Category: Overlapping Illnesses

The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data

Abstract:

Objectives To assess incremental costs of primary care consultations associated with post-Covid-19 condition or long COVID, to estimate associated national costs for the United Kingdom population, and to assess risk factors associated with increased costs.

Design A retrospective cohort study using a propensity score matching approach with an incremental cost method to estimate primary care consultation costs associated with long COVID.

Setting UK based primary care general practitioner (GP), nurse and physiotherapist consultation data from the Clinical Practice Research Datalink Aurum primary care database from 31st January 2020 to 15th April 2021.

Participants 472,173 non-hospitalised adults with confirmed SARS-CoV-2 infection were 1:1 propensity score matched to a pool of eligible patients with the same index date, the same number of prior consultations, and similar background characteristics, but without a record of COVID-19. Patients diagnosed with Long COVID (3,871) and those with World Health Organisation (WHO) defined symptoms of long COVID (30,174) formed two subgroups within the cohort with confirmed SARS-CoV-2 infection.

Main outcome measures Costs were calculated using a bottom-up costing approach with consultation cost per working hour in pound sterling (£) obtained from the Personal Social Services Research Unit’s Unit Costs of Health and Social Care 2021. The average incremental cost in comparison to patients with no record of COVID-19 was produced for each patient group, considering only consultation costs at least 12 weeks from the SARS-CoV-2 infection date or matched date for the comparator group (from 15th April 2020 to 15th April 2021). A sensitivity analysis was undertaken which restricted the study population to only those who had at least 24 weeks of follow-up. National costs were estimated by extrapolating incremental costs to the cumulative incidence of COVID-19 in the UK Office for National Statistics COVID-19 Infection Survey. The impacts of risk factors on the cost of consultations beyond 12 weeks from SARS-CoV-2 infection were assessed using an econometric ordinary least squares (OLS) regression model, where coefficients were interpreted as the percentage change in cost due to a unit increase in the specific factor.

Results The incremental cost of primary care consultations potentially associated with long COVID was £2.44 per patient with COVID-19 per year. This increased to £5.72 in the sensitivity analysis. Extrapolating this to the UK population produced a cost estimate of £23,382,452 (90% credible interval: £21,378,567 to £25,526,052) or £54,814,601 (90% credible interval: £50,116,967 to £59,839,762) in the sensitivity analysis. Among patients with COVID-19 infection, a long COVID diagnosis and longer-term reporting of symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age (49% relative increase in costs in those aged 80 years or older compared to those aged 18 to 29 years), female sex (4% relative increase in costs compared to males), obesity (4% relative increase in costs compared to those of normal weight), comorbidities and the number of prior consultations were all associated with an increase in the cost of primary care consultations. By contrast, those from black ethnic groups had a 6% reduced relative cost compared to those from white ethnic groups.

Conclusions The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.

What is already known on this topic?

  • Long COVID is a global public health challenge, with millions of people affected worldwide.

  • People with a history of long COVID use health services, including primary care, at a higher rate than uninfected individuals even beyond the period of acute infection.

  • The cost of this increased healthcare use is unknown, impeding planning and forecasting of resource requirements needed to adequately support people with long COVID.

What this study adds?

  • Beyond 12 weeks from acute infection, non-hospitalised adults with a history of SARS-CoV-2 infection cost primary care services an additional £2.44 per patient per year greater on average than patients with no prior evidence of infection.

  • Due to the high incidence of COVID-19, this represents a substantial cost to primary care services, in the UK exceeding £20 million for consultations associated with long COVID.

  • These incremental costs are greater in those with a formal diagnosis of long COVID, those reporting related symptoms, older adults, females, and those with obesity.

Source: Jake Tufts, Dawit T Zemedikun,  Anuradhaa Subramanian,  Naijie Guan,  Krishna Gokhale,  Puja Myles,  Tim Williams,  Tom Marshall, Melanie Calvert, Karen Matthews, Krishnarajah Nirantharakumar, Louise Jackson, Shamil Haroon. The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data. medRxiv 2023.03.12.23287049; doi: https://doi.org/10.1101/2023.03.12.23287049 https://www.medrxiv.org/content/10.1101/2023.03.12.23287049v1.full-text

Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis

Abstract:

The question of COVID-19 and long-COVID-19 course in children remains unsolved. This infection in children, which is associated with COVID-19, can vary from asymptomatic to systemic damage of various systems. Multisystem inflammatory syndrome in children, associated with SARS-CoV-2 (MIS-C), is a serious condition in children and adolescents after experiencing COVID-19.
Published data on MIS-C have indicated that the inflammation can be registered in the gastrointestinal tract (60–100%), as well as in cardiovascular (80%), nervous (29–58%), and respiratory (21–65%) systems. However, with the changing characteristics of SARS-CoV-2, the manifestations of COVID-19 and long-COVID-19 in children have also been changing. Currently, there is no clear understanding of the development of severe COVID-19 and MIS-C in children, especially after being exposed to patients with COVID-19.
We presented two new clinical courses of multisystem inflammatory syndrome in children with severe multisystem damage after close contact to relatives with COVID-19 or long-COVID-19. Thus, high-risk children, who are positive for SARS-CoV-2 infection after contact with COVID-19 patients, should be clinically managed during the first few months. The identification of the disease complexity requires the involvement of neurologists, cardiologists, and other specialists.
Source: Vasichkina E, Kofeynikova O, Fetisova S, Starshinova AY, Sheyanova E, Vershinina T, Ryzhkov A, Skripnik A, Alekseeva D, Nechaeva E, Glushkova A, Kudlay D, Pervunina T, Starshinova A. Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis. Life. 2023; 13(3):781. https://doi.org/10.3390/life13030781 https://www.mdpi.com/2075-1729/13/3/781 (Full text)

Nutritional deficiencies that may predispose to long COVID

Abstract:

Multiple nutritional deficiencies (MND) confound studies designed to assess the role of a single nutrient in contributing to the initiation and progression of disease states. Despite the perception of many healthcare practitioners, up to 25% of Americans are deficient in five-or-more essential nutrients. Stress associated with the COVID-19 pandemic further increases the prevalence of deficiency states. Viral infections compete for crucial nutrients with immune cells. Viral replication and proliferation of immunocompetent cells critical to the host response require these essential nutrients, including zinc. Clinical studies have linked levels of more than 22 different dietary components to the likelihood of COVID-19 infection and the severity of the disease. People at higher risk of infection due to MND are also more likely to have long-term sequelae, known as Long COVID.

Source: Schloss, J.V. Nutritional deficiencies that may predispose to long COVID. Inflammopharmacol (2023). https://doi.org/10.1007/s10787-023-01183-3 https://link.springer.com/article/10.1007/s10787-023-01183-3 (Full text)

A Case Study of Successful Application of the Principles of ME/CFS Care to an Individual with Long COVID

Abstract:

Persistent fatigue is one of the most common symptoms of post-COVID conditions, also termed long COVID. At the extreme end of the severity spectrum, some individuals with long COVID also meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), raising the possibility that symptom management approaches for ME/CFS may benefit some long COVID patients.

We describe the long-term outcomes of a 19-year-old male who developed profound impairment consistent with ME/CFS after a SARS-CoV-2 infection early in the pandemic.

We evaluated and treated him using our clinic’s approach to ME/CFS. This included a history and physical examination that ascertained joint hypermobility, pathological reflexes, physical therapy maneuvers to look for a range of motion restrictions in the limbs and spine, orthostatic testing, and screening laboratory studies.

He was found to have profound postural tachycardia syndrome, several ranges of motion restrictions, and mast cell activation syndrome. He was treated according to our clinic’s guidelines for managing ME/CFS, which included manual physical therapy maneuvers and both non-pharmacologic measures and medications directed at postural tachycardia syndrome and mast cell activation.

He experienced significant improvement in his symptoms over 30 months. His case emphasizes how the application of the principles of treating ME/CFS has the potential to provide a direction for treating long COVID.

Source: Petracek LS, Broussard CA, Swope RL, Rowe PC. A Case Study of Successful Application of the Principles of ME/CFS Care to an Individual with Long COVID. Healthcare. 2023; 11(6):865. https://doi.org/10.3390/healthcare11060865 (Full text)

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series

Abstract:

Introduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

Materials and methods: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers.

Results: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%).

Conclusion: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Source: Bocci T, Bertini A, Campiglio L, Botta S, Libelli G, Guidetti M, Priori A. Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series. Neurol Sci. 2023 Apr;44(4):1147-1153. doi: 10.1007/s10072-023-06637-8. Epub 2023 Feb 3. PMID: 36735149; PMCID: PMC9896447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896447/ (Full study)

Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program

Abstract:

Objectives: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.

Materials and methods: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls.

Results: We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise.

Discussion: Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes.

Conclusion: We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.

Source: Lorman V, Rao S, Jhaveri R, Case A, Mejias A, Pajor NM, Patel P, Thacker D, Bose-Brill S, Block J, Hanley PC, Prahalad P, Chen Y, Forrest CB, Bailey LC, Lee GM, Razzaghi H. Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program. JAMIA Open. 2023 Mar 14;6(1):ooad016. doi: 10.1093/jamiaopen/ooad016. PMID: 36926600; PMCID: PMC10013630. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013630/ (Full text)

Pain Management in the Post-COVID Era-An Update: A Narrative Review

Abstract:

An extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is demonstrated, the term “long-COVID” is used.

Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches.

All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID.

Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on the patients, health care systems, and society as well. Therefore, it is important that patients with chronic pain receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description about the post-COVID pain and to explore the impact of long COVID-19 on chronic pain patients, and also to give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.

Source: El-Tallawy SN, Perglozzi JV, Ahmed RS, Kaki AM, Nagiub MS, LeQuang JK, Hadarah MM. Pain Management in the Post-COVID Era-An Update: A Narrative Review. Pain Ther. 2023 Apr;12(2):423-448. doi: 10.1007/s40122-023-00486-1. Epub 2023 Feb 28. PMID: 36853484; PMCID: PMC9971680. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971680/ (Full text)

Epidemiological and clinical perspectives of long COVID syndrome

Abstract:

Long COVID, or post-acute COVID-19 syndrome, is characterized by multi-organ symptoms lasting 2+ months after initial COVID-19 virus infection. This review presents the current state of evidence for long COVID syndrome, including the global public health context, incidence, prevalence, cardiopulmonary sequelae, physical and mental symptoms, recovery time, prognosis, risk factors, rehospitalization rates, and the impact of vaccination on long COVID outcomes. Results are presented by clinically relevant subgroups.

Overall, 10-35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic stress disorder, memory loss, and difficulty concentrating. Delineating these issues will be crucial to inform appropriate post-pandemic health policy and protect the health of COVID-19 survivors, including potentially vulnerable or underrepresented groups. Directed to policymakers, health practitioners, and the general public, we provide recommendations and suggest avenues for future research with the larger goal of reducing harms associated with long COVID syndrome.

Source: Huerne K, Filion KB, Grad R, Ernst P, Gershon AS, Eisenberg MJ. Epidemiological and clinical perspectives of long COVID syndrome. Am J Med Open. 2023 Jun;9:100033. doi: 10.1016/j.ajmo.2023.100033. Epub 2023 Jan 18. PMID: 36685609; PMCID: PMC9846887. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846887/ (Full text)

Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection?

Abstract:

Patients recovered from a COVID-19 infection often report vague symptoms of fatigue or dyspnoea, comparable to the manifestations in patients with central sensitisation. The hypothesis was that central sensitisation could be the underlying common aetiology in both patient populations. This study explored the presence of symptoms of central sensitisation, and the association with functional status and health-related quality of life, in patients post COVID-19 infection.

Patients who were previously infected with COVID-19 filled out the Central Sensitisation Inventory (CSI), the Post-COVID-19 Functional Status (PCFS) Scale and the EuroQol with five dimensions, through an online survey. Eventually, 567 persons completed the survey. In total, 29.73% of the persons had a score of <40/100 on the CSI and 70.26% had a score of ≥40/100. Regarding functional status, 7.34% had no functional limitations, 9.13% had negligible functional limitations, 37.30% reported slight functional limitations, 42.86% indicated moderate functional limitations and 3.37% reported severe functional limitations.

Based on a one-way ANOVA test, there was a significant effect of PCFS Scale group level on the total CSI score (F(4,486) = 46.17, p < 0.001). This survey indicated the presence of symptoms of central sensitisation in more than 70% of patients post COVID-19 infection, suggesting towards the need for patient education and multimodal rehabilitation, to target nociplastic pain.

Source: Goudman L, De Smedt A, Noppen M, Moens M. Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection? J Clin Med. 2021 Nov 28;10(23):5594. doi: 10.3390/jcm10235594. PMID: 34884296; PMCID: PMC8658135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658135/ (Full text)

Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review

Summary:

Many of the people that get infected with the Coronavirus develop long-lasting complaints and are diagnosed with Long COVID after the acute infection is gone. These complains can last several months or years and include fatigue, cognitive impairment, sleeping problems and post-exertional symptom exacerbation (PESE). Research shows that COVID-19 patients with an acute infection have abnormalities in their brain, which could potentially lead to long-lasting neurological problems and symptoms. However, although many researchers are trying to uncover the underlying mechanisms, Long COVID is still very new.
The underlying mechanisms causing and maintaining the disease are therefore unclear. A large group of Long COVID patients resembles patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in terms of symptoms and, in many cases, the viral trigger of the disease. A core symptom of ME/CFS is PESE, which is uncommon in other fatiguing illnesses, but frequently seen in Long COVID patients. PESE involves an abnormal worsening of symptoms and cognitive and physical functions after any type of normal activity. Because of the large symptom overlap and lack of knowledge regarding PESE, underlying brain-mechanisms associated with Long COVID and ME/CFS in general as well as after physical exertion were investigated.
The findings of this review indicate that ME/CFS is associated with several abnormalities in the brain which are also proposed to be present in Long COVID patients. Such abnormalities include inflammation of the brain, shrinkage of the brain and less blood flow to the brain. After physical exertion, these abnormalities might be exacerbated in ME/CFS patients. This results in a brain that needs to work harder than the healthy brain to complete a task. It is demonstrated by increased brain activity in several brain regions after physical exertion and general symptom exacerbation. Since the two diseases seem to have a large overlap in symptoms and underlying brain-mechanisms, this finding might apply to patients with long COVID as well. Importantly, Long COVID seems to consist of different subgroups of which a large part fulfills the criteria for ME/CFS.
Treatment and therapy for ME/CFS patients is therefore likely transferable to this subgroup of Long COVID patients, with explicit attention towards the PESE phenomenon. More research is needed to uncover the underlying mechanisms as well as correct treatment approach of these diseases. Future research should take subgroups of Long COVID into account.
Source: Rodenburg, Sanne. Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review. Master Thesis, Utrecht University. March 14, 2023. https://studenttheses.uu.nl/bitstream/handle/20.500.12932/43647/Rodenburg_7433050_Neuropathology%20and%20neurological%20manifestations%20in%20MECFS%20and%20Long%20COVID%20with%20focus%20on%20PESE.pdf (Full text)