Tag: long covid symptoms

Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors

Abstract:

Background: Severe clinical pictures and sequelae of COVID-19 disease are immune mediated and characterized by a ‘cytokine storm’. Skeletal muscle has emerged as a potent regulator of immune system function. The aim of the present study is to define the prevalence of sarcopenia among COVID-19 survivors and the negative impact of sarcopenia on the post-acute COVID-19 syndrome and its related risk factors.

Methods: A total of 541 subjects recovered from COVID-19 disease were enrolled in the Gemelli Against COVID-19 Post-Acute Care between April 2020 and February 2021. They underwent a multidisciplinary clinical evaluation and muscle strength and physical performance assessment.

Results: Mean age was 53.1 years (SD 15.2, range from 18 to 86 years), and 274 (51%) were women. The prevalence of sarcopenia was 19.5%, and it was higher in patients with a longer hospital stay and lower in patients who were more physically active and had higher levels of serum albumin. Patients with sarcopenia had a higher number of persistent symptoms than non-sarcopenic patients (3.8 ± 2.9 vs. 3.2 ± 2.8, respectively; P = 0.06), in particular fatigue, dyspnoea, and joint pain.

Conclusions: Sarcopenia identified according to the EWGSOP2 criteria is high in patients recovered from COVID-19 acute illness, particularly in those who had experienced the worst clinical picture reporting the persistence of fatigue and dyspnoea. Our data suggest that sarcopenia, through the persistence of inflammation, could be the biological substrate of long COVID-19 syndrome. Physical activity, especially if associated with adequate nutrition, seems to be an important protective factor.

Source: Martone AM, Tosato M, Ciciarello F, Galluzzo V, Zazzara MB, Pais C, Savera G, Calvani R, Marzetti E, Robles MC, Ramirez M, Landi F; Gemelli Against COVID-19 Post-Acute Care Team. Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors. J Cachexia Sarcopenia Muscle. 2022 Jun 14. doi: 10.1002/jcsm.12931. Epub ahead of print. PMID: 35698920. https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12931 (Full text)

Long-Term Symptoms of COVID-19: One-Year Follow-Up Study

Abstract:

Introduction: Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome.

Methods: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States).

Results: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%).

Conclusion: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals’ attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.

Source: Shivani F, Kumari N, Bai P, et al. (June 14, 2022) Long-Term Symptoms of COVID-19: One-Year Follow-Up Study. Cureus 14(6): e25937. doi:10.7759/cureus.25937 https://www.cureus.com/articles/91406-long-term-symptoms-of-covid-19-one-year-follow-up-study (Full text)

A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study

Abstract:

Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition.

To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19.

The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide.

Source: Munblit D, Nicholson T, Akrami A, Apfelbacher C, Chen J, De Groote W, Diaz JV, Gorst SL, Harman N, Kokorina A, Olliaro P, Parr C, Preller J, Schiess N, Schmitt J, Seylanova N, Simpson F, Tong A, Needham DM, Williamson PR; PC-COS project steering committee. A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study. Lancet Respir Med. 2022 Jun 14:S2213-2600(22)00169-2. doi: 10.1016/S2213-2600(22)00169-2. Epub ahead of print. PMID: 35714658; PMCID: PMC9197249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197249/ (Full text)

The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study

Abstract:

Background: Characterizing the post-COVID health conditions is helpful to direct patients to appropriate healthcare.

Aims: To describe the presence of symptoms in COVID-19 patients within 6 months after diagnosis and to investigate the associated factors in terms of reporting symptoms.

Methods: Data of DEU-COVIMER (a telephone interview-based COVID-19 follow-up center established in a tertiary care hospital) was analyzed for SARS-CoV-2 RNA positive participants aged ≥ 18 years from November 1st, 2020, to May 31st, 2021. Symptom frequencies were stratified by demographic and clinical characteristics at one, three, and 6 months after diagnosis. With the patients who had symptoms at baseline, generalized estimating equations were applied to identify the factors associated with reporting of symptoms.

Results: A total of 5610 patients agreed to participate in the study. Symptom frequency was 37.2%, 21.8%, and 18.2% for the first, third, and sixth months. Tiredness/fatigue, muscle or body aches, and dyspnea/difficulty breathing were the most common symptoms in all time frames. In multivariate analysis, older age, female gender (odds ratio OR 1.74, 95% confidence interval 1.57-1.93), bad economic status (OR 1.37, 1.14-1.65), current smoking (OR 1.15, 1.02-1.29), being fully vaccinated before COVID-19 (OR 0.53, 0.40-0.72), having more health conditions (≥ 3 conditions, OR 1.78, 1.33-2.37), having more symptoms (> 5 symptoms, OR 2.47, 2.19-2.78), and hospitalization (intensive care unit, OR 2.18, 1.51-3.14) were associated with reporting of symptoms.

Conclusions: This study identifies risk factors for patients who experience post-COVID-19 symptoms. Healthcare providers should appropriately allocate resources prioritizing the patients who would benefit from post-COVID rehabilitation.

Source: Emecen AN, Keskin S, Turunc O, Suner AF, Siyve N, Basoglu Sensoy E, Dinc F, Kilinc O, Avkan Oguz V, Bayrak S, Unal B. The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study. Ir J Med Sci. 2022 Jun 17:1–10. doi: 10.1007/s11845-022-03072-0. Epub ahead of print. PMID: 35715663; PMCID: PMC9205653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205653/ (Full text)

Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID

Abstract:

Objective: Musculoskeletal (MSK) pain is being increasingly reported by patients as one of the most common persistent symptoms in post-COVID-19 syndrome or Long COVID. However, there is a lack of understanding of its prevalence, characteristics, and underlying pathophysiological mechanisms. The objective of this review is to identify and describe the features and characteristics of MSK pain in Long COVID patients.

Methods: The narrative review involved a literature search of the following online databases: MEDLINE (OVID), EMBASE (OVID), CINAHL, PsyclNFO, and Web of Science (December 2019 to February 2022). We included observational studies that investigated the prevalence, characteristics, risk factors and mechanisms of MSK pain in Long COVID. After screening and reviewing the initial literature search results, a total of 35 studies were included in this review.

Results: The overall reported prevalence of MSK pain in Long COVID ranged widely from 0.3% to 65.2%. The pain has been reported to be localized to a particular region or generalized and widespread. No consistent pattern of progression of MSK pain symptoms over time was identified. Female gender and higher BMI could be potential risk factors for Long COVID MSK pain, but no clear association has been found with age and ethnicity. Different pathophysiological mechanisms have been hypothesized to contribute to MSK pain in Long COVID including increased production of proinflammatory cytokines, immune cell hyperactivation, direct viral entry of neurological and MSK system cells, and psychological factors.

Conclusion: MSK pain is one of the most common symptoms in Long COVID. Most of the current literature on Long COVID focuses on reporting the prevalence of persistent MSK pain. Studies describing the pain characteristics are scarce. The precise mechanism of MSK pain in Long COVID is yet to be investigated. Future research must explore the characteristics, risk factors, natural progression, and underlying mechanisms of MSK pain in Long COVID.

Source: Khoja O, Silva Passadouro B, Mulvey M, Delis I, Astill S, Tan AL, Sivan M. Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID. J Pain Res. 2022 Jun 17;15:1729-1748. doi: 10.2147/JPR.S365026. PMID: 35747600; PMCID: PMC9212788. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212788/ (Full text)

Self-Reported Long COVID in the General Population: Sociodemographic and Health Correlates in a Cross-National Sample

Abstract:

We aimed to gain knowledge of possible sociodemographic predictors of long COVID and whether long COVID was associated with health outcomes almost two years after the pandemic outbreak. There were 1649 adults who participated in the study by completing a cross-sectional online survey disseminated openly in Norway, the UK, the USA, and Australia between November 2021 and January 2022.

Participants were defined as having long COVID based on self-reports that they had been infected by COVID-19 and were experiencing long-lasting COVID symptoms. Logistic regression analyses were used to examine possible sociodemographic predictors, and multivariate analysis of variance was used to examine whether long COVID status was associated with health outcomes. None of the sociodemographic variables was significantly associated with reporting long COVID. Having long COVID was associated with higher levels of psychological distress, fatigue, and perceived stress. The effect of long COVID on health outcomes was greater among men than among women.

In conclusion, long COVID appeared across sociodemographic groups. People with long COVID reported worsened health outcomes compared to those who had had COVID-19 but without long-term symptoms. Men experiencing long COVID appear to be particularly vulnerable to experiencing poorer health outcomes; health services may pay extra attention to potentially unnoticed needs for support among men experiencing long COVID.

Source: Bonsaksen T, Leung J, Price D, Ruffolo M, Lamph G, Kabelenga I, Thygesen H, Geirdal AØ. Self-Reported Long COVID in the General Population: Sociodemographic and Health Correlates in a Cross-National Sample. Life (Basel). 2022 Jun 15;12(6):901. doi: 10.3390/life12060901. PMID: 35743932. https://www.mdpi.com/2075-1729/12/6/901/htm (Full text)

What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?: A Systematic Review

Abstract:

»: COVID-19 is a disease that is challenging science, health-care systems, and humanity. An astonishingly wide spectrum of manifestations of multi-organ damage, including musculoskeletal, can be associated with SARS-CoV-2.

»: In the acute phase of COVID-19, fatigue, myalgia, and arthralgia are the most common musculoskeletal symptoms.

»: Post-COVID-19 syndrome is a group of signs and symptoms that are present for >12 weeks. The associated musculoskeletal manifestations are fatigue, arthralgia, myalgia, new-onset back pain, muscle weakness, and poor physical performance.

»: Data on COVID-19 complications are growing due to large absolute numbers of cases and survivors in these 2 years of the pandemic. Additional musculoskeletal manifestations encountered are falls by the elderly, increased mortality after hip fracture, reduced bone mineral density and osteoporosis, acute sarcopenia, rhabdomyolysis, Guillain-Barré syndrome, muscle denervation atrophy, fibromyalgia, rheumatological disease triggering, septic arthritis, adhesive capsulitis, myositis, critical illness myopathy, onset of latent muscular dystrophy, osteonecrosis, soft-tissue abscess, urticarial vasculitis with musculoskeletal manifestations, and necrotizing autoimmune myositis.

»: A wide range of signs and symptoms involving the musculoskeletal system that affect quality of life and can result in a decrease in disability-adjusted life years. This powerful and unpredictable disease highlights the importance of multimodality imaging, continuing education, and multidisciplinary team care to support preventive measures, diagnosis, and treatment.

Source: Pires RE, Reis IGN, Waldolato GS, Pires DD, Bidolegui F, Giordano V. What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?: A Systematic Review. JBJS Rev. 2022 Jun 3;10(6). doi: 10.2106/JBJS.RVW.22.00013. PMID: 35658089. https://pubmed.ncbi.nlm.nih.gov/35658089/

Myopathy as a cause of fatigue in long-term post-COVID-19 symptoms: Evidence of skeletal muscle histopathology

Abstract:

Background: Among post-COVID-19 symptoms, fatigue is reported as one of the most common, even after mild acute infection, and as the cause of fatigue, myopathy diagnosed by electromyography has been proposed in previous reports. This study aimed to explore the histopathological changes in patients with post-COVID-19 fatigue.

Methods: Sixteen patients (mean age:46 years) with post-COVID-19 complaints of fatigue, myalgia or weakness persisting for up to 14 months were included. In all patients, quantitative electromyography and muscle biopsies analysed with light and electron microscopy were taken.

Results: Muscle weakness was present in 50%, myopathic electromyography in 75% while in all patients, there were histological changes. Muscle fiber atrophy was found in 38%, and 56% showed indications of fiber regeneration. Mitochondrial changes, comprising loss of COX activity, subsarcollemmal accumulation and/or abnormal cristae, were present in 62%. Inflammation was found in 62%, seen as T-lymphocytes and/or muscle fiber HLA-ABC expression. In 75%, capillaries were affected involving basal lamina and cells. In two patients, uncommon amounts of basal lamina were found, not only surrounding muscle fibers but also around nerves and capillaries.

Conclusions: The wide variety of histological changes in this study suggest that skeletal muscles may be a major target of SARS-CoV-2 causing muscular post-COVID-19 symptoms. The mitochondrial changes, inflammation and capillary injury in muscle biopsies can cause fatigue in part due to reduced energy supply. Since most patients had mild-moderate acute affection, the new variants that might cause less severe acute disease could still have the ability to cause long-term myopathy.

Source: Hejbøl EK, Harbo T, Agergaard J, Madsen LB, Pedersen TH, Østergaard LJ, Andersen H, Schrøder HD, Tankisi H. Myopathy as a cause of fatigue in long-term post-COVID-19 symptoms: Evidence of skeletal muscle histopathology. Eur J Neurol. 2022 Jun 6. doi: 10.1111/ene.15435. Epub ahead of print. PMID: 35661354.  https://pubmed.ncbi.nlm.nih.gov/35661354/ https://pubmed.ncbi.nlm.nih.gov/35661354/ (Full text available as PDF file)

COVID-19 Infection: Its Lingering Symptoms in Adults

Abstract:

Background: Recent studies showed that a significant percentage of people who recovered from coronavirus disease 2019 (COVID-19) had lingering symptoms. Among patients diagnosed with COVID-19 infection, studies showed persistent symptoms both in patients hospitalized and in outpatient settings. In the studies done in the outpatient setting involving mild to moderate COVID-19 patients, there were significant variations regarding the exact percentage of people with lingering symptoms. Also, in the outpatient setting, not many studies were done on COVID-19 patients that assessed risk factors for having lingering symptoms. Given that a large percentage of people infected with COVID-19 infection do not get hospitalized, it is imperative that this lacuna be filled. We believe knowing the details of long-term symptoms of COVID-19 infection both from prevalence and predictors point of view, could allow the physicians, healthcare system and community to better prepare for managing and following these patients.

Materials and methods: Our study period was within 12 months after the first documented case of COVID-19 occurred in the State of Alabama. Our study population included patients who were diagnosed with a documented case of COVID-19 in this time period and were under the care of a single primary care provider at an ambulatory clinic. Among 80 patients who had documented COVID-19, three left the practice, two declined to participate in the study and three were deceased (two due to COVID-19 and one for other reasons). Therefore, the study population constituted 72 patients. A questionnaire was mailed to all 72 patients to see how many of them had symptoms three months and beyond of having COVID-19 infection. A chart review was conducted for the study participants to assess for “Comorbid conditions”, health conditions that were considered conclusively high risk for acute COVID-19 infection by US Center for Disease Control and Prevention (CDC).

Results: Fifty-three patients responded to the questionnaire; 27 patients (50.9%) reported lingering symptoms beyond three months of diagnosis with COVID-19 infection. The three most common symptoms reported were fatigue (56%), brain fog (48%), and shortness of breath (41%). The results also showed that women are more likely than men to have lingering symptoms. “Elderly” (≥65 years) patients were as likely as 18-64 years old patients to have lingering symptoms and the presence of one or more of the “Comorbid conditions” does not have any bearing on the occurrence of lingering symptoms.

Conclusion: Future studies should be done in a larger population to assess the findings that our study showed regarding “elderly” age and the presence of one or more “comorbid conditions” being independent variables of the occurrence of prolonged COVID-19 symptoms. We recommend studies be done assessing the prevalence and predictors for the long-term effects of the COVID-19 infection. This knowledge could help in preventing those long-term symptoms from occurring in the first place and also in preparing the patient, the physician and the community in managing the outcomes effectively.

Source: Yellumahanthi DK, Barnett B, Barnett S, Yellumahanthi S. COVID-19 Infection: Its Lingering Symptoms in Adults. Cureus. 2022 May 4;14(5):e24736. doi: 10.7759/cureus.24736. PMID: 35677013; PMCID: PMC9166577. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166577/ (Full text)

Inflammation during early post-acute COVID-19 is associated with reduced exercise capacity and Long COVID symptoms after 1 year

Abstract:

Background: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.

Methods: We performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection in the UCSF Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; NCT04362150 ) and correlated findings with previously measured biomarkers. We used logistic regression to estimate associations with PASC symptoms (dyspnea, chest pain, palpitations, and fatigue) adjusted for confounders and linear regression to estimate differences between those with and without symptoms adjusted for confounders.

Results: Out of 120 participants in the cohort, 46 participants (unselected for symptom status) had at least one advanced cardiac test performed at median 17 months following initial SARS-CoV-2 infection. Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), higher extracellular volume was associated with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/23 (57%) with cardiopulmonary symptoms or fatigue had reduced exercise capacity (peak VO 2 <85% predicted) compared to 2/16 (13%) without symptoms (p=0.008). The adjusted difference in peak VO 2 was 5.9 ml/kg/min lower (-9.6 to -2.3; p=0.002) or -21% predicted (-35 to -7; p=0.006) among those with symptoms. Chronotropic incompetence was the primary abnormality among 9/15 (60%) with reduced peak VO 2 . Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Inflammatory markers (hsCRP, IL-6, TNF-α) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO 2 more than 1 year later.

Conclusions: Cardiopulmonary symptoms and elevated inflammatory markers present early in PASC are associated with objectively reduced exercise capacity measured on cardiopulmonary exercise testing more than 1 year following COVID-19. Chronotropic incompetence may explain reduced exercise capacity among some individuals with PASC.

Clinical perspective: What is New? Elevated inflammatory markers in early post-acute COVID-19 are associated with reduced exercise capacity more than 1 year later. Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection. Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRI findings argue against myocardial dysfunction and myocarditis.

Clinical implications: Cardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or “Long COVID” should be performed in a manner that allows for assessment of heart rate response to exercise. Therapeutic trials of anti-inflammatory and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

Source: Durstenfeld MS, Peluso MJ, Kaveti P, Hill C, Li D, Sander E, Swaminathan S, Arechiga VM, Sun K, Ma Y, Zepeda V, Lu S, Goldberg SA, Hoh R, Chenna A, Yee BC, Winslow JW, Petropoulos CJ, Win S, Kelly JD, Glidden DV, Henrich TJ, Martin JN, Lee YJ, Aras MA, Long CS, Grandis DJ, Deeks SG, Hsue PY. Inflammation during early post-acute COVID-19 is associated with reduced exercise capacity and Long COVID symptoms after 1 year. medRxiv [Preprint]. 2022 Jun 1:2022.05.17.22275235. doi: 10.1101/2022.05.17.22275235. PMID: 35677073; PMCID: PMC9176659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176659/ (Full text)