An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond)

Abstract:

Objectives: Some people do not fully recover from an acute viral infection and experience persistent symptoms or incomplete recovery for months or even years. This is not unique to the SARS-CoV-2 virus and history shows that post-viral conditions like post COVID-19 condition, also referred to as Long Covid, are not new. In particular, during and after pandemics caused by respiratory viruses in which large parts of the population were infected or exposed, professional and public attention was increased, not least because of the large number of people affected.

Methods: Given the current relevance of the topic, this article aims to narratively review and summarize the literature on post-viral symptoms during past pandemics and to supplement and illustrate it with Swiss examples from the pandemics of 1890, 1918–1920 and later.

Results: Post-viral diseases were an increasingly emphasised health topic during and after past pandemics triggered by respiratory infections over the last 150 years.

Conclusion: In the next pandemic, it should not be surprising that post-viral conditions will again play a role, and pandemic plans should reflect this.

Source: Staub, Kaspar; Ballouz, Tala; Puhan, Milo (2024). An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond). Public Health Reviews, 45:1606966. https://www.ssph-journal.org/articles/10.3389/phrs.2024.1606966/full (Full text)

How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review

Abstract:

Background: Post Coronavirus disease (COVID) and other post-viral infection syndromes present an overlap of pathogenesis, onset, progression, and symptom profile. We aimed to systematically describe studies on post-viral conditions and determine the entity of post COVID compared to other post-viral conditions in children.

Methods: We conducted a systematic search of the Embase, MEDLINE, Cochrane Library, and GoogleScholar databases (January 1946-3 November 2023), according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The main outcomes were differences in condition duration, symptom type, and development of chronic symptoms. This systematic review was registered on PROSPERO (CRD42023401789).

Findings: 35/5051 studies were included, with 42,934 children, adolescents and young adults (0-20 years old) overall. Twenty-eight studies focused on post COVID symptoms, followed by five papers on Respiratory Syncytial Virus (RSV) and Rhinovirus, one study on Epstein-Barr Virus (EBV), and one on gastrointestinal viruses. Studies on post COVID mainly reported data on older children/adolescents, describing long-lasting symptoms, including fatigue, neurologic, cardiorespiratory, musculoskeletal, mental health, and gastrointestinal symptoms. The maximum described symptoms duration was eighteen months, with an average follow-up of seven months. The development of chronic symptoms was reported by 30 studies (93.8%) for 10,473/28,474 patients (36.8%). Recovery was achieved in 18,001/28,474 cases (63.2%). The study on EBV reported persistent fatigue in adolescents for a similar duration (6 months, 46% chronic). Studies on RSV and Rhinovirus were mainly done in children under three years, with development of recurrent wheezing (up to 3 years).

Interpretation: Post-viral fatigue was a shared feature between post COVID and post EBV conditions. A better understanding of post COVID as a unique condition, sharing features with other post-viral syndromes, is needed. The healthcare burden and socio-economic consequences for children and their families warrant further investigation and development of appropriate healthcare management plans. The foremost requirement is the establishment of consistent and shareable definitions, as well as a consensus on outcomes, to effectively evaluate follow-up and quantify the burden of different viral infections.

Source: Minotti C, McKenzie C, Dewandel I, Bekker C, Sturniolo G, Doni D, Giaquinto C, Van Der Zalm MM, Donà D. How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review. EClinicalMedicine. 2024 Feb 2;68:102436. doi: 10.1016/j.eclinm.2024.102436. PMID: 38333536; PMCID: PMC10850405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10850405/ (Full text)

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Abstract:

Background: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.

Methods: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections’ contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).

Results: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a “moderate association” by Cohen’s d test) compared to both healthy and diseased controls.

Conclusion: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Source: Hwang, JH., Lee, JS., Oh, HM. et al. Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis. J Transl Med 21, 763 (2023). https://doi.org/10.1186/s12967-023-04635-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04635-0 (Full text)

Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept

Abstract:

Background: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.

Methods: Summary of the current literature and presentation of clinical characteristics as well as presentation of a model project for a multimodal pain therapy in postviral syndromes with PEM.

Model concept: The presented model project describes a day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.

Source: Luchting B, Behrends U, Eigner B, Stojanov S, Warlitz C, Haegele M, Neuwirth E, Mihatsch L, Richter HP. Interdisziplinäre multimodale Schmerztherapie bei postviralen Syndromen und ME/CFS : Besonderheiten, Fallstricke und Modellkonzept [Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept]. Schmerz. 2023 Oct 20. German. doi: 10.1007/s00482-023-00761-2. Epub ahead of print. PMID: 37 https://pubmed.ncbi.nlm.nih.gov/37864020/864020.

Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies

Summary:

In this Personal View, we discuss current knowledge on SARS-CoV-2 RNA or antigen persistence in children infected with SARS-CoV-2. Based on the evidence that the virus can persist in adults, we have done a literature review and analysed studies that looked for SARS-CoV-2 RNA or antigens in children undergoing autopsy, biopsy, or surgery for either death from COVID-19 or multisystem inflammatory syndrome, or assessments for long COVID-19 or other conditions.
Our analysis suggests that in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months. We discuss what is known about the biological effects of viral persistence for other viral infections and highlight new scenarios for clinical, pharmacological, and basic research exploration. Such an approach will improve the understanding and management of post-viral syndromes.
Source: Danilo Buonsenso, Laura Martino, Rosa Morello, Francesco Mariani, Kelly Fearnley, Piero . Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies. The Lancet Microbe. Published: June 26, 2023. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(23)00115-5/fulltext (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)

Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases

Abstract:

Historically, COVID-19 emerges as one of the most devastating diseases of humankind, which creates an unmanageable health crisis worldwide. Until now, this disease costs millions of lives and continues to paralyze human civilization’s economy and social growth, leaving an enduring damage that will take an exceptionally long time to repair.

While a majority of infected patients survive after mild to moderate reactions after two to six weeks, a growing population of patients suffers for months with severe and prolonged symptoms of fatigue, depression, and anxiety. These patients are no less than 10% of total COVID-19 infected individuals with distinctive chronic clinical symptomatology, collectively termed post-acute sequelae of COVID-19 (PASC) or more commonly long-haul COVID. Interestingly, Long-haul COVID and many debilitating viral diseases display a similar range of clinical symptoms of muscle fatigue, dizziness, depression, and chronic inflammation.

In our current hypothesis-driven review article, we attempt to discuss the molecular mechanism of muscle fatigue in long-haul COVID, and other viral diseases as caused by HHV6, Powassan, Epstein-Barr virus (EBV), and HIV. We also discuss the pathological resemblance of virus-triggered muscle fatigue with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Source: Gottschalk CG, Peterson D, Armstrong J, Knox K, Roy A. Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases. Infect Agent Cancer. 2023 Feb 7;18(1):7. doi: 10.1186/s13027-023-00485-z. PMID: 36750846; PMCID: PMC9902840. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902840/ (Full text)

COVID-Specific Long-Term Sequelae in Comparison to Common Viral Respiratory Infections: An Analysis of 17,487 Infected Adult Patients

Abstract:
Background: Better understanding of long-term health effects after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become one of the healthcare priorities in the current pandemic. We analyzed large and diverse patient cohort to study health effects related to SARS-CoV-2 infection occurring more than one month post-infection.
Methods: We analyzed 17,487 patients who received diagnoses for SARS-CoV-2 infection in a total of 122 healthcare facilities in the United States prior to April, 14,2022. Patients were propensity score matched with patients diagnosed with the common cold, influenza, or viral pneumonia from March 1, 2020, to April 1, 2021. For each outcome, SARS-CoV-2 was compared to a generic Viral Respiratory Infection (VRI) by predicting diagnoses in the period between 30 and 365 days post-infection. Both COVID-19 and VRI patients were propensity score matched with patients with no record of COVID-19 or VRI and the same methodology was applied. Diagnoses where COVID-19 infection was a significant positive predictor in both COVID-19 vs VRI and COVID-19 vs Control comparisons were considered COVID-19-specific effects.
Results: Compared to common VRIs, SARS-CoV-2 was associated with diagnoses palpitations, hair loss, fatigue, chest pain, dyspnea, joint pain, and obesity in the post-infectious period.
Conclusions: We identify that some diagnoses commonly described as “long COVID” do not appear significantly more frequent post-COVID-19 infection compared to other common VRIs. We also identify sequelae which are specifically associated with a prior SARS-CoV-2 infection.
Source: William I Baskett, MS, Adnan I Qureshi, MD, Daniel Shyu, MD, Jane M Armer, PhD, RN, Chi-Ren Shyu, PhD, COVID-Specific Long-Term Sequelae in Comparison to Common Viral Respiratory Infections: An Analysis of 17,487 Infected Adult Patients, Open Forum Infectious Diseases, 2022;, ofac683, https://doi.org/10.1093/ofid/ofac683 (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)

Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Background: As complaints of long-haul COVID patients are similar to those of ME/CFS patients and as orthostatic intolerance (OI) plays an important role in the COVID infection symptomatology, we compared 14 long-haul COVID patients with 14 ME/CFS patients with a post-viral Ebstein-Barr (EBV) onset and 14 ME/CFS patients with an insidious onset of the disease.
Methods: In all patients, OI analysis by history taking and OI assessed during a tilt test, as well as cerebral blood flow measurements by extracranial Doppler, and cardiac index measurements by suprasternal Doppler during the tilt test were obtained in all patients.
Results: Except for disease duration no differences were found in clinical characteristics. The prevalence of POTS was higher in the long-haul patients (100%) than in post-EBV (43%) and in insidious-onset (50%) patients (p = 0.0002). No differences between the three groups were present in the prevalence of OI, heart rate and blood pressure changes, changes in cerebral blood flow or in cardiac index during the tilt test.
Conclusion: OI symptomatology and objective abnormalities of OI (abnormal cerebral blood flow and cardiac index reduction during tilt testing) are comparable to those in ME/CFS patients. It indicates that long-haul COVID is essentially the same disease as ME/CFS.
Source: van Campen CMC, Visser FC. Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare. 2022; 10(10):2058. https://doi.org/10.3390/healthcare10102058 (Full text)