Tag: long covid symptoms

Reduced Muscle Strength in Patients with Long-COVID-19 Syndrome Is Mediated by Limb Muscle Mass

Abstract:

Understanding the impact of COVID-19 on muscle strength may help to elucidate the organ systems that contribute to acute and chronic COVID-19 sequelae. We questioned whether patients with postdischarge symptoms after COVID-19 had compromised muscle strength compared with a control group, and if this potential relationship was mediated by the lower appendicular lean mass index (ALMI).

A total of 99 patients with long-COVID-19 and 97 control participants were screened. Maximal grip strength was assessed with a TKK 5101 digital dynamometer, and leg extension 1RM was measured using EGYM Smart Strength machines. Body composition (fat mass percentage, lean mass, visceral fat and appendicular lean mass index) was determined using a whole-body dual-energy X-ray densitometer.

Results showed that grip strength and leg extension strength were significantly higher in controls than in COVID-19 survivors (mean [SD], 32.82 [10.01] vs. 26.94 [10.33] kg; difference, 5.87 kg; P < 0.001) and (mean [SD], 93.98 [33.73] vs. 71.59 [33.70] kg; difference, 22.38 kg; P < 0.001), respectively). The relationship between long-COVID syndrome and grip/leg strength levels was partly mediated by ALMI, which explained 52% of the association for grip strength and 39% for leg extension.

Our findings provide novel insights into the mechanisms underlying the relationship between long-COVID syndrome and grip/leg strength levels, supporting the negative effects of long-COVID syndrome on muscle function.

Source: Ramírez-Vélez R, Legarra-Gorgoñon G, Oscoz-Ochandorena S, García-Alonso Y, García-Alonso N, Oteiza J, Ernaga Lorea A, Correa-Rodríguez M, Izquierdo M. Reduced Muscle Strength in Patients with Long-COVID-19 Syndrome Is Mediated by Limb Muscle Mass. J Appl Physiol (1985). 2022 Nov 30. doi: 10.1152/japplphysiol.00599.2022. Epub ahead of print. PMID: 36448687. https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00599.2022 (Full text available as PDF file)

Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome

Abstract:

Background: Post Exertional Symptom Exacerbation (PESE) is a characteristic symptom of Post-COVID Syndrome (PCS).

Objectives: This prospective study investigated the effect of a 6-week structured World Health Organisation (WHO) Borg CR-10 5-phase pacing protocol on PESE episodes and quality of life in a cohort of individuals with long-standing PCS (average duration of symptoms was 17 months).

Methods: Participants received weekly telephone calls with a clinician to complete the Leeds PESE Questionnaire (LPQ) and identify the appropriate phase of the pacing protocol. EQ-5D 5L was completed at the intervention’s beginning and end to measure overall health.

Results: Thirty-one participants completed the 6-week protocol, with a statistically and clinically significant reduction in the average number of PESE episodes (from 3.4 episodes in week one to 1.1 in week six), with an average decrease of 16% (95% CI: 9% to 24%; p<0.001) each week, and reduction across all three exertional triggers (physical, cognitive, and emotional). Physical activity levels showed moderate improvements during the intervention period. Mean EQ-5D 5L scores improved from 51.4 points to 60.6 points (paired difference of 9.2 points, 95% CI: 3.2 to 15.2 points; p=0.004).

Conclusions: A structured pacing protocol significantly reduces PESE episodes and improves overall health in PCS.

Source: Parker M, Sawant HB, Flannery T, Tarrant R, Shardha J, Bannister R, Ross D, Halpin S, Greenwood DC, Sivan M. Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome. J Med Virol. 2022 Dec 2. doi: 10.1002/jmv.28373. Epub ahead of print. PMID: 36461167. https://pubmed.ncbi.nlm.nih.gov/36461167/

Impact of pre-existing chronic viral infection and reactivation on the development of long COVID

Abstract:

Background: The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.

Methods: In a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status), and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.

Results: We observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen (EBNA) IgG levels, but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52).

Conclusion: Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.

Trial registration: Long-term Impact of Infection with Novel Coronavirus (LIINC); NCT04362150FUNDING. This work was supported by the National Institute of Allergy and Infectious Diseases NIH/NIAID 3R01AI141003-03S1 to TJ Henrich, R01AI158013 to M Gandhi and M Spinelli, K24AI145806 to P Hunt, and by the Zuckerberg San Francisco Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine. MJP is supported on K23 A137522 and received support from the UCSFBay Area Center for AIDS Research (P30-AI027763).

Source: Peluso MJ, Deveau TM, Munter SE, Ryder DM, Buck AM, Beck-Engeser G, Chan F, Lu S, Goldberg SA, Hoh R, Tai V, Torres L, Iyer NS, Deswal M, Ngo LH, Buitrago M, Rodriguez AE, Chen JY, Yee BC, Chenna A, Winslow JW, Petropoulos CJ, Deitchman AN, Hellmuth J, Spinelli MA, Durstenfeld MS, Hsue PY, Kelly JD, Martin JN, Deeks SG, Hunt PW, Henrich TJ. Impact of pre-existing chronic viral infection and reactivation on the development of long COVID. J Clin Invest. 2022 Dec 1:e163669. doi: 10.1172/JCI163669. Epub ahead of print. PMID: 36454631. https://www.jci.org/articles/view/163669 (Full text)

Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients

Abstract:

The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies.

A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months.

The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2-61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.

Source: Di Gennaro F, Belati A, Tulone O, Diella L, Fiore Bavaro D, Bonica R, Genna V, Smith L, Trott M, Bruyere O, Mirarchi L, Cusumano C, Dominguez LJ, Saracino A, Veronese N, Barbagallo M. Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients. Intern Emerg Med. 2022 Nov 30:1–9. doi: 10.1007/s11739-022-03164-w. Epub ahead of print. PMID: 36449260; PMCID: PMC9709360. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709360/ (Full text)

Long COVID: mechanisms, risk factors and recovery

Abstract:

New findings: What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies.

Abstract: Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS-CoV-2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery.

This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes.

The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID-related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve.

We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro-clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations.

Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.

Source: Astin R, Banerjee A, Baker MR, Dani M, Ford E, Hull JH, Lim PB, McNarry M, Morten K, O’Sullivan O, Pretorius E, Raman B, Soteropoulos DS, Taquet M, Hall CN. Long COVID: mechanisms, risk factors and recovery. Exp Physiol. 2022 Nov 22. doi: 10.1113/EP090802. Epub ahead of print. PMID: 36412084. https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP090802 (Full text)

Mild SARS-CoV-2 infection results in long-lasting microbiota instability

Abstract:

Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of SARS-CoV-2 infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting. To address this knowledge gap, we longitudinally sampled 14 SARS-CoV-2 positive subjects who remained outpatient and 4 household controls. SARS-CoV-2 cases exhibited a significantly less stable gut microbiota relative to controls, as long as 154 days after their positive test. These results were confirmed and extended in the K18-hACE2 mouse model, which is susceptible to SARS-CoV-2 infection. All of the tested SARS-CoV-2 variants significantly disrupted the mouse gut microbiota, including USA-WA1/2020 (the original variant detected in the United States), Delta, and Omicron. Surprisingly, despite the fact that the Omicron variant caused the least severe symptoms in mice, it destabilized the gut microbiota and led to a significant depletion in Akkermansia muciniphila. Furthermore, exposure of wild-type C57BL/6J mice to SARS-CoV-2 disrupted the gut microbiota in the absence of severe lung pathology.

IMPORTANCE Taken together, our results demonstrate that even mild cases of SARS-CoV-2 can disrupt gut microbial ecology. Our findings in non-hospitalized individuals are consistent with studies of hospitalized patients, in that reproducible shifts in gut microbial taxonomic abundance in response to SARS-CoV-2 have been difficult to identify. Instead, we report a long-lasting instability in the gut microbiota. Surprisingly, our mouse experiments revealed an impact of the Omicron variant, despite producing the least severe symptoms in genetically susceptible mice, suggesting that despite the continued evolution of SARS-CoV-2 it has retained its ability to perturb the intestinal mucosa. These results will hopefully renew efforts to study the mechanisms through which Omicron and future SARS-CoV-2 variants alter gastrointestinal physiology, while also considering the potentially broad consequences of SARS-CoV-2-induced microbiota instability for host health and disease.

Source: Vaibhav Upadhyay, Rahul Suryawanshi, Preston Tasoff, Maria McCavitt-Malvido, G. Renuka Kumar, Victoria Wong Murray, Cecilia Noecker, Jordan E. Bisanz, Yulin Hswen, Connie Ha, Bharat Sreekumar, Irene P. Chen, Susan V Lynch, Melanie Ott, Sulggi Lee, Peter J. Turnbaugh. Mild SARS-CoV-2 infection results in long-lasting microbiota instability. bioRxiv 2022.12.07.519508; doi: https://doi.org/10.1101/2022.12.07.519508  https://www.biorxiv.org/content/10.1101/2022.12.07.519508v1.full (Full text)

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor?

Objective: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition.

Methods: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated.

Results: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue.

Conclusions: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Source: Azcue N, Gómez-Esteban JC, Acera M, Tijero B, Fernandez T, Ayo-Mentxakatorre N, Pérez-Concha T, Murueta-Goyena A, Lafuente JV, Prada Á, López de Munain A, Ruiz-Irastorza G, Ribacoba L, Gabilondo I, Del Pino R. Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder? J Transl Med. 2022 Dec 6;20(1):569. doi: 10.1186/s12967-022-03764-2. PMID: 36474290. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03764-2 (Full text)

Impaired pulmonary and muscle function during moderate exercise in female patients recovered from SARS-CoV-2

Abstract:

This study aimed to assess pulmonary and muscle dysfunction by analyzing the slow component of oxygen uptake (VO2SC), and mechanical and ventilatory efficiency in adult women recovered from the severe acute respiratory syndrome coronavirus type II (SARS-CoV-2) during a constant load test. 32 women (N = 17 patients with SARS-CoV-2; N = 15 control group) performed two cardiopulmonary exercise tests (CPX) on a cycle ergometer.

In the first test, the participants performed incremental CPX until extenuation. In the second test the participants performed a 10-min CPX at a constant load intensity (watts) corresponding to the first ventilatory threshold. There was a 48-72 h rest period between the two tests. There was a significant increase in the VO2SC in the patients recovered from SARS-CoV-2 (160.4 ± 60 mL min-1) in comparison with the healthy participants (59.6 ± 65 mL min-1) (P < 0.001).

Mechanical efficiency significantly decreased in patients recovered from SARS-CoV-2 compared to the control group (P = 0.04). Ventilatory inefficiency significantly increased in the patients recovered from SARS-CoV-2 compared with the control group (P < 0.001). Adult women recovered from SARS-CoV-2 infection have important pulmonary and muscular dysfunction and fatigue which contributes to increasing the VO2SC and reducing mechanical and ventilatory efficiency during mild-moderate exercise at a constant load.

Source: Pleguezuelos E, Del Carmen A, Moreno E, Ortega P, Robles A, Serra-Prat M, Miravitlles M, Yebenes JC, Garnacho-Castaño MV. Impaired pulmonary and muscle function during moderate exercise in female patients recovered from SARS-CoV-2. Sci Rep. 2022 Dec 4;12(1):20943. doi: 10.1038/s41598-022-24941-9. PMID: 36464697.  https://www.nature.com/articles/s41598-022-24941-9 (Full text)

Persistent alveolar type 2 dysfunction and lung structural derangement in post-acute COVID-19

Abstract:

SARS-CoV-2 infection can manifest as a wide range of respiratory and systemic symptoms well after the acute phase of infection in over 50% of patients. Key questions remain on the long-term effects of infection on tissue pathology in recovered COVID-19 patients. To address these questions we performed multiplexed imaging of post-mortem lung tissue from 12 individuals who died post-acute COVID-19 (PC) and compare them to lung tissue from patients who died during the acute phase of COVID-19, or patients who died with idiopathic pulmonary fibrosis (IPF), and otherwise healthy lung tissue.

We find evidence of viral presence in the lung up to 359 days after the acute phase of disease, including in patients with negative nasopharyngeal swab tests. The lung of PC patients are characterized by the accumulation of senescent alveolar type 2 cells, fibrosis with hypervascularization of peribronchial areas and alveolar septa, as the most pronounced pathophysiological features. At the cellular level, lung disease of PC patients, while distinct, shares pathological features with the chronic pulmonary disease of IPF. which may help rationalize interventions for PC patients.

Altogether, this study provides an important foundation for the understanding of the long-term effects of SARS-CoV-2 pulmonary infection at the microanatomical, cellular, and molecular level.

Source: André F. Rendeiro, Hiranmayi Ravichandran, Junbum Kim, Alain C. Borczuk, Olivier Elemento, Robert E. Schwartz. Persistent alveolar type 2 dysfunction and lung structural derangement in post-acute COVID-19. medRxiv 2022.11.28.22282811; doi: https://doi.org/10.1101/2022.11.28.22282811 https://www.medrxiv.org/content/10.1101/2022.11.28.22282811v1.full-text  (Full text)

Identifying Profiles and Symptoms of Patients With Long COVID in France: Data Mining Infodemiology Study Based on Social Media

Abstract:

Background: Long COVID-a condition with persistent symptoms post COVID-19 infection-is the first illness arising from social media. In France, the French hashtag #ApresJ20 described symptoms persisting longer than 20 days after contracting COVID-19. Faced with a lack of recognition from medical and official entities, patients formed communities on social media and described their symptoms as long-lasting, fluctuating, and multisystemic. While many studies on long COVID relied on traditional research methods with lengthy processes, social media offers a foundation for large-scale studies with a fast-flowing outburst of data.

Objective: We aimed to identify and analyze Long Haulers’ main reported symptoms, symptom co-occurrences, topics of discussion, difficulties encountered, and patient profiles.

Methods: Data were extracted based on a list of pertinent keywords from public sites (eg, Twitter) and health-related forums (eg, Doctissimo). Reported symptoms were identified via the MedDRA dictionary, displayed per the volume of posts mentioning them, and aggregated at the user level. Associations were assessed by computing co-occurrences in users’ messages, as pairs of preferred terms. Discussion topics were analyzed using the Biterm Topic Modeling; difficulties and unmet needs were explored manually. To identify patient profiles in relation to their symptoms, each preferred term’s total was used to create user-level hierarchal clusters.

Results: Between January 1, 2020, and August 10, 2021, overall, 15,364 messages were identified as originating from 6494 patients of long COVID or their caregivers. Our analyses revealed 3 major symptom co-occurrences: asthenia-dyspnea (102/289, 35.3%), asthenia-anxiety (65/289, 22.5%), and asthenia-headaches (50/289, 17.3%). The main reported difficulties were symptom management (150/424, 35.4% of messages), psychological impact (64/424,15.1%), significant pain (51/424, 12.0%), deterioration in general well-being (52/424, 12.3%), and impact on daily and professional life (40/424, 9.4% and 34/424, 8.0% of messages, respectively). We identified 3 profiles of patients in relation to their symptoms: profile A (n=406 patients) reported exclusively an asthenia symptom; profile B (n=129) expressed anxiety (n=129, 100%), asthenia (n=28, 21.7%), dyspnea (n=15, 11.6%), and ageusia (n=3, 2.3%); and profile C (n=141) described dyspnea (n=141, 100%), and asthenia (n=45, 31.9%). Approximately 49.1% of users (79/161) continued expressing symptoms after more than 3 months post infection, and 20.5% (33/161) after 1 year.

Conclusions: Long COVID is a lingering condition that affects people worldwide, physically and psychologically. It impacts Long Haulers’ quality of life, everyday tasks, and professional activities. Social media played an undeniable role in raising and delivering Long Haulers’ voices and can potentially rapidly provide large volumes of valuable patient-reported information. Since long COVID was a self-titled condition by patients themselves via social media, it is imperative to continuously include their perspectives in related research. Our results can help design patient-centric instruments to be further used in clinical practice to better capture meaningful dimensions of long COVID.

Source: Déguilhem A, Malaab J, Talmatkadi M, Renner S, Foulquié P, Fagherazzi G, Loussikian P, Marty T, Mebarki A, Texier N, Schuck S. Identifying Profiles and Symptoms of Patients With Long COVID in France: Data Mining Infodemiology Study Based on Social Media. JMIR Infodemiology. 2022 Nov 22;2(2):e39849. doi: 10.2196/39849. PMID: 36447795; PMCID: PMC9685517.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685517/ (Full text)