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Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies...
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Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—3rd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1383

Special Issue Editor

Prof. Dr. César Fernández-de-las-Peñas

E-Mail Website
Guest Editor
Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain
Interests: chronic pain; pain neuroscience education; manual therapy; central nervous system sensitization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The SARS-CoV-2 virus led to a worldwide outbreak of the disease. Current knowledge on SARS-CoV-2 acute infection has dramatically increased. However, healthcare systems and professionals are fighting against a “hidden” and underestimated consequence of the virus: the presence of long-lasting symptoms after acute infection. This condition has been called long COVID or post-COVID-19 syndrome. In fact, “long-haulers” is the term used to refer to subjects who have recovered from SARS-COV-2 infection but have developed post-COVID symptoms. Increasing studies have supported the presence of more than 100 potential symptoms after the acute phase of infection. Although long COVID as a term was proposed in July 2020, a potential consensus on the definition was only reached by the WHO in December 2021. However, several gaps are still present in the research regarding the identification, timeframe, mechanisms, and treatment strategies for the management of post-COVID symptoms. We are pleased to invite you to submit to this Special Issue, “Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications”.

This Special Issue aims to better understand the mechanisms underlying post-COVID-19 symptoms and post-COVID sequelae (associated with real tissue damage) to improve management of these patients. Identification of groups of long haulers according to mechanisms could lead to better treatment approaches. This Special Issue will focus on all these aspects of post-COVID symptoms and sequelae, a topic of emerging relevance due to the presence of millions of “long-haulers”. This is highly relevant since long COVID is independent of the SARS-CoV-2 variant or the implementation of vaccination programs. At the same time, research on adverse reactions or sequelae of COVID vaccines should also be of concern.  We invite researchers/clinicians to submit original articles and comprehensive reviews covering the identification or management of post-COVID subgroups to this Special Issue.

Prof. Dr. César Fernández-de-las-Peñas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • COVID-19
  • long COVID
  • pain
  • function
  • fatigue
  • dyspnoea
  • vaccine

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Published Papers (4 papers)

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Research

11 pages, 231 KiB  
Article
Autonomic Dysfunction and Low Cardio-Respiratory Fitness in Long-Term Post-COVID-19 Syndrome
by Radostina Cherneva, Zheyna Cherneva, Vania Youroukova, Tanya Kadiyska, Dinko Valev, Ebru Hayrula-Manaf and Vanyo Mitev
Biomedicines 2025, 13(5), 1138; https://doi.org/10.3390/biomedicines13051138 - 8 May 2025
Viewed by 110
Abstract
Purpose: Post-COVID-19 syndrome (PCS) is characterized by low cardio-respiratory fitness (CRF). Recent research focuses on the role of autonomic nervous system dysfunction (AD) as a potential contributor to the diminished exercise performance. The aim is to determine the prevalence of AD—chronotropic insufficiency (CI) [...] Read more.
Purpose: Post-COVID-19 syndrome (PCS) is characterized by low cardio-respiratory fitness (CRF). Recent research focuses on the role of autonomic nervous system dysfunction (AD) as a potential contributor to the diminished exercise performance. The aim is to determine the prevalence of AD—chronotropic insufficiency (CI) and abnormal heart rate recovery (HRR) in long-term PCS subjects and to analyse their association with exercise capacity. Patients and Methods: A total of 192 subjects with a history of SARS-CoV-2 infection were included. Chronic Fatigue Syndrome Questionnaire (CFSQ) was applied, and two symptomatic and asymptomatic emerged. Forty-seven had post-COVID complaints, persisting up to thirty months post-acute episode. CI and HRR were determined during the cardio-pulmonary exercise test (CPET). Results: Symptomatic subjects were divided into mild (20) and moderate-severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. Subjects with moderate-severe PCS showed lower peak VO2 (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to the mild/asymptomatic subjects. Diminished physical activity was established in 10 (37%) of the moderate-severe, 7 (35%) of the mildly symptomatic and 14 (29%) of the asymptomatic groups. The occurrence of AD in the mild/moderate-severe and control groups were, respectively, CI 35% vs. 81.5% vs. 12.5%. Abnormal HRR was, respectively, 20% vs. 33% vs. 8%. None of the subjects had depleted breathing reserve, dynamic hyperinflation, exercise bronchospasm or desaturation. Neither CI nor abnormal HRR correlated to peak O2. Conclusions: AD is present among long-term PCS subjects and may limit the cardio-respiratory response to exercise but is not independently associated with it. Assuming the multiorgan ANS innervation, it is highly probable that AD has diverse pathological pathways in the various PCS phenotypes and contributes differently by cerebral, cardiovascular, respiratory, peripheral or mixed pathways to the diminished neuro-cognitive and physical performance. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—3rd Edition)
11 pages, 240 KiB  
Article
Cardio-Respiratory Fitness and Fatigue in Post-COVID-19 Syndrome—A Three-Year Update
by Radostina Cherneva, Zheyna Cherneva, Vania Youroukova, Tanya Kadiyska, Dinko Valev, Ebru Myuyun Hayrula-Manaf and Vanyo Mitev
Biomedicines 2025, 13(5), 1097; https://doi.org/10.3390/biomedicines13051097 - 30 Apr 2025
Viewed by 286
Abstract
Background: Post-COVID-19 syndrome (PCS) is defined as the persistence of symptoms 3 months after acute SARS-CoV-2 infection. The long-term prevalence and clinical progression of PCS has not been established. Our aim was to investigate the symptoms in PCS patients, explore the degree of [...] Read more.
Background: Post-COVID-19 syndrome (PCS) is defined as the persistence of symptoms 3 months after acute SARS-CoV-2 infection. The long-term prevalence and clinical progression of PCS has not been established. Our aim was to investigate the symptoms in PCS patients, explore the degree of physical activity, according to the fatigue severity score, and analyze its association with basic cardio-pulmonary exercise testing (CPET) parameters. Methods: A total of 192 subjects with history of SARSCoV-2 infection were included. They filled in the Chronic Fatigue Syndrome Questionnaire (CFSQ) and were divided into symptomatic and asymptomatic groups. Forty-seven had persistent post-COVID complaints—reduced physical capacity, fatigue, dyspnea, sleep disturbances, muscle pain. CPET was performed and the pathophysiological parameters in the different fatigue severity groups were compared. Results: Subjects with persistent long-term PCS were divided into two groups—mild (20) and moderate–severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. The average period between the acute illness and the study was 1028 ± 214 days. Subjects with moderate–severe PCS had more symptoms during CPET (73.6% vs. 24.8% vs. 17.4%), as compared to mild/asymptomatic. The rate of perceived effort was subjective and did not correspond to the workload, heart, or breathing rate in the symptomatic group. These subjects were unable to reach the anaerobic threshold, compared to mild/asymptomatic subjects (51.8% vs. 25%, vs. 12.5%). Patients with moderate–severe PCS showed lower peak VO2 (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to mild/asymptomatic subjects. Conclusions: Long-term PCS is still present in up to 24% of the general population, more than thirty months after the acute episode. It is characterized by increased perception of symptom burden and diminished aerobic metabolism. A third of the long-term PCS exhibit lower cardio-respiratory fitness, independently from the severity of the symptoms. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—3rd Edition)
16 pages, 1697 KiB  
Article
A Machine Learning Model for Predicting Intensive Care Unit Admission in Inpatients with COVID-19 Using Clinical Data and Laboratory Biomarkers
by Alfonso Heriberto Hernández-Monsalves, Pablo Letelier, Camilo Morales, Eduardo Rojas, Mauricio Alejandro Saez, Nicolás Coña, Javiera Díaz, Andrés San Martín, Paola Garcés, Jesús Espinal-Enriquez and Neftalí Guzmán
Biomedicines 2025, 13(5), 1025; https://doi.org/10.3390/biomedicines13051025 - 24 Apr 2025
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Abstract
Background: Artificial intelligence tools can help improve the clinical management of patients with severe COVID-19. The aim of this study was to validate a machine learning model to predict admission to the Intensive Care Unit (ICU) in individuals with COVID-19. Methods: [...] Read more.
Background: Artificial intelligence tools can help improve the clinical management of patients with severe COVID-19. The aim of this study was to validate a machine learning model to predict admission to the Intensive Care Unit (ICU) in individuals with COVID-19. Methods: A total of 201 hospitalized patients with COVID-19 were included. Sociodemographic and clinical data as well as laboratory biomarker results were obtained from medical records and the clinical laboratory information system. Three machine learning models were generated, trained, and internally validated: logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost). The models were evaluated for sensitivity (Sn), specificity (Sp), area under the curve (AUC), precision (P), SHapley Additive exPlanation (SHAP) values, and the clinical utility of predictive models using decision curve analysis (DCA). Results: The predictive model included the following variables: type 2 diabetes mellitus (T2DM), obesity, absolute neutrophil and basophil counts, the neutrophil-to-lymphocyte ratio (NLR), and D-dimer levels on the day of hospital admission. LR showed an Sn of 0.67, Sp of 0.65, AUC of 0.74, and P of 0.66. RF achieved an Sn of 0.87, Sp of 0.83, AUC of 0.96, and P of 0.85. XGBoost demonstrated an Sn of 0.87, Sp of 0.85, AUC of 0.95, and P of 0.86. Conclusions: Among the evaluated models, XGBoost showed robust predictive performance (Sn = 0.87, Sp = 0.85, AUC = 0.95, P = 0.86) and a favorable net clinical benefit in the decision curve analysis, confirming its suitability for predicting ICU admission in COVID-19 and aiding clinical decision-making. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—3rd Edition)
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24 pages, 333 KiB  
Article
Long COVID and Associated Factors Among Chinese Residents Aged 16 Years and Older in Canada: A Cross-Sectional Online Study
by Matin Shariati, Kieran Luke Gill, Mark Peddle, Ying Cao, Fangli Xie, Xiao Han, Nan Lei, Rachel Prowse, Desai Shan, Lisa Fang, Vita Huang, Arianna Ding and Peizhong (Peter) Wang
Biomedicines 2025, 13(4), 953; https://doi.org/10.3390/biomedicines13040953 - 13 Apr 2025
Viewed by 368
Abstract
As the COVID-19 pandemic evolved, long COVID emerged as a significant threat to public health, characterized by one or more persistent symptoms impacting organ systems beyond 12 weeks of infection. Informative research has been derived from assessments of long COVID among the Chinese [...] Read more.
As the COVID-19 pandemic evolved, long COVID emerged as a significant threat to public health, characterized by one or more persistent symptoms impacting organ systems beyond 12 weeks of infection. Informative research has been derived from assessments of long COVID among the Chinese populace. However, none of these studies considered the COVID-19 experience of Chinese residents in Canada. Objectives: We aimed to fill this literature gap by delineating the long COVID experience, prevalence, and associated factors among a sample of Chinese residing in Canada during the pandemic. Methods: The present study employed a cross-sectional online survey questionnaire distributed to a sample of Canadian Chinese using a convenience sampling procedure from 22 December 2022 to 15 February 2023. Respondents were probed for sociodemographic background and health-, COVID-, and vaccine-related characteristics. Logistic LASSO regression was used for model building, and multivariate logistic regression was used to identify factors associated with developing long COVID. Results: Among 491 eligible participants, 63 (12.83%) reported experiencing long COVID with a mean duration of 5.31 (95% CI: 4.06–6.57) months and major symptoms including difficulty concentrating (21.67%), pain/discomfort (15.00%), as well as anxiety/depression (8.33%). Our final model identified significant associations between long COVID and two or more COVID-19 infections (OR = 23.725, 95% CI: 5.098–110.398, p < 0.0001), very severe/severe symptoms (OR = 3.177, 95% CI: 1.160–8.702, p = 0.0246), over-the-counter medicine (OR = 2.473, 95% CI: 1.035–5.909, p = 0.0416), and traditional Chinese medicine (OR = 8.259, 95% CI: 3.016–22.620, p < 0.0001). Further, we identified a significant protective effect of very good/good health status (OR = 0.247, 95% CI: 0.112–0.544, p = 0.0005). Conclusions: Long COVID effected a notable proportion of Canadian Chinese for a prolonged period during the COVID-19 pandemic. Our findings underscore the importance of preexisting health status and reinfection prevention when managing long COVID. Moreover, our work indicates an association between using over-the-counter medicine or traditional Chinese medicine and long COVID experience among Canadian Chinese. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—3rd Edition)
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