Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data

Abstract:

Whilst the entire world is battling the second wave of COVID-19, a substantial proportion of patients who have suffered from the condition in the past months are reporting symptoms that last for months after recovery, i. e., long-term COVID-19 symptoms. We aimed to assess the current evidence on the long-term symptoms in COVID-19 patients. We did a systematic review on PubMed, Web of Science, EMBASE, and Google Scholar from database inception to February 15, 2021, for studies on long-term COVID-19 symptoms.

We included all type of papers that reported at least one long-term COVID-19 symptom. We screened studies using a standardized data collection form and pooled data from published studies. Cohort cross-sectional, case-report, cases-series, case-control studies, and review were graded using specific quality assessment tools. Of 11,361 publications found following our initial search we assessed 218 full-text articles, of which 145 met all selection criteria. We found that 20.70% of reports on long-term COVID-19 symptoms were on abnormal lung functions, 24.13% on neurologic complaints and olfactory dysfunctions, and 55.17% on specific widespread symptoms, mainly chronic fatigue, and pain.

Despite the relatively high heterogeneity of the reviewed studies, our findings highlighted that a noteworthy proportion of patients who have suffered from SARS-CoV-2 infection present a “post-COVID syndrome.” The multifaceted understanding of all aspects of the COVID-19 pandemic, including these long-term symptoms, will allow us to respond to all the global health challenges, thus paving the way to a stronger public health.

Source: Salamanna F, Veronesi F, Martini L, Landini MP, Fini M. Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data. Front Med (Lausanne). 2021 May 4;8:653516. doi: 10.3389/fmed.2021.653516. PMID: 34017846; PMCID: PMC8129035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129035/ (Full text)

Editorial: The Pathogenesis of Long-Term Neuropsychiatric COVID-19 and the Role of Microglia, Mitochondria, and Persistent Neuroinflammation: A Hypothesis

Abstract:

Persistent comorbidities occur in patients who initially recover from acute coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ‘Long COVID’ involves the central nervous system (CNS), resulting in neuropsychiatric symptoms and signs, including cognitive impairment or ‘brain fog’ and chronic fatigue syndrome. There are similarities in these persistent complications between SARS-CoV-2 and the Ebola, Zika, and influenza A viruses. Normal CNS neuronal mitochondrial function requires high oxygen levels for oxidative phosphorylation and ATP production. Recent studies have shown that the SARS-CoV-2 virus can hijack mitochondrial function. Persistent changes in cognitive functioning have also been reported with other viral infections. SARS-CoV-2 infection may result in long-term effects on immune processes within the CNS by causing microglial dysfunction. This short opinion aims to discuss the hypothesis that the pathogenesis of long-term neuropsychiatric COVID-19 involves microglia, mitochondria, and persistent neuroinflammation.

Source: Stefano GB, Büttiker P, Weissenberger S, Martin A, Ptacek R, Kream RM. Editorial: The Pathogenesis of Long-Term Neuropsychiatric COVID-19 and the Role of Microglia, Mitochondria, and Persistent Neuroinflammation: A Hypothesis. Med Sci Monit. 2021 May 10;27:e933015. doi: 10.12659/MSM.933015. PMID: 34016942. https://pubmed.ncbi.nlm.nih.gov/34016942/

COVID-19 symptoms over time: comparing long-haulers to ME/CFS

Abstract:

Introduction: Our objective was to determine which symptoms among long-hauler COVID-19 patients change over time, and how their symptoms compare to another chronic illness group.

Methods: 278 long-haulers completed two symptom questionnaires at one time point, with one recounting experiences during the first two weeks of their illness, an average of 21.7 weeks prior. We used a comparison group of 502 patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Participants completed a standardized symptom questionnaire and a list of additional CDC COVID-19 symptoms.

Results: Over time, the long-haulers reported an overall reduction of most symptoms including unrefreshing sleep and post-exertional malaise, but an intensification of neurocognitive symptoms. When compared to ME/CFS, the COVID-19 sample was initially more symptomatic for the immune and orthostatic domains but over time, the long-haulers evidenced significantly less severe symptoms than those with ME/CFS, except in the orthostatic domain. Among the COVID-19 long haulers, several neurocognitive symptoms got worse over time, whereas improvements occurred in most other areas.

Conclusions: These types of differential patterns of symptoms over time might contribute to helping better understand the pathophysiology of those reporting prolonged illness following COVID-19.

Source: Leonard A. Jason, Mohammed F. Islam, Karl Conroy, Joseph Cotler, Chelsea Torres, Mady Johnson & Brianna Mabie (2021) COVID-19 symptoms over time: comparing long-haulers to ME/CFS, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2021.1922140 https://www.tandfonline.com/doi/full/10.1080/21641846.2021.1922140

Undetected Jawbone Marrow Defects as Inflammatory and Degenerative Signaling Pathways: Chemokine RANTES/CCL5 as a Possible Link Between the Jawbone and Systemic Interactions?

Abstract:

Background: Cytokines, especially chemokines, are of increasing interest in immunology. This study characterizes the little-known phenomenon of “bone marrow defects of the jawbone” (BMDJ) with known overexpression of the chemokine RANTES/CCL5 (R/C).

Purpose: Our investigation clarifies why BMDJ and the intensity of local R/C overexpression are challenging to detect, as examined in patients with seven different systemic immunological diseases. Specifically, we investigate whether R/C overexpression is specific to certain disease groups or if it represents a type of signal disruption found in all systemic immunological diseases.

Patients and Methods: In a total of 301 patients, BMDJ was surgically repaired during clinical practice to reduce “silent inflammation” associated with the presence of jaw-related pathologies. In each case of BMDJ, bone density was measured preoperatively (in Hounsfield units [HU]), while R/C expression was measured postoperatively. Each of the 301 patients suffered from allergies, atypical facial and trigeminal pain, or were diagnosed with neurodegenerative diseases, tumors, rheumatism, chronic fatigue syndrome, or parasympathetic disorders.

Results: In all BMDJ cases, strongly negative HU values indicated decreased bone density or osteolysis. Consistently, all cases of BMDJ showed elevated R/C expression. These findings were consistently observed in every disease group.

Discussion: BMDJ was confirmed in all patients, as verified by the HU measurements and laboratory results related to R/C expression. The hypothesis that a specific subset of the seven disease groups could be distinguished either based on the increased presence of BMDJ and by the overexpression of R/C could not be confirmed. A brief literature review confirms the importance of R/C in the etiology of each of the seven disease groups.

Conclusion: In this research, the crucial role played by BMDJ and the chemokine R/C in inflammatory and immune diseases is discussed for seven groups of patients. Each specific immune disease can be influenced or propelled by BMDJ-derived R/C inflammatory signaling pathways.

Source: Lechner J, Schmidt M, von Baehr V, Schick F. Undetected Jawbone Marrow Defects as Inflammatory and Degenerative Signaling Pathways: Chemokine RANTES/CCL5 as a Possible Link Between the Jawbone and Systemic Interactions? J Inflamm Res. 2021 Apr 21;14:1603-1612. doi: 10.2147/JIR.S307635. PMID: 33911892; PMCID: PMC8071694.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071694/ (Full text)

Humility and Acceptance: Working Within Our Limits With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Synopsis:
The term long COVID was coined by patients to describe the long-term consequences of COVID-19. One year into the pandemic, it was clear that all patients—those hospitalized with COVID-19 and those who lived with the disease in the community—were at risk of developing debilitating sequelae that would impact their quality of life. Patients with long COVID asked for rehabilitation. Many of them, including previously healthy and fit clinicians, tried to fight postviral fatigue with exercise-based rehabilitation. We observed a growing number of patients with long COVID who experienced adverse effects from exercise therapy and symptoms strikingly similar to those of myalgic encephalomyelitis (ME). Community-based physical therapists, including those in private practice, unaware of safety issues, are preparing to help an influx of patients with long COVID. In this editorial, we expose growing concerns about long COVID and ME. We issue safety recommendations for rehabilitation and share resources to improve care for those with postviral illnesses. J Orthop Sports Phys Ther 2021;51(5):197–200. doi:10.2519/jospt.2021.0106

Source: Simon DécaryIsabelle GabourySabrina PoirierChristiane GarciaScott SimpsonMichelle BullDarren Brown, and Frédérique Daigle. Humility and Acceptance: Working Within Our Limits With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Orthopaedic & Sports Physical Therapy 2021 51:5197-200. https://www.jospt.org/doi/10.2519/jospt.2021.0106

Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology

Abstract:

Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions.

Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology.

Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study.

Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.

Source: Wong TL, Weitzer DJ. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas). 2021 Apr 26;57(5):418. doi: 10.3390/medicina57050418. PMID: 33925784.  https://pubmed.ncbi.nlm.nih.gov/33925784/

Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue

Abstract:

COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

Source: Theoharides TC, Cholevas C, Polyzoidis K, Politis A. Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue. Biofactors. 2021 Apr 12. doi: 10.1002/biof.1726. Epub ahead of print. PMID: 33847020. https://pubmed.ncbi.nlm.nih.gov/33847020/

How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight

Abstract:

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

Source: Kuo CF, Shi L, Lin CL, Yao WC, Chen HT, Lio CF, Wang YT, Su CH, Hsu NW, Tsai SY. How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight. Sci Rep. 2021 Apr 6;11(1):7520. doi: 10.1038/s41598-021-87018-z. PMID: 33824394. https://pubmed.ncbi.nlm.nih.gov/33824394/

The neurological symptoms of COVID-19: a systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services

Abstract:

Aims: In response to the rapid spread of COVID-19, this paper provides health professionals with better accessibility to available evidence, summarising findings from a systematic overview of systematic reviews of the neurological symptoms seen in patients with COVID-19. Implications of so-called ‘Long Covid’ on neurological services and primary care and similarities with other neurological disorders are discussed.

Methods: Firstly, a systematic overview of current reviews of neurological symptoms of COVID-19 was conducted. Secondly, the implications of these findings are discussed in relation to the potential effect on neurological services and the similarities in the experience of patients with COVID-19 and those with other neurological disorders. A total of 45 systematic reviews were identified within seven databases, published between 11 April 2020 and 15 October 2020, following a search in June 2020, updated on 20 October 2020.

Results: The results indicated that COVID-19 exhibits two types of neurological symptoms; life-threatening symptoms such as Guillain-Barre Syndrome (GBS) and encephalitis, and less devastating symptoms such as fatigue and myalgia. Many of these so-called lesser symptoms appear to be emerging as longer-term for some sufferers and have been recently labelled Long Covid. When compared, these less devastating symptoms are very similar to other neurological conditions such as chronic fatigue syndrome (CFS) and functional neurological disorder (FND).

Conclusion: Implications for neurological healthcare services in the United Kingdom (UK) may include longer waiting times and a need for more resources (including more qualified health professionals). There is also a possible change-effect on health professionals’ perceptions of other neurological conditions such as CFS and FND. Future research is recommended to explore changes in health professionals’ perceptions of neurological symptoms because of COVID-19.

Source: Wildwing T, Holt N. The neurological symptoms of COVID-19: a systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services. Ther Adv Chronic Dis. 2021 Jan 28;12:2040622320976979. doi: 10.1177/2040622320976979. PMID: 33796241; PMCID: PMC7970685. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970685/  (Full text)

We Already Know Enough to Avoid Making the Same Mistakes Again With Long COVID

Based on experience with past coronaviruses, the emerging challenge of prolonged symptoms after infection with the novel coronavirus 2019 (SARS-CoV-2) is unsurprising. Data from a large international web-based patient survey indicate substantial symptom overlap between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) at 6 months following the onset of first symptoms, including three quarters of participants suffering from fatigue and postexertional malaise, and over half with cognitive dysfunction.4 Apparent similarities between the presentations of long COVID and ME/CFS suggest that we may apply what we have learned from ME/CFS to long COVID.

Source: Todd E. Davenport, Staci R. Stevens, Jared Stevens, Christopher R. Snell, J. Mark Van Ness. We Already Know Enough to Avoid Making the Same Mistakes Again With Long COVID. Journal of Orthopedic & Sports Physical Therapy. Published online on March 10, 2021
https://doi.org/10.2519/jospt.blog.20210310