Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis

Abstract:

Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19’s long-term effects at 12 months and above.

We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976.

At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.

Source: Mudgal S K, Gaur R, Rulaniya S, et al. (March 18, 2023) Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis. Cureus 15(3): e36325. doi:10.7759/cureus.36325 https://www.cureus.com/articles/143288-pooled-prevalence-of-long-covid-19-symptoms-at-12-months-and-above-follow-up-period-a-systematic-review-and-meta-analysis#!/ (Full text)

A Review of Possible Supplements to Relieve the Symptoms of Fatigue after COVID-19

Abstract:

Background: The highly infectious coronavirus has become a global pandemic; the effective medication is yet to be developed. The health care system was strained; millions of people have been suffered from infection and complications. Post COVID-19 fatigue is a dominant characteristic of coronavirus infection. It affects general state of health, muscle strength, sleeping quality, mental health, and life quality. This paper is emphasizing and summarizing the potential beneficial supplementations of post COVID-19 fatigue symptoms.

Methods: The knowledge gained from PubMed and from the National Library of Medicine. Clinical studies and systematic review articles were collected in this topic.

Results: Herein, we discuss the possible therapeutic supplementations with anti-inflammatory, immunomodulatory and antioxidant effect. Vitamin complexes, trace elements, antioxidants, coenzymes, probiotics, essential fatty acids; one and creatine as amino acid derivatives have been appeared to be effective in relieving post COVID-19 fatigue symptoms.

Conclusions: Based on the data, these nutrients and supplements might be important to alleviate the post COVID-19 fatigue symptoms and they could be considered as a supportive therapy

Source: Boglárka Bernadett Tisza, Gyöngyi Iván, Viola Keczeli, Melinda Kóró, Patricia Szántóri, Zsófia Gyócsiné Varga, Henriett Müller, Olivia Pribéli, Zoltán Szabó, Zsófia Verzár, Monika Sélleyné Gyuró, Andrea Gubicskóné Kisbendek and Tímea Stromájer-Rácz. A Review of Possible Supplements to Relieve the Symptoms of Fatigue after COVID-19.  J Med Public Health. 2023;4(2):JMPH-04-1062. https://www.medtextpublications.com/open-access/a-review-of-possible-supplements-to-relieve-the-symptoms-of-1309.pdf (Full text)

The prevalence of stigma in a UK community survey of people with lived experience of long COVID

Abstract:

Background: Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, health-related, behavioural, or other attributes deemed to be undesirable. Long COVID is a predominantly multisystem condition that occurs in people with a history of SARS-CoV-2 infection, often resulting in functional disability, which limits day-to-day activities. We aimed to quantify the burden of stigma experienced in a community-based sample of people with lived experience of long COVID.

Methods: Data from the follow-up of a long COVID longitudinal online survey was used. The survey was coproduced with people living with long COVID. 13 questions on stigma were included to develop a Long COVID Stigma Scale capturing three domains: enacted (overt experiences of discrimination due to long COVID), internalised (internalising negative associations with long COVID and accepting them as self-applicable), and anticipated (expectation of bias or poor treatment by others) stigma. Data were collected through a social media survey with convenience non-probability sampling.

Findings: 966 (47·9%) of 2016 participants from the UK completed the follow-up survey and 888 responded to the questions on stigma. The mean age of respondents was 48·3 years (SD 10·7), and 84·6% identified as female. Roughly half (n=460, 50·4%) reported having a formal, clinical, long COVID diagnosis, and of these, 440 responded to the questions on stigma. The prevalence of people experiencing overall stigma at least sometimes was 95·4% (n=847), prevalence of enacted stigma was 62·7% (n=557), internalised stigma was 86·4% (n=767), and anticipated stigma was 90·8% (n=806). Prevalence of stigma was higher in respondents with a formal diagnosis of long COVID (97·5%; n=429) than in those without (93·2%; n=413).

Interpretation: This study highlights widespread and multilayered stigmas experienced by people living with long COVID in the UK, which presents a serious public health concern. The broader literature on stigmatised health conditions consistently suggests that stigma drives people away from health services, contributes to psychological distress, and compromises long-term physical outcomes. The higher proportion experiencing stigma in those with clinical diagnosis of long COVID might be indicative of stigma within the health-care system. Findings from this study should be taken into consideration within clinical practice and health care, social care, employment, and education policies.

Source: Pantelic M, Ziauddeen N, Boyes M, O’Hara ME, Hastie C, Alwan NA. The prevalence of stigma in a UK community survey of people with lived experience of long COVID. Lancet. 2022 Nov;400 Suppl 1:S84. doi: 10.1016/S0140-6736(22)02294-2. Epub 2022 Nov 24. PMID: 36930033. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02294-2/fulltext

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 TuftsDawit T ZemedikunAnuradhaa SubramanianNaijie GuanKrishna GokhalePuja MylesTim WilliamsTom Marshall, Melanie Calvert, Karen MatthewsKrishnarajah NirantharakumarLouise JacksonShamil Haroon. The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data.

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)