Exploring the Post-COVID-19 Syndrome: Findings, Mechanisms, Research Challenges, and Strategies

A special issue of Diseases (ISSN 2079-9721).

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 12753

Special Issue Editor


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Guest Editor
Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Via E. Ramarini, Monterotondo Scalo, 00015 Rome, Italy
Interests: NeuroCOVID-19; SARS-CoV-2; post-COVID-19 syndrome; microRNA; RNA-induced silencing complex (RISC); RNA-binding protein; neurodegenerative disease; Alzheimer’s disease; small non-coding RNA; RNA metabolism; cellular and molecular neurobiology; translational biomedicine
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Special Issue Information

Dear Colleagues,

In 2022, the World Health Organization used a Delphi consensus method that involved patients and clinicians to define LONG COVID: symptoms that linger beyond 3 months of a probable or confirmed SARS-CoV-2 infection, which last at least 2 months and cannot be explained by an alternative diagnosis. Post-COVID-19 syndrome (PACS) affects 20‒30% of unvaccinated individuals for from three to six months after SARS-CoV-2 infection, and definitive diagnostic criteria can be determined. We need an effective strategy to contain and reduce the impact of the post-COVID-19 condition.

Persistent fatigue, excessive tiredness, muscle weakness, widespread pain, and perceived deterioration in health, dyspnea, persistent cough and decreased ability to expand the rib cage, tightness and pain in the chest, tachycardia and palpitations with minimal effort, arrhythmias, and changes in blood pressure characterize PACS. In addition, PACS patients are affected by neurological impairment, neuropsychiatric and psycho-sensory symptoms, loss of olfactory and taste function with anosmia and dysgeusia, and neurocognitive symptoms defined as ‘brain fog’ and sleep disturbance named NEUROCOVID, which reduces physical and mental life quality.

This Special Issue in Diseases focuses on the current state of knowledge on Long COVID/post-COVID-19 syndrome and different aspects of integrated models of translational biomedicine. Experimental works, reviews, clinical cases, and hypotheses addressing the development of knowledge regarding post-COVID-19 syndrome and clinical and therapeutic perspectives are of particular interest for this Special Issue. Furthermore, articles presenting data on molecular and cellular mechanisms investigations are particularly welcome.

Qualitative as well as quantitative research papers, reviews, case reports, hypotheses, and guidelines addressing the development of knowledge regarding post-COVID-19 syndrome will be considered for this Special Issue, but other types of contributions will also be taken into consideration for publication. We look forward to your participation in this Special Issue to increase and share knowledge on post-COVID-19 scientific research.

Dr. Christian Barbato
Guest Editor

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Keywords

  • SARS-CoV-2
  • post-COVID-19 syndrome
  • neuroCOVID
  • neurosensorial
  • cognitive
  • biomarkers
  • translational biomedicine
  • olfactory diseases
  • PACS
  • Long COVID
  • persistent fatigue
  • dyspnea
  • sleep disturbance

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Published Papers (5 papers)

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12 pages, 1778 KiB  
Article
Patterned Sensory Enhancement, a Music Rehabilitation Therapy for Elderly Patients with Neuromotor Deficit during the COVID-19 Pandemic: A Pilot Study
by Iulia Toma, Anca Dinu, Ahmed Abu-Awwad, Mihai-Alexandru Sandesc, Simona-Alina Abu-Awwad, Razvan Nitu and Mihai Popean
Diseases 2024, 12(1), 11; https://doi.org/10.3390/diseases12010011 - 31 Dec 2023
Cited by 2 | Viewed by 2160
Abstract
(1) Background: The Patterned Sensory Enhancement (PSE) technique refers to a music-based rehabilitation therapy strategy used in neurological pathologies. (2) Methods: This study aims at developing a music-drill protocol for recovery in elderly patients with neuromuscular degenerative pathologies. Each music drill is based [...] Read more.
(1) Background: The Patterned Sensory Enhancement (PSE) technique refers to a music-based rehabilitation therapy strategy used in neurological pathologies. (2) Methods: This study aims at developing a music-drill protocol for recovery in elderly patients with neuromuscular degenerative pathologies. Each music drill is based on a number of specific music-composition parameters. The conclusions represent suggestions for further enhancing the PSE technique through collaborations between the rehabilitation team and the musicians involved due to the importance of the music stimuli used as a therapy. (3) Results: The music-composition parameters used in this study relate to the existence of music homogeneity factors such as the key signature and rhythm; the importance of the major scale and the tonal system in general; the obvious music suggestions of movement, repetition or absence of movement; the importance of rhythm; the introduction of musical instruments in order to harmonize the music material as much as possible; the connection between PSE music along with patients’ musical taste and the musical recording as a therapy during patient outcare; (4) Conclusions: The therapy efficiency was observed by measurements taken before and after the therapeutic intervention by means of a Takei dynamometer. The present study asserts that for a patient undergoing the PSE technique, the researcher should compose personalized music material adapted to each patient’s peculiarities. Full article
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12 pages, 577 KiB  
Article
Post-Infection Oscillometry and Pulmonary Metrics in SARS-CoV-2 Patients: A 40-Day Follow-Up Study
by Noemi Suppini, Cristian Oancea, Ovidiu Fira-Mladinescu, Daniel Traila, Camelia Pescaru, Monica Steluta Marc, Diana Manolescu, Emanuela Vastag, Ayesha Ali, Elena Hogea and Ciprian Nicolae Pilut
Diseases 2023, 11(3), 102; https://doi.org/10.3390/diseases11030102 - 5 Aug 2023
Cited by 3 | Viewed by 1641
Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had significant impacts on pulmonary function. This study aimed to comprehensively evaluate pulmonary function and structure in patients 40 days post-SARS-CoV-2 infection, employing an array of testing methodologies including spirometry, plethysmography, forced oscillometry, and [...] Read more.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had significant impacts on pulmonary function. This study aimed to comprehensively evaluate pulmonary function and structure in patients 40 days post-SARS-CoV-2 infection, employing an array of testing methodologies including spirometry, plethysmography, forced oscillometry, and CT scanning. It also sought to establish potential correlations between these metrics and evaluate if forced oscillometry could provide additional value in post-infective lung function assessment. A 40-day post-infection follow-up observational study was conducted involving 66 patients with confirmed SARS-CoV-2 infection. The results revealed decreases in FVC and FEF25–75 with the increasing severity of COVID-19. Specifically, patients with severe symptoms exhibited statistically significant decreases in FVC (mean = 86.8) compared with those with mild symptoms (mean = 106.0; p = 0.018). The FEF25–75 showed a similar trend, with severe patients exhibiting a mean of 77.7 compared with 82.9 in the mild group (p = 0.017). Furthermore, resonant frequency (RF) increased with disease severity, with the severe group exhibiting a statistically significant increase (mean = 17.4) compared with the mild group (mean = 14.3; p = 0.042). CT scans showed an increase in ground-glass opacities with disease severity, with 81.8% of severe patients demonstrating this finding (p = 0.037). Multiple regression analysis revealed that Reactance at 4 Hz (X4), Forced Expiratory Flow 25–75% (FEF25–75), and Resonant Frequency (RF) were significantly related to COVID-19 severity. Specifically, for each unit increase in these factors, the risk of the event was estimated to increase by a factor of 3.16, 2.09, and 1.90, respectively. Conversely, Resistance at 4 Hz (R4) and Airway Resistance (RAW) were found to significantly decrease the event hazard, highlighting their potential protective role. Spirometry, plethysmography, and forced oscillometry are effective in assessing these changes. Forced oscillometry may be particularly beneficial in identifying subtle changes in lung function post-COVID-19. Further studies are warranted to validate these findings and develop strategies to manage post-infective pulmonary changes in SARS-CoV-2 patients. Full article
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10 pages, 1355 KiB  
Case Report
Neuropathic Corneal Pain after Coronavirus Disease 2019 (COVID-19) Infection
by Natalie Shi Qi Wong, Chang Liu, Molly Tzu-Yu Lin, Isabelle Xin Yu Lee, Louis Tong and Yu-Chi Liu
Diseases 2024, 12(2), 37; https://doi.org/10.3390/diseases12020037 - 9 Feb 2024
Cited by 1 | Viewed by 2238
Abstract
Introduction: This is a case report of a patient with neuropathic corneal pain after coronavirus disease 2019 (COVID-19) infection. Methods: A previously healthy 27-year-old female presented with bilateral eye pain accompanied by increased light sensitivity 5 months after COVID-19 infection. She was diagnosed [...] Read more.
Introduction: This is a case report of a patient with neuropathic corneal pain after coronavirus disease 2019 (COVID-19) infection. Methods: A previously healthy 27-year-old female presented with bilateral eye pain accompanied by increased light sensitivity 5 months after COVID-19 infection. She was diagnosed with neuropathic corneal pain based on clear corneas without fluorescein staining, alongside the presence of microneuromas, dendritic cells, and activated stromal keratocytes identified bilaterally on in vivo confocal microscopy. Results: The patient’s tear nerve growth factor, substance P, and calcitonin gene-related peptide levels were 5.9 pg/mL, 2978.7 pg/mL, and 1.1 ng/mL, respectively, for the right eye and 23.1 pg/mL, 4798.7 pg/mL, and 1.2 ng/mL, respectively, for the left eye, suggesting corneal neuroinflammatory status. After 6 weeks of topical 0.1% flurometholone treatment, decreased microneuroma size, less extensive dendritic cells, and reduced tear nerve growth factor and substance P levels were observed. The scores on the Ocular Pain Assessment Survey showed an improvement in burning sensation and light sensitivity, decreasing from 80% and 70% to 50% for both. Conclusions: Neuropathic corneal pain is a potential post-COVID-19 complication that warrants ophthalmologists’ and neurologists’ attention. Full article
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12 pages, 558 KiB  
Systematic Review
Long COVID and Physical Therapy: A Systematic Review
by Juan Carlos Sánchez-García, Andrés Reinoso-Cobo, Beatriz Piqueras-Sola, Jonathan Cortés-Martín, María José Menor-Rodríguez, Raquel Alabau-Dasi and Raquel Rodríguez-Blanque
Diseases 2023, 11(4), 163; https://doi.org/10.3390/diseases11040163 - 9 Nov 2023
Cited by 12 | Viewed by 3949
Abstract
Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, “brain fog”, respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a [...] Read more.
Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, “brain fog”, respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a crucial aspect of the management of patients with long COVID, as it can help improve symptoms and overall physical function. The investigation of long COVID poses significant challenges due to the diversity and variability of symptoms, lack of clear diagnostic criteria, and limited understanding of the underlying mechanisms. The aim of this study is to conduct a systematic review of studies conducted in patients with long COVID in conjunction with interventions targeting respiratory function, particularly involving physical activity. To this end, we conducted a systematic review to analyze studies conducted on treatment programs for long COVID based on some form of physical activity. The protocol of the review was registered in the PROSPERO website, and the databases PubMed, Scopus, CINAHL and WOS were searched. Of the 62 initial articles, six were included in the review. The results obtained have positive implications for the advancement of physical activity as a therapeutic intervention for individuals with long COVID-19 and the conceptualization of evidence-based treatment protocols. Statistically significant results have been observed in studies of at least 6 weeks duration, in which inspiratory muscle training exercises are proposed. Further research is needed to better understand long COVID and develop effective treatment strategies. Full article
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9 pages, 2250 KiB  
Case Report
Neurofilament Expression as a Biomarker of Post-COVID-19 Sudden Sensorineural Hearing Loss
by Federica Zoccali, Carla Petrella, Maria Antonella Zingaropoli, Marco Fiore, Massimo Ralli, Antonio Minni and Christian Barbato
Diseases 2023, 11(3), 92; https://doi.org/10.3390/diseases11030092 - 29 Jun 2023
Cited by 1 | Viewed by 2013
Abstract
Sudden sensorineural hearing loss (SSHL) affects a patient’s quality of life and requires rapid treatment. The etiology is viral, vascular, and autoimmune, even though, in most cases, it remains idiopathic SSHL. Since 2019, several different complications have been identified following COVID-19 infection. The [...] Read more.
Sudden sensorineural hearing loss (SSHL) affects a patient’s quality of life and requires rapid treatment. The etiology is viral, vascular, and autoimmune, even though, in most cases, it remains idiopathic SSHL. Since 2019, several different complications have been identified following COVID-19 infection. The post-COVID-19 ENT manifestations reported in the literature are sore throat, headache, pharyngeal erythema, nasal obstruction, rhinorrhea, upper respiratory tract infection, and tonsil enlargement. Cases of SSHL, vestibular neuronitis, and audio-vestibular disorders (such as tinnitus, dizziness, and vertigo) have also been reported, albeit in a smaller percentage of patients. We reported our experience of a case of post-COVID-19 SSHL in the absence of any other type of post-COVID symptoms or brain and internal auditory canal magnetic resonance imaging and magnetic resonance angiography modifications. We aimed to identify a serological biomarker of sudden sensorineural hearing loss, and we also dosed and monitored the value of the serum neurofilament light (NfL). the best of our knowledge, this is the first report that associates SSHL and the serological increase in NfL as a potential biomarker of neuronal-disease-related damage. Full article
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