Post-COVID-19 Condition Symptoms and Employment Status

Abstract:

Importance: Little is known about the functional correlates of post-COVID-19 condition (PCC), also known as long COVID, particularly the relevance of neurocognitive symptoms.

Objective: To characterize prevalence of unemployment among individuals who did, or did not, develop PCC after acute infection.

Design, setting, and participants: This survey study used data from 8 waves of a 50-state US nonprobability internet population-based survey of respondents aged 18 to 69 years conducted between February 2021 and July 2022.

Main outcomes and measures: The primary outcomes were self-reported current employment status and the presence of PCC, defined as report of continued symptoms at least 2 months beyond initial month of symptoms confirmed by a positive COVID-19 test.

Results: The cohort included 15 308 survey respondents with test-confirmed COVID-19 at least 2 months prior, of whom 2236 (14.6%) reported PCC symptoms, including 1027 of 2236 (45.9%) reporting either brain fog or impaired memory. The mean (SD) age was 38.8 (13.5) years; 9679 respondents (63.2%) identified as women and 10 720 (70.0%) were White. Overall, 1418 of 15 308 respondents (9.3%) reported being unemployed, including 276 of 2236 (12.3%) of those with PCC and 1142 of 13 071 (8.7%) of those without PCC; 8229 respondents (53.8%) worked full-time, including 1017 (45.5%) of those with PCC and 7212 (55.2%) without PCC. In survey-weighted regression models excluding retired respondents, the presence of PCC was associated with a lower likelihood of working full-time (odds ratio [OR], 0.71 [95% CI, 0.63-0.80]; adjusted OR, 0.84 [95% CI, 0.74-0.96]) and with a higher likelihood of being unemployed (OR, 1.45 [95% CI, 1.22-1.73]; adjusted OR, 1.23 [95% CI, 1.02-1.48]). The presence of any cognitive symptom was associated with lower likelihood of working full time (OR, 0.70 [95% CI, 0.56-0.88]; adjusted OR, 0.75 [95% CI, 0.59-0.84]).

Conclusions and relevance: PCC was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. The presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to treat and manage PCC symptoms.

Source: Perlis RH, Lunz Trujillo K, Safarpour A, Santillana M, Ognyanova K, Druckman J, Lazer D. Association of Post-COVID-19 Condition Symptoms and Employment Status. JAMA Netw Open. 2023 Feb 1;6(2):e2256152. doi: 10.1001/jamanetworkopen.2022.56152. PMID: 36790806; PMCID: PMC9932847. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932847/(Full text)

Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study

Abstract:

Objective: The aim of this study was to investigate the epidemiology of post-COVID conditions beyond 12 months and identify factors associated with the persistence of each condition.

Study design: This was a cross-sectional questionnaire-based survey.

Methods: We conducted the survey among patients who had recovered from COVID-19 and visited our institute between February 2020 and November 2021. Demographic and clinical data and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the persistence of post-COVID conditions using multivariable linear regression analyses.

Results: Of 1148 surveyed patients, 502 completed the survey (response rate, 43.7%). Of these, 393 patients (86.4%) had mild disease in the acute phase. The proportion of participants with at least one symptom at 6, 12, 18, and 24 months after symptom onset or COVID-19 diagnosis was 32.3% (124/384), 30.5% (71/233), 25.8% (24/93), and 33.3% (2/6), respectively. The observed associations were as follows: fatigue persistence with moderate or severe COVID-19 (β = 0.53, 95% confidence interval [CI] = 0.06-0.99); shortness of breath with moderate or severe COVID-19 (β = 1.39, 95% CI = 0.91-1.87); cough with moderate or severe COVID-19 (β = 0.84, 95% CI = 0.40-1.29); dysosmia with being female (β = -0.57, 95% CI = -0.97 to -0.18) and absence of underlying medical conditions (β = -0.43, 95% CI = -0.82 to -0.05); hair loss with being female (β = -0.61, 95% CI = -1.00 to -0.22), absence of underlying medical conditions (β = -0.42, 95% CI = -0.80 to 0.04), and moderate or severe COVID-19 (β = 0.97, 95% CI = 0.41-1.54); depressed mood with younger age (β = -0.02, 95% CI = -0.04 to -0.004); and loss of concentration with being female (β = -0.51, 95% CI = -0.94 to -0.09).

Conclusions: More than one-fourth of patients after recovery from COVID-19, most of whom had had mild disease in the acute phase, had at least one symptom at 6, 12, 18, and 24 months after onset of COVID-19, indicating that not a few patients with COVID-19 suffer from long-term residual symptoms, even in mild cases.

Source: Morioka S, Tsuzuki S, Maruki T, Terada M, Miyazato Y, Kutsuna S, Saito S, Shimanishi Y, Takahashi K, Sanada M, Ashida S, Akashi M, Kuge C, Osanai Y, Tanaka K, Suzuki M, Hayakawa K, Ohmagari N. Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study. Public Health. 2023 Feb 13;216:39-44. doi: 10.1016/j.puhe.2023.01.008. Epub ahead of print. PMID: 36791649. https://www.sciencedirect.com/science/article/pii/S0033350623000173?via%3Dihub (Full text)

Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study

Abstract:

Symptoms of long COVID-19 syndrome (long COVID-19) are reported by 80% of convalescents up to several months after contracting the coronavirus-19 disease (COVID-19). The study aimed to assess the frequency and correlations of long COVID symptoms with sex, disease severity, time since the onset of the disease, and exercise capacity in a population of Polish convalescents hospitalized as a part of a rehabilitation program after COVID-19.

The retrospective analysis was carried out based on medical records concerning reported symptoms, comorbidities, exercise capacity, fatigue and dyspnea on Borg’s scale, arterial oxygen saturation (SpO2), spirometric parameters, chest X-rays/computed tomography scans, systolic pulmonary artery pressure, and left ventricular ejection fraction. The study involved 471 patients aged 63.83 ± 9.93 years who had been hospitalized 191.32 ± 75.69 days from the onset of COVID-19, of which 269 (57.1%) were women. The most common symptoms were fatigue (99.57%), dyspnea (99.36%), and myalgia (97.03%). Women reported more symptoms than men (p < 0.001) and rated their fatigue as more severe (p = 0.021). Patients with depressed moods reported more physical symptoms than others (p < 0.001).

Most long COVID symptoms, including dyspnea, fatigue, and depressive symptoms, were found with the same frequency in patients 12-24 weeks and >24 weeks after recovery (p = 0.874, p = 0.400, and p = 0.320, respectively), regardless of acute COVID-19 severity (p = 0.240, p = 0.826, and p = 0.108, respectively). Dyspnea severity correlated with forced vital capacity (FVC) (r = -0.153, p = 0.005), and forced expiratory volume in one second (FEV1) (r = -0.142, p = 0.008). Fatigue severity correlated with impaired FVC and FEV1 (both r = -0.162, p = 0.003). Fatigue and dyspnea inversely correlated with the distance in a six-minute walk test (r = -0.497, p < 0.001, and r = -0.327, p < 0.001).

In conclusion, in our cohort, long COVID symptoms are more common in women. Dyspnea/fatigue and depressive symptoms do not tend to subside after an average six-month recovery period. The intensity of perceived fatigue may be exaggerated by the coexistence of neuropsychiatric disorders. Increased fatigue and dyspnea correlate with impaired spirometric parameters and significantly affects convalescents’ exercise capacity.

Source: Paradowska-Nowakowska E, Łoboda D, Gołba KS, Sarecka-Hujar B. Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study. Life (Basel). 2023 Feb 11;13(2):508. doi: 10.3390/life13020508. PMID: 36836865; PMCID: PMC9961608. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961608/ (Full text)