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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—2nd 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 2024 | Viewed by 6126

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

Related Special Issue

Published Papers (6 papers)

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Research

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24 pages, 6972 KiB  
Article
Respiratory SARS-CoV-2 Infection Causes Skeletal Muscle Atrophy and Long-Lasting Energy Metabolism Suppression
by Sachiko T. Homma, Xingyu Wang, Justin J. Frere, Adam C. Gower, Jingsong Zhou, Jean K. Lim, Benjamin R. tenOever and Lan Zhou
Biomedicines 2024, 12(7), 1443; https://doi.org/10.3390/biomedicines12071443 - 28 Jun 2024
Viewed by 471
Abstract
Muscle fatigue represents the most prevalent symptom of long-term COVID, with elusive pathogenic mechanisms. We performed a longitudinal study to characterize histopathological and transcriptional changes in skeletal muscle in a hamster model of respiratory SARS-CoV-2 infection and compared them with influenza A virus [...] Read more.
Muscle fatigue represents the most prevalent symptom of long-term COVID, with elusive pathogenic mechanisms. We performed a longitudinal study to characterize histopathological and transcriptional changes in skeletal muscle in a hamster model of respiratory SARS-CoV-2 infection and compared them with influenza A virus (IAV) and mock infections. Histopathological and bulk RNA sequencing analyses of leg muscles derived from infected animals at days 3, 30, and 60 post-infection showed no direct viral invasion but myofiber atrophy in the SARS-CoV-2 group, which was accompanied by persistent downregulation of the genes related to myofibers, ribosomal proteins, fatty acid β-oxidation, tricarboxylic acid cycle, and mitochondrial oxidative phosphorylation complexes. While both SARS-CoV-2 and IAV infections induced acute and transient type I and II interferon responses in muscle, only the SARS-CoV-2 infection upregulated TNF-α/NF-κB but not IL-6 signaling in muscle. Treatment of C2C12 myotubes, a skeletal muscle cell line, with combined IFN-γ and TNF-α but not with IFN-γ or TNF-α alone markedly impaired mitochondrial function. We conclude that a respiratory SARS-CoV-2 infection can cause myofiber atrophy and persistent energy metabolism suppression without direct viral invasion. The effects may be induced by the combined systemic interferon and TNF-α responses at the acute phase and may contribute to post-COVID-19 persistent muscle fatigue. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
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10 pages, 464 KiB  
Article
COVID-19 Infection in Autosomal Dominant Polycystic Kidney Disease and Chronic Kidney Disease Patients: Progression of Kidney Disease
by Silvia Lai, Francesca Tinti, Adolfo Marco Perrotta, Luca Salomone, Rosario Cianci, Paolo Izzo, Sara Izzo, Luciano Izzo, Claudia De Intinis, Chiara Pellicano and Antonietta Gigante
Biomedicines 2024, 12(6), 1301; https://doi.org/10.3390/biomedicines12061301 - 12 Jun 2024
Viewed by 1193
Abstract
Introduction: the COVID-19 pandemic has brought to light the intricate interplay between viral infections and preexisting health conditions. In the field of kidney diseases, patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Chronic Kidney Disease (CKD) face unique challenges when exposed to [...] Read more.
Introduction: the COVID-19 pandemic has brought to light the intricate interplay between viral infections and preexisting health conditions. In the field of kidney diseases, patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Chronic Kidney Disease (CKD) face unique challenges when exposed to the SARS-CoV-2 virus. This study aims to evaluate whether SARS-CoV-2 virus infection impacts renal function differently in patients suffering from ADPKD and CKD when compared to patients suffering only from CKD. Materials and methods: clinical data from 103 patients were collected and retrospectively analyzed. We compared the renal function of ADPKD and CKD patients at two distinct time points: before COVID-19 infection (T0) and 1 year after the infection (T1). We studied also a subpopulation of 37 patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min and affected by ADPKD and CKD. Results: clinical data were obtained from 59 (57.3%) ADPKD patients and 44 (42.7%) CKD patients. At T1, ADPKD patients had significantly higher serum creatinine levels compared to CKD patients, and a significantly lower eGFR was observed only in ADPKD patients with eGFR < 60 mL/min compared to CKD patients (p < 0.01, p < 0.05; respectively). Following COVID-19 infection, ADPKD–CKD patients exhibited significantly higher variation in both median serum creatinine (p < 0.001) and median eGFR (p < 0.001) compared to CKD patients. Conclusion: the interplay between COVID-19 and kidney disease is complex. In CKD patients, the relationship between COVID-19 and kidney disease progression is more established, while limited studies exist on the specific impact of COVID-19 on ADPKD patients. Current evidence does not suggest that ADPKD patients are at a higher risk of SARS-CoV-2 infection; however, in our study we showed a significant worsening of the renal function among ADPKD patients, particularly those with an eGFR < 60 mL/min, in comparison to patients with only CKD after a one-year follow-up from COVID-19 infection. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
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14 pages, 1068 KiB  
Article
Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) for Patients—3-Year Follow-Up of Patients with Chronic Kidney Disease
by Rumen Filev, Mila Lyubomirova, Boris Bogov, Krassimir Kalinov, Julieta Hristova, Dobrin Svinarov, Alexander Garev and Lionel Rostaing
Biomedicines 2024, 12(6), 1259; https://doi.org/10.3390/biomedicines12061259 - 5 Jun 2024
Viewed by 606
Abstract
Post-acute sequelae of SARS-CoV-2 (PASC) is a significant health concern, particularly for patients with chronic kidney disease (CKD). This study investigates the long-term outcomes of individuals with CKD who were infected with COVID-19, focusing on their health status over a three-year period post-infection. [...] Read more.
Post-acute sequelae of SARS-CoV-2 (PASC) is a significant health concern, particularly for patients with chronic kidney disease (CKD). This study investigates the long-term outcomes of individuals with CKD who were infected with COVID-19, focusing on their health status over a three-year period post-infection. Data were collected from both CKD and non-CKD patients who survived SARS-CoV-2 infection and were followed for three years as part of a research study on the impact, prognosis, and consequences of COVID-19 infection in CKD patients. In this prospective cohort study, we analyzed clinical records, laboratory findings, and patient-reported outcomes assessed at intervals during follow-up. The results indicated no permanent changes in renal function in any of the groups analyzed, although patients without CKD exhibited faster recovery over time. Furthermore, we examined the effect of RAAS-blocker therapy over time, finding no influence on PASC symptoms or renal function recovery. Regarding PASC symptoms, most patients recovered within a short period, but some required prolonged follow-up and specialized post-recovery management. Following up with patients in the post-COVID-19 period is crucial, as there is still insufficient information and evidence regarding the long-term effects, particularly in relation to CKD. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
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15 pages, 3802 KiB  
Article
Hemoglobin and Its Relationship with Fatigue in Long-COVID Patients Three to Six Months after SARS-CoV-2 Infection
by Somayeh Bazdar, Lizan D. Bloemsma, Nadia Baalbaki, Jelle M. Blankestijn, Merel E. B. Cornelissen, Rosanne J. H. C. G. Beijers, Brigitte M. Sondermeijer, Yolanda van Wijck, George S. Downward and Anke H. Maitland-van der Zee
Biomedicines 2024, 12(6), 1234; https://doi.org/10.3390/biomedicines12061234 - 1 Jun 2024
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Abstract
Background: While some long-term effects of COVID-19 are respiratory in nature, a non-respiratory effect gaining attention has been a decline in hemoglobin, potentially mediated by inflammatory processes. In this study, we examined the correlations between hemoglobin levels and inflammatory biomarkers and evaluated the [...] Read more.
Background: While some long-term effects of COVID-19 are respiratory in nature, a non-respiratory effect gaining attention has been a decline in hemoglobin, potentially mediated by inflammatory processes. In this study, we examined the correlations between hemoglobin levels and inflammatory biomarkers and evaluated the association between hemoglobin and fatigue in a cohort of Long-COVID patients. Methods: This prospective cohort study in the Netherlands evaluated 95 (mostly hospitalized) patients, aged 40–65 years, 3–6 months post SARS-CoV-2 infection, examining their venous hemoglobin concentration, anemia (hemoglobin < 7.5 mmol/L in women and <8.5 mmol/L in men), inflammatory blood biomarkers, average FSS (Fatigue Severity Score), demographics, and clinical features. Follow-up hemoglobin was compared against hemoglobin during acute infection. Spearman correlation was used for assessing the relationship between hemoglobin concentrations and inflammatory biomarkers, and the association between hemoglobin and fatigue was examined using logistic regression. Results: In total, 11 (16.4%) participants were suffering from anemia 3–6 months after SARS-CoV-2 infection. The mean hemoglobin value increased by 0.3 mmol/L 3–6 months after infection compared to the hemoglobin during the acute phase (p-value = 0.003). Whilst logistic regression showed that a 1 mmol/L greater increase in hemoglobin is related to a decrease in experiencing fatigue in Long-COVID patients (adjusted OR 0.38 [95%CI 0.13–1.09]), we observed no correlations between hemoglobin and any of the inflammatory biomarkers examined. Conclusion: Our results indicate that hemoglobin impairment might play a role in developing Long-COVID fatigue. Further investigation is necessary to identify the precise mechanism causing hemoglobin alteration in these patients. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
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14 pages, 670 KiB  
Article
Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome
by Madalina Boruga, Susa Septimiu-Radu, Prashant Sunil Nandarge, Ahmed Elagez, Gabriela Doros, Voichita Elena Lazureanu, Emil Robert Stoicescu, Elena Tanase, Roxana Iacob, Andreea Dumitrescu, Adrian Vasile Bota, Coralia Cotoraci and Melania Lavinia Bratu
Biomedicines 2024, 12(5), 950; https://doi.org/10.3390/biomedicines12050950 - 24 Apr 2024
Viewed by 897
Abstract
The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in [...] Read more.
The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the “Victor Babes” Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study’s findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
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Review

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20 pages, 1385 KiB  
Review
Platelet-Rich Plasma (PRP) in the Treatment of Long COVID Olfactory Disorders: A Comprehensive Review
by Antonino Maniaci, Salvatore Lavalle, Edoardo Masiello, Jerome R. Lechien, Luigi Vaira, Paolo Boscolo-Rizzo, Mutali Musa, Caterina Gagliano and Marco Zeppieri
Biomedicines 2024, 12(4), 808; https://doi.org/10.3390/biomedicines12040808 - 5 Apr 2024
Viewed by 1325
Abstract
Background: Long COVID has brought numerous challenges to healthcare, with olfactory dysfunction (OD) being a particularly distressing outcome for many patients. The persistent loss of smell significantly diminishes the affected individual’s quality of life. Recent attention has been drawn to the potential of [...] Read more.
Background: Long COVID has brought numerous challenges to healthcare, with olfactory dysfunction (OD) being a particularly distressing outcome for many patients. The persistent loss of smell significantly diminishes the affected individual’s quality of life. Recent attention has been drawn to the potential of platelet-rich plasma (PRP) therapy as a treatment for OD. This comprehensive review aims to evaluate the effectiveness of PRP therapy in ameliorating OD, especially when associated with long-term COVID-19. Methods: We executed a comprehensive search of the literature, encompassing clinical trials and observational studies that utilized PRP in treating OD limited to COVID-19. We retrieved and comprehensively discussed data such as design, participant demographics, and reported outcomes, focusing on the efficacy and safety of PRP therapy for OD in COVID-19 patients. Results: Our comprehensive analysis interestingly found promising perspectives for PRP in OD following COVID-19 infection. The collective data indicate that PRP therapy contributed to a significant improvement in olfactory function after COVID-19 infection. Conclusions: The evidence amassed suggests that PRP is a promising and safe therapeutic option for OD, including cases attributable to Long COVID-19. The observed uniform enhancement of olfactory function in patients receiving PRP highlights the necessity for well-designed, controlled trials. Such studies would help to refine treatment protocols and more definitively ascertain the efficacy of PRP in a broader, more varied patient cohort. Full article
(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: New Onset of Acute and Chronic Liver Parenchymal Diseases Post-COVID-19 Infection: A Systematic Review
Author: Zakaria
Highlights: Liver injury has been reported as one of the post-COVID-19 complications. The proposed mechanisms of liver damage are either direct viral attack or indirect factors such as inflammation. Further studies should focus on how factors surrounding COVID-19 affects liver complications following infection and to incorporate longer follow-up periods, after recovering from COVID-19.

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