New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition

Abstract:

Fibromyalgia can be defined as a chronic pain condition, affecting the musculoskeletal system, etiology and pathophysiology of which is sufficiently understudied. Despite the fact that many authors consider this entity to be a manifestation of central sensitization, and not an autoimmune disease, the high prevalence of fibromyalgia in patients with post-COVID-19 conditions requires taking a fresh look at the causes of the disease development.

During the patient examination, the authors identified a combination of symptoms that occurs so often, that they can be carefully described as a clinical pattern. These manifestations include young age, female gender, joint hypermobility, the onset of pain after COVID-19, physical traumatization of one particular tendon and the development of the fibromyalgia pain syndrome during the next several weeks. As well as an increase in the titer of antinuclear antibodies and some other systemic inflammation factors. It can be assumed with great caution that local damage to the connective tissue in patients with joint hypermobility, having COVID-19 as a trigger factor can lead to the development of fibromyalgia syndrome. This article presents three clinical cases that illustrated this hypothesis.

Source: Gavrilova N, Soprun L, Lukashenko M, Ryabkova V, Fedotkina TV, Churilov LP, Shoenfeld Y. New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition. Pathophysiology. 2022 Jan 19;29(1):24-29. doi: 10.3390/pathophysiology29010003. PMID: 35366287. https://www.mdpi.com/1873-149X/29/1/3/htm (Full text)

A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression

Abstract:

Background: Functional somatic disorders (FSD) feature medical symptoms of unclear etiology. Attempts to clarify their origin have been hampered by a lack of rigorous research designs. We sought to clarify the etiology of the FSD by examining the genetic risk patterns for FSD and other related disorders.

Methods: This study was performed in 5 829 186 individuals from Swedish national registers. We quantified familial genetic risk for FSD, internalizing disorders, and somatic disorders in cases of chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), using a novel method based on aggregate risk in first to fifth degree relatives, adjusting for cohabitation. We compared these profiles with those of a prototypic internalizing psychiatric – major depression (MD) – and a somatic/autoimmune disorder: rheumatoid arthritis (RA).

Results: Patients with FM carry substantial genetic risks not only for FM, but also for pain syndromes and internalizing, autoimmune and sleep disorders. The genetic risk profiles for IBS and CFS are also widely distributed although with lower average risks. By contrast, genetic risk profiles of MD and RA are much more restricted to related conditions.

Conclusion: Patients with FM have a relatively unique family genetic risk score profile with elevated genetic risk across a range of disorders that differs markedly from the profiles of a classic autoimmune disorder (RA) and internalizing disorder (MD). A similar less marked pattern of genetic risks was seen for IBS and CFS. FSD arise from a distinctive pattern of genetic liability for a diversity of psychiatric, autoimmune, pain, sleep, and functional somatic disorders.

Source: Kendler KS, Rosmalen JGM, Ohlsson H, Sundquist J, Sundquist K. A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression. Psychol Med. 2022 Mar 31:1-8. doi: 10.1017/S0033291722000526. Epub ahead of print. PMID: 35354508.

Number of initial symptoms is more related to long COVID-19 than acute severity of infection: a prospective cohort of hospitalized patients

Abstract:

Objectives: Post–COVID-19 symptoms experienced by many survivors have a further devastating effect. This study aimed to analyze the risk factors associated with long COVID-19 in a prospective cohort of hospitalized patients including those requiring intensive care unit (ICU) transfer, taking into account objective measures of COVID-19 severity.

Methods: Hospitalized patients with confirmed COVID-19 were enrolled. A structured follow-up visit was performed 4 months after hospital admission. Multivariable adjusted regression models were used to analyse the association between parameters at the acute phase and persistent symptoms.

Results: A follow-up visit was performed in 316 patients including 115 (36.4%) discharged from the ICU. Mean age was 64.1 years, and 201 patients (58.3%) were men. Female sex (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.17-3.22; P =.01), hypertension (OR, 2.01; 95% CI, 1.22-3.31; P <.01), and the number of initial symptoms (NIS) (OR, 1.35; 95% CI, 1.17-1.54; P <.001) were significantly associated with long COVID-19. Number of persistent symptoms was significantly associated with NIS (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.11-1.22; P <.001), female sex (aIRR, 1.56; 95% CI 1.29-1.87; P <.001), hypertension (aIRR, 1.23; 95% CI, 1.02-1.50; P =.03), and length of stay in hospital (aIRR, 1.01; 95% CI, 1.005-1.017; P <.001).

Conclusion: Our study suggested that female sex, hypertension, and NIS had a significant impact on persistent symptoms in hospitalized patients in contrast to severity of acute COVID-19 infection.

Source: Adrien CSK, Alexandre C, Marie M, Cédric J, Schmit JL, Jean-Philippe L, Claire A. Number of initial symptoms is more related to long COVID-19 than acute severity of infection: a prospective cohort of hospitalized patients. Int J Infect Dis. 2022 Mar 4;118:220–3. doi: 10.1016/j.ijid.2022.03.006. Epub ahead of print. PMID: 35257903; PMCID: PMC8896858. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896858/ (Full text)

Toward Unbiased Evaluation of Postacute Sequelae of SARS-CoV-2 Infection: Challenges and Solutions for the Long Haul Ahead

Abstract:

The authors argue that postacute SARS-CoV-2 syndrome presents unique challenges in determining risk factors, natural history, and proper management. They call for strategies and actions that are based on rigorous, high-quality evidence.

Source: Wisk LE, Nichol G, Elmore JG. Toward Unbiased Evaluation of Postacute Sequelae of SARS-CoV-2 Infection: Challenges and Solutions for the Long Haul Ahead. Ann Intern Med. 2022 Mar 8:M21-4664. doi: 10.7326/M21-4664. Epub ahead of print. PMID: 35254883; PMCID: PMC8906529. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906529/ (Full text)

Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study

Abstract:

Objective: To characterize the risk of persistent and new clinical sequelae in adults aged ≥65 years after the acute phase of SARS-CoV-2 infection.

Design: Retrospective cohort study.

Setting: UnitedHealth Group Clinical Research Database: deidentified administrative claims and outpatient laboratory test results.

Participants: Individuals aged ≥65 years who were continuously enrolled in a Medicare Advantage plan with coverage of prescription drugs from January 2019 to the date of diagnosis of SARS-CoV-2 infection, matched by propensity score to three comparison groups that did not have covid-19: 2020 comparison group (n=87 337), historical 2019 comparison group (n=88 070), and historical comparison group with viral lower respiratory tract illness (n=73 490).

Main outcome measures: The presence of persistent and new sequelae at 21 or more days after a diagnosis of covid-19 was determined with ICD-10 (international classification of diseases, 10th revision) codes. Excess risk for sequelae caused by infection with SARS-CoV-2 was estimated for the 120 days after the acute phase of the illness with risk difference and hazard ratios, calculated with 95% Bonferroni corrected confidence intervals. The incidence of sequelae after the acute infection was analyzed by age, race, sex, and whether patients were admitted to hospital for covid-19.

Results: Among individuals who were diagnosed with SARS-CoV-2, 32% (27 698 of 87 337) sought medical attention in the post-acute period for one or more new or persistent clinical sequelae, which was 11% higher than the 2020 comparison group. Respiratory failure (risk difference 7.55, 95% confidence interval 7.18 to 8.01), fatigue (5.66, 5.03 to 6.27), hypertension (4.43, 2.27 to 6.37), memory difficulties (2.63, 2.23 to 3.13), kidney injury (2.59, 2.03 to 3.12), mental health diagnoses (2.50, 2.04 to 3.04), hypercoagulability 1.47 (1.2 to 1.73), and cardiac rhythm disorders (2.19, 1.76 to 2.57) had the greatest risk differences compared with the 2020 comparison group, with similar findings to the 2019 comparison group. Compared with the group with viral lower respiratory tract illness, however, only respiratory failure, dementia, and post-viral fatigue had increased risk differences of 2.39 (95% confidence interval 1.79 to 2.94), 0.71 (0.3 to 1.08), and 0.18 (0.11 to 0.26) per 100 patients, respectively. Individuals with severe covid-19 disease requiring admission to hospital had a markedly increased risk for most but not all clinical sequelae.

Conclusions: The results confirm an excess risk for persistent and new sequelae in adults aged ≥65 years after acute infection with SARS-CoV-2. Other than respiratory failure, dementia, and post-viral fatigue, the sequelae resembled those of viral lower respiratory tract illness in older adults. These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus.

Source: Cohen K, Ren S, Heath K, Dasmariñas MC, Jubilo KG, Guo Y, Lipsitch M, Daugherty SE. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ. 2022 Feb 9;376:e068414. doi: 10.1136/bmj-2021-068414. PMID: 35140117; PMCID: PMC8828141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828141/ (Full text)

How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study

Abstract:

Background: Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan.

Methods: 7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000-2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011.

Results: The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person-years among the non-Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03-1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02-1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86-3.38).

Conclusions: The data from this population-based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.

Source: Yang TY, Lin CL, Yao WC, Lio CF, Chiang WP, Lin K, Kuo CF, Tsai SY. How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study. J Transl Med. 2022 Feb 21;20(1):99. doi: 10.1186/s12967-022-03301-1. PMID: 35189895. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03301-1 (Full text)

Determinants of Persistence of Symptoms and Impact on Physical and Mental Wellbeing in Long COVID: A Prospective Cohort Study

Abstract:

Background: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analysed a prospective cohort of COVID-19 patients.

Methods: Patients were followed for 9 months after COVID-19 onset. Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed.

Results: 465 patients (54% males, 51% hospitalised) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalisation and ICU stay vs. non-hospitalised status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress.

Conclusions: Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing. This study contributes to identify the target populations and Long COVID consequences for planning long-term recovery interventions.

Source: Righi E, Mirandola M, Mazzaferri F, Dossi G, Razzaboni E, Zaffagnini A, Ivaldi F, Visentin A, Lambertenghi L, Arena C, Micheletto C, Gibellini D, Tacconelli E. Determinants of Persistence of Symptoms and Impact on Physical and Mental Wellbeing in Long COVID: A Prospective Cohort Study. J Infect. 2022 Feb 9:S0163-4453(22)00065-2. doi: 10.1016/j.jinf.2022.02.003. Epub ahead of print. PMID: 35150765; PMCID: PMC8828388. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828388/ (Full text)

Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review

Abstract:

Background: Long COVID-19 may affect patients after hospital discharge.

Aims: This study aims to describe the burden of the long-term persistence of clinical symptoms in COVID-19 patients.

Methods: We conducted a systematic review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The PubMed and Google Scholar databases were searched for studies that included information on the prevalence of somatic clinical symptoms lasting at least 4 weeks after the onset of a PCR- or serology-confirmed diagnosis of COVID-19. The prevalence of persisting clinical symptoms was assessed and risk factors were described when investigated. Psychological symptoms and cognitive disorders were not evaluated in this study.

Results: Thirty-seven articles met the inclusion criteria. Eighteen studies involved in-patients only with a duration of follow-up of either less than 12 weeks, 12 weeks to 6 months, or more. In these studies, fatigue (16-64%), dyspnea (15-61%), cough (2-59%), arthralgia (8-55%), and thoracic pain (5-62%) were the most frequent persisting symptoms. In nineteen studies conducted in a majority of out-patients, the persistence of these symptoms was lower and 3% to 74% of patients reported prolonged smell and taste disorders. The main risk factors for persisting symptoms were being female, older, having comorbidities and severity at the acute phase of the disease.

Conclusion: COVID-19 patients should have access to dedicated multidisciplinary healthcare allowing a holistic approach. Effective outpatient care for patients with long-COVID-19 requires coordination across multiple sub-specialties, which can be proposed in specialized post-COVID units.

Source: Nguyen NN, Hoang VT, Dao TL, Dudouet P, Eldin C, Gautret P. Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review. Eur J Clin Microbiol Infect Dis. 2022 Feb 10:1–31. doi: 10.1007/s10096-022-04417-4. Epub ahead of print. PMID: 35142947; PMCID: PMC8830952. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830952/ (Full text)

Covid-19: Antibody “signature” could predict risk of long covid

Researchers have identified an immunoglobulin “signature” that could be used to predict which patients are most at risk of developing post-acute covid syndrome (PACS), otherwise known as long covid.

In a multicentre prospective study, 175 patients with covid-19 and 40 healthy control group participants were followed for up to a year. More than half of the patients with covid reported long covid symptoms lasting longer than a month. Those who developed long covid were found to have lower levels of IgM and IgG3 antibodies than those who quickly recovered, found the research, published in Nature Communications.1 A history of asthma was also highly associated with PACS, the study found.

The researchers combined data on immunoglobulin concentrations with a patient’s age, history of asthma, and five symptoms during the primary infection to develop a PACS score that could predict the risk of developing long term illness. The PACS score was then validated in an independent group of 395 people with covid-19.

The researchers, from the University of Zurich, said that the score might be especially helpful in hospital settings for early identification of those patients at a very high risk of developing PACS. It could also allow the study of targeted preventive treatments such as inhaled corticosteroids or intravenous immunoglobulin treatments.

The researchers said more research was still needed but that a PACS score or long covid risk calculator would be available soon at pacs-score.com.

The study’s limitations included that participants were infected between April 2020 and August 2021, before the omicron variant took hold. And the study didn’t take into account participants’ vaccination status.

Claire Steves, a senior clinical lecturer at King’s College London, welcomed the research, saying, “With cases high still, more people are at risk of developing long term symptoms. We urgently need to scale up research on how to prevent this happening. Tools such as these predictive models could be used to identify people at higher risk for enrolment into research trials for therapeutics.”

But she added, “This is a small study that was undertaken in a selected population, and so in particular the immune findings do need to be replicated elsewhere.”

Amitava Banerjee, professor of clinical data science and honorary consultant cardiologist at University College London, commented, “There are three implications from this research. First, the immunoglobulin signature points more clearly towards the mechanism of disease, although replication of the results in different, larger cohorts is needed. Second, this raises the possibility of being able to predict the risk of long covid in individuals post-initial infection. Third, further research is required to understand whether similar risk factor profiles can be used to predict the prognosis or speed of recovery.”

Read the rest of this article HERE.

Source: Jacqui Wise. Covid-19: Antibody “signature” could predict risk of long covid. BMJ 2022376 doi: https://doi.org/10.1136/bmj.o245 (Published 28 January 2022)

Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort

Abstract:

Background: The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed.

Methods: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results: Of 3’334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions: Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Source: Strahm C, Seneghini M, Güsewell S, Egger T, Leal O, Brucher A, Lemmenmeier E, Meier Kleeb D, Möller JC, Rieder P, Ruetti M, Rutz R, Schmid HR, Stocker R, Vuichard-Gysin D, Wiggli B, Besold U, Kuster SP, McGeer A, Risch L, Friedl A, Schlegel M, Schmid D, Vernazza P, Kahlert CR, Kohler P. Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort. Clin Infect Dis. 2022 Jan 28:ciac054. doi: 10.1093/cid/ciac054. Epub ahead of print. PMID: 35090015. https://pubmed.ncbi.nlm.nih.gov/35090015/  (Full text available as PDF file)