Tag: long Covid

What do infectious disease specialists think about managing long COVID?

Abstract:

This survey of infectious disease providers on long COVID care revealed a lack of familiarity with existing resources, a sentiment of missing guidelines, and scarcity of dedicated care centers. The low response rate suggests that infectious disease specialists do not consider themselves as the primary providers of long COVID care.

Long COVID (or post-acute sequelae of COVID-19, PASC) complicates an estimated 10–30% of non-hospitalized cases and 50–70% of hospitalized cases of acute SARS-CoV-2 infection.(Reference Davis, McCorkell, Vogel and Topol1) The work-up often requires multiple disciplines to collaborate, both for diagnostic evaluation and for offering symptomatic treatment.(Reference Parker, Brigham and Connolly2) For this purpose, an infrastructure of so-called long COVID clinics has been developing,(Reference Vanichkachorn, Newcomb and Cowl3) oftentimes under the supervision of a single medical specialty. Given that long COVID is a complication of an infection, the medical subspecialty of infectious diseases (ID) has frequently been involved in devising and running such clinics. Here, we intended to survey ID providers in North America regarding their role in managing long COVID and their perspective on the availability of resources. For this purpose, we used the Emerging Infections Network (EIN), which is a provider-based sentinel network funded by the Infectious Diseases Society of America and the Centers for Disease Control and Prevention (http://ein.idsociety.org/). Our implicit hypothesis was that ID providers are insufficiently equipped to provide long COVID care because neither infection work-up nor antiviral treatment play a role in current management.

We designed a questionnaire, tested it among peers, and sent it out to all 2,978 EIN listserv subscribers on 3 occasions between February 7 and February 26, 2023. The survey contained 8 questions, 7 of which were structured questions. There was an option to make additional open-text field comments.

The response rate was very low, with 117 of 2,978 providers who filled out the survey (3.9%). Of these 117, 46 stated that they did not care for long COVID patients, and we analyzed the responses of the remaining 71 providers (2.4% of 2,978). Most of these would see long COVID patients once a month or less often (50/71). Thirteen indicated they were specifically seeing long COVID patients. Only 15 out of 71 (21%) felt “very comfortable” in making a diagnosis of long COVID, and most thought the resources available to clinicians involved in long COVID care were inadequate (55%) or were unaware of such resources (18%). The management consists mostly of a case-by-case-based approach without standardization (55%), followed by behavioral education for energy conservation (44%). Access to a long COVID clinic was considered easy by only 17%, while 48% stated there was no dedicated clinic located nearby, and 35% highlighted that locally available clinics were not easily accessible.

The open-text field answers were notable for showing that long COVID is a “complicated syndrome, currently without a specialty home” and that it is not easy to provide “holistic care to patients in our existing system.” Also, the absence of straightforward definitions, national guidelines, and dedicated research was pointed out. Lastly, one provider argued that “this is a primary care issue with collaboration with any needed specialists.”

The low response rate, the small percentage of ID providers heavily involved in long COVID care, and some free text statements can be seen as key findings of our survey. Our interpretation is that long COVID—although originating from an acute infection—is not perceived to be in the wheelhouse of the infectious diseases subspecialty. Infectious disease providers may not consider themselves as well-equipped as a generalist such as primary care providers.(Reference Berger, Altiery, Assoumou and Greenhalgh4) Long COVID patients, however, are likely to benefit from designated points of generalist care, with access to pertinent medical specialties and rehabilitative services (physical therapy, occupational health, and mental health), in order to receive comprehensive management for their signs and symptoms. In addition, widespread healthcare worker burnout in the wake of the pandemic may contribute to a subjective saturation with COVID-19-related topics and have reduced survey participation.

A minority of responders considered themselves very comfortable in diagnosing long COVID, the resources for appropriate clinical care were mostly felt to be inadequate, and management seems to happen on a case-by-case base (i.e., non-standardized). This points to the general unease about what constitutes best practice in long COVID care. We speculate that similar findings would be encountered in other medical specialties. Also, there is a considerable need for more research in the field, as evidenced by a recent award by the Agency for Healthcare Research and Quality to study new models of delivery of long COVID care (https://www.ahrq.gov/coronavirus/long-covid-grant-awards.html).

In conclusion, our survey of infectious disease providers and their perspective on long COVID care suggested a lack of familiarity with existing resources, a sentiment of missing guidelines, and scarcity of dedicated care centers. In addition, the low response rate to this survey can be interpreted as ID providers not regarding their specialty as the primary point of contact for delivering long COVID care.

Source: Lyons MD, Beekmann SE, Polgreen PM, Marschall J. What do infectious disease specialists think about managing long COVID? Antimicrobial Stewardship & Healthcare Epidemiology. 2023;3(1):e236. doi:10.1017/ash.2023.519 https://www.cambridge.org/core/journals/antimicrobial-stewardship-and-healthcare-epidemiology/article/what-do-infectious-disease-specialists-think-about-managing-long-covid/E89D7EA86E873D517D24FBB20D304A8D (Full text)

 

Smartphone-based evaluation of static balance and mobility in long-lasting COVID-19 patients

Abstract:

Background: SARS-CoV-2 infection can lead to a variety of persistent sequelae, collectively known as long COVID-19. Deficits in postural balance have been reported in patients several months after COVID-19 infection. The purpose of this study was to evaluate the static balance and balance of individuals with long COVID-19 using inertial sensors in smartphones.

Methods: A total of 73 participants were included in this study, of which 41 had long COVID-19 and 32 served as controls. All participants in the long COVID-19 group reported physical complaints for at least 7 months after SARS-CoV-2 infection. Participants were evaluated using a built-in inertial sensor of a smartphone attached to the low back, which recorded inertial signals during a static balance and mobility task (timed up and go test). The parameters of static balance and mobility obtained from both groups were compared.

Results: The groups were matched for age and BMI. Of the 41 participants in the long COVID-19 group, 22 reported balance impairment and 33 had impaired balance in the Sharpened Romberg test. Static balance assessment revealed that the long COVID-19 group had greater postural instability with both eyes open and closed than the control group. In the TUG test, the long COVID-19 group showed greater acceleration during the sit-to-stand transition compared to the control group.

Conclusion: The smartphone was feasible to identify losses in the balance motor control and mobility of patients with long-lasting symptomatic COVID-19 even after several months or years. Attention to the balance impairment experienced by these patients could help prevent falls and improve their quality of life, and the use of the smartphone can expand this monitoring for a broader population.

Source: Corrêa BDC, Santos EGR, Belgamo A, Pinto GHL, Xavier SS, Silva CC, Dias ÁRN, Paranhos ACM, Cabral ADS, Callegari B, Costa E Silva AA, Quaresma JAS, Falcão LFM, Souza GS. Smartphone-based evaluation of static balance and mobility in long-lasting COVID-19 patients. Front Neurol. 2023 Dec 11;14:1277408. doi: 10.3389/fneur.2023.1277408. PMID: 38148981; PMCID: PMC10750373. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10750373/ (Full text)

Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome

Abstract:

Introduction: While there is sufficient information about acute COVID-19, which can cause a multisystemic and fatal disease, post-COVID syndrome and risk factors for this condition remain poorly known. We aimed to identify postCOVID symptoms and risk factors for chronic post-COVID syndrome through this study.

Materials and methods: This prospective cross-sectional study was conducted on 254 out of 384 COVID-19 patients admitted to our COVID-19 polyclinic between February and April 2021. The patients were questioned with a list of 37 symptoms at the fifth and twelfth weeks after disease onset via phone review, and their acute post-COVID (APC) and chronic post-COVID (CPC) symptoms were recorded. Data on risk factors were collected from the hospital’s medical records system. Associations between symptom count in the CPC phase and age, sex, hospitalization, RT-PCR result, specific radiological findings, comorbidities, and long-term medications were evaluated.

Result: Two hundred twenty-one patients had APC symptoms, and 138 patients had CPC symptoms. While the most common symptom was fatigue at week five, it was hair loss at week 12. Symptoms were observed significantly less in the CPC phase than in the APC phase (Z= -12.301, p= 0.00). Female sex and the presence of specific radiological findings were significantly associated with the occurrence of CPC symptoms (p= 0.03, p= 0.00, respectively). Long-term use of angiotensin-2 receptor blockers (ARBs) was correlated with a low symptom count in the CPC phase (p= 0.00).

Conclusions: Female sex and the presence of specific radiological findings were risk factors for developing CPC. Long-term use of ARBs was associated with a low chronic post-COVID symptom burden. A substantial cluster of multisystemic symptoms was observed in both phases, and this condition highlights the requirement for customized outpatient management that includes long-term follow-up and treatment of COVID-19 patients. Identifying the high-risk patients that will develop persistent symptoms can guide this management.

Source: Abalı H, Demir D, Gül Ş, Şimşek Veske N, Tural Onur S. Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome. Tuberk Toraks. 2023 Dec;71(4):378-389. English. doi: 10.5578/tt.20239606. PMID: 38152008. https://pubmed.ncbi.nlm.nih.gov/38152008/ (Full text available as PDF file)

Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

Abstract:

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin.

This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Source: Chambers, P.W.; Chambers, S.E. Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach. Preprints 2023, 2023121881. https://doi.org/10.20944/preprints202312.1881.v2 https://www.preprints.org/manuscript/202312.1881/v2 (Full text available as PDF file)

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series

Highlights:

• Both Long COVID and ME/CFS are characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα.

• In a small Long COVID and ME/CFS case series, patients’ immune deficiency and health improve during treatment period with a nebulized antioxidant, anti-pathogen and immune-modulatory pharmacological agent.

• This work provides evidence of a useful biomarker, CD8 T-cell dysfunction reminiscent of T cell exhaustion, that may assist diagnosis and have utility for tracking disease outcome during therapy, including response to a potential new treatment.

Abstract:

Background: Patients with post-acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC, i.e., Long COVID) have a symptom complex highly analogous to many features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting they may share some aspects of pathogenesis in these similar disorders. ME/CFS is a complex disease affecting numerous organ systems and biological processes and is often preceded by an infection-like episode. It is postulated that the chronic manifestations of illness may result from an altered host response to infection or inability to resolve inflammation, as is being reported in Long COVID. The immunopathogenesis of both disorders is still poorly understood. Here, we show data that suggest Long COVID and ME/CFS may be due to an aberrant response to an immunological trigger-like infection, resulting in a dysregulated immune system with CD8 T-cell dysfunction reminiscent of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress. As there is an urgent need for diagnostic tools and treatment strategies for these two related disabling disorders, here, in a retrospective case series, we have also identified a potential nebulized antioxidant/anti-pathogen treatment that has evidence of a good safety profile. This nebulized agent is comprised of five ingredients previously reported individually to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. Administration of this treatment by nebulizer results in rapid access of small doses of well-studied antioxidants and agents with anti-pathogen potential to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system.

Methods and Findings: We conducted an analysis of CD8 T-cell function and severity of symptoms by self-report questionnaires in ME/CFS, Long COVID and healthy controls. We developed a CD8 T-cell functional assay, assessing CD8 T-cell dysfunction by intracellular cytokine staining (ICS) in a group of ME/CFS (n = 12) and Long COVID patients (n = 8), comparing to healthy controls (HC) with similar age and sex (n = 10). Magnet-enriched fresh CD8 T-cells in both patient groups had a significantly diminished capacity to produce both cytokines, IFNγ or TNFα, after PMA stimulation when compared to HC. The symptom severity questionnaire showed similar symptom profiles for the two disorders. Fortuitously, through a retrospective case series, we were able to examine the ICS and questionnaire data of 4 ME/CFS and 4 Long COVID patients in conjunction with their treatment (3–15 months). In parallel with the treatment pursued electively by participants in this retrospective case series, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%. No serious treatment-associated side effects or laboratory anomalies were noted in these patients.

Conclusions: Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an immunomodulatory, antioxidant pharmacological treatment with anticipated anti-pathogen activity. This work provides evidence of the potential utility of a biomarker, CD8 T-cell dysfunction, and suggests the potential for benefit from a new nebulized antioxidant/anti-pathogen treatment. These immune biomarker data may help build capacity for improved diagnosis and tracking of treatment outcomes during clinical trials for both Long COVID and ME/CFS while providing clues to new treatment avenues that suggest potential efficacy for both conditions.

Source: Gil, A., Hoag, G.E., Salerno, J.P., Hornig, M., Klimas, N., Selin, L.K. Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/antipathogen agent in a retrospective case series. Brain, Behavior, & Immunity – Health (2024), doi: https://doi.org/10.1016/j.bbih.2023.100720 https://www.sciencedirect.com/science/article/pii/S2666354623001345 (Full text)

Muscle abnormalities worsen after post-exertional malaise in long COVID

Abstract:

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear.

With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Source: Appelman, B., Charlton, B.T., Goulding, R.P. et al. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nat Commun 15, 17 (2024). https://doi.org/10.1038/s41467-023-44432-3 https://www.nature.com/articles/s41467-023-44432-3 (Full text)

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

Abstract:

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders.
Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.
Source: Mantle D, Hargreaves IP, Domingo JC, Castro-Marrero J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. International Journal of Molecular Sciences. 2024; 25(1):574. https://doi.org/10.3390/ijms25010574 https://www.mdpi.com/1422-0067/25/1/574 (Full text)

A Mechanistic Model for Long COVID Dynamics

Abstract:

Long COVID, a long-lasting disorder following an acute infection of COVID-19, represents a significant public health burden at present. In this paper, we propose a new mechanistic model based on differential equations to investigate the population dynamics of long COVID. By connecting long COVID with acute infection at the population level, our modeling framework emphasizes the interplay between COVID-19 transmission, vaccination, and long COVID dynamics. We conducted a detailed mathematical analysis of the model. We also validated the model using numerical simulation with real data from the US state of Tennessee and the UK.

Source: Derrick J, Patterson B, Bai J, Wang J. A Mechanistic Model for Long COVID Dynamics. Mathematics (Basel). 2023 Nov;11(21):4541. doi: 10.3390/math11214541. Epub 2023 Nov 3. PMID: 38111916; PMCID: PMC10727852. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10727852/ (Full text)

Profound Symptom Alleviation in Long-Covid Patients After PAMP-Immunotherapy: Three Case Reports

Abstract:

Background: Long-Covid patients suffer from a range of symptoms with a largely varying degree of severity, including chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), post-exertional malaise (PEM), postural orthostatic tachycardia syndrome (POTS), loss of smell and/or taste, cough, shortness of breath, headache, muscle ache, sleep disturbance, cognitive dysfunction, and depression.

Treatment: PAMP-immunotherapy was developed by one of us (UH), inspired by the old fever therapy a century ago, to treat cancer patients. Unintentionally, in three cases of Long-Covid, quick and profound symptom alleviation could be observed after only a few PAMP treatments.

Conclusion: PAMP-immunotherapy might be a treatment option for Long-Covid patients which is surprisingly brief, cheap, and effective.

Source: Raphaela Gaudek, Holger Porath, Uwe Hobohm. (2023). [Case Report] Profound Symptom Alleviation in Long-Covid Patients After PAMP-Immunotherapy: Three Case Reports. Qeios. doi:10.32388/69I32L. https://www.qeios.com/read/69I32L (Full text)

Data-driven prognosis of long COVID in patients using machine learning

Abstract:

Long-COVID is a health condition in which individuals experience persisting, returning or new symptoms longer than 4 weeks after they have recovered from COVID-19 and this condition can even last for months. It can cause multi-organ failure and in some cases, it can even lead to death. The effects and symptoms of Long COVID can vary from person to person. Even though it’s rising globally, there is a limited understanding about its prediction, risk factors and whether its prognosis can be predicted in the initial first week of acute COVID-19. Artificial Intelligence (AI) and Machine Learning (ML) have aided the medical industry in a variety of ways including the diagnosis, prediction, and prognosis of many diseases.

This paper introduces a novel method to determine Long COVID in the early or first week of acute COVID-19 by considering the basic demographics, and symptoms during COVID-19, along with the clinical lab results of the patients hospitalized. In comparison with different ML models such as Logistic Regression, Support Vector Machine (SVM), XGBoost and Artificial Neural Network (ANN) to predict and classify the patients as Long COVID or Short COVID during the first week of COVID-19, ANN has outperformed the other models with an accuracy of 81% when considering the symptoms of COVID-19 and a 79% for the clinical test data. The predictive factors and the significant clinical tests for the Long COVID are also determined by using different methods like Chi-square Test and Pearson Correlation.

Source: S. S. Parvathy, Nagesh Subbanna, Sethuraman Rao, Rahul Krishnan Pathinarupothi, T. S. Dipu, Merlin Moni, Chithira V. Nair; Data-driven prognosis of long COVID in patients using machine learning. AIP Conf. Proc. 15 December 2023; 2901 (1): 060014. https://doi.org/10.1063/5.0178561 https://pubs.aip.org/aip/acp/article/2901/1/060014/2930006 (Full text available as PDF file)