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Viruses
Special Issues
Beyond Acute: Navigating Long COVID and Post-Viral Complications
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Beyond Acute: Navigating Long COVID and Post-Viral Complications

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 15 April 2026 | Viewed by 11066

Special Issue Editors

Dr. Maggie Bartlett

E-Mail Website
Guest Editor
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Interests: immunity; neurological viral infections
Prof. Dr. Janko Nikolich-Žugich

E-Mail Website
Guest Editor
Department of Immunobiology and the University of Arizona Center on Aging, University of Arizona College of Medicine – Tucson, Tucson, AZ 85724, USA
Interests: COVID-19; Postacute Sequelae of SARS-CoV-2 Infection; basic mechanisms of T-cell function; immunity to infection in older adults; vaccines and biomarkers of declining immunity in the elderly; immune rejuvenation; immune monitoring in chronic conditions of aging and the impact of inflammation and nutritional intervention in aging, immunity and metabolic disorders
Dr. Rubeshan Perumal

E-Mail Website
Guest Editor
Centre for the AIDS Programme of Research in South Africa, Durban 4001, South Africa
Interests: Post COVID-19 lung disease; lung infection and immunity
Prof. Dr. Anders Vahlne

E-Mail Website
Guest Editor
Professor Emeritus in Clinical Virology, Karolinska Institute, 171 77 Solna, Sweden
Interests: long COVID; herpes simplex virus neurobiology and pathogenesis; HIV pathogenesis; virus diagnostics

Special Issue Information

Dear Colleagues,

The special issue on acute viral infection complications delves into post-acute sequelae (PASC) or long COVID, exploring its mechanisms, clinical manifestations, and management. It covers immune-mediated complications, such as autoimmune disorders, triggered by viral mimicry or dysregulated immune responses. The issue also addresses neurological, respiratory, cardiovascular, and pregnancy-related complications arising from viral infections. Through research articles and case studies, it aims to enhance understanding of these complications, informing clinical practice, public health strategies, and ongoing research for better patient outcomes globally.

Dr. Maggie Bartlett
Prof. Dr. Janko Nikolich-Žugich
Dr. Rubeshan Perumal
Prof. Dr. Anders Vahlne
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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. Viruses 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

  • long COVID
  • post-viral complications
  • dysregulated immune responses
  • neurological complications
  • respiratory complications
  • cardiovascular complications
  • pregnancy-related complications

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Published Papers (4 papers)

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Research

18 pages, 5005 KB  
Article
Long-Term Transcriptomic Reprogramming in Peripheral Blood Mononuclear Cells of Severe COVID-19 Survivors Reveals Pro-Oncogenic Signatures and Cancer-Associated Hub Genes
by Pelin Duru Cetinkaya, Ozgecan Kayalar, Vahap Eldem, Serap Argun Baris, Nurdan Kokturk, Selim Can Kuralay, Hadi Rajabi, Nur Konyalilar, Deniz Mortazavi, Seval Kubra Korkunc, Sinem Erkan, Gizem Tuse Aksoy, Gul Eyikudamaci, Pelin Pinar Deniz, Oya Baydar Toprak, Pinar Yildiz Gulhan, Gulseren Sagcan, Neslihan Kose Kabil, Aysegul Tomruk Erdem, Fusun Fakili, Onder Ozturk, Ilknur Basyigit, Hasim Boyaci, Emel Azak, Tansu Ulukavak Ciftci, Ipek Kivilcim Oguzulgen, Hasan Selcuk Ozger, Pinar Aysert Yildiz, Ismail Hanta, Ozlem Ataoglu, Merve Ercelik, Caglar Cuhadaroglu, Hacer Kuzu Okur, Muge Meltem Tor, Esra Nurlu Temel, Seval Kul, Yıldız Tutuncu, Oya Itil and Hasan Bayramadd Show full author list remove Hide full author list
Viruses 2025, 17(12), 1608; https://doi.org/10.3390/v17121608 - 12 Dec 2025
Viewed by 1554
Abstract
This study examined the long-term transcriptomic reprogramming in peripheral blood mononuclear cells (PBMCs) of severe COVID-19 patients and its effects for cancer development. RNA sequencing was conducted on PBMCs obtained from healthy controls, COVID-19 patients without pneumonia, and COVID-19 patients exhibiting severe pneumonia [...] Read more.
This study examined the long-term transcriptomic reprogramming in peripheral blood mononuclear cells (PBMCs) of severe COVID-19 patients and its effects for cancer development. RNA sequencing was conducted on PBMCs obtained from healthy controls, COVID-19 patients without pneumonia, and COVID-19 patients exhibiting severe pneumonia one year post-infection. Differential gene expression analysis identified a sustained pro-oncogenic molecular signature, especially among severe COVID-19 patients. Functional enrichment analysis revealed a substantial enrichment of cancer-associated pathways, encompassing apoptosis, viral carcinogenesis, and transcriptional dysregulation. Notably, the autophagy-related gene SQSTM1/P62 was recognized as a distinctive hub gene within the severe COVID-19 patients, interacting with pivotal genes associated with inflammation, apoptosis, and cancer advancement. Survival analysis demonstrated that elevated expression of COVID-19-associated hub genes correlated with unfavorable prognosis in various cancer types, including adrenocortical carcinoma, bladder urothelial carcinoma, and brain lower-grade glioma. These findings indicate that severe COVID-19 infection may establish a systemic milieu favorable to cancer development or recurrence, highlighting the necessity of prolonged oncological monitoring in these patients. Finding specific molecular targets and pathways can help us understand how COVID-19 might be linked to a higher risk of cancer. Full article
(This article belongs to the Special Issue Beyond Acute: Navigating Long COVID and Post-Viral Complications)
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15 pages, 783 KB  
Article
The Relationship Between Hemodynamic Responses During Head-Up Tilt Testing and Parameters of Infection in Post-COVID Syndrome, Chronic Fatigue Syndrome, and Late-Stage Lyme Disease
by Branislav Milovanovic, Nikola Markovic, Masa Petrovic, Smiljana Stojanovic, Vasko Zugic, Milijana Ostojic and Milovan Bojic
Viruses 2025, 17(11), 1430; https://doi.org/10.3390/v17111430 - 28 Oct 2025
Viewed by 1258
Abstract
Autonomic nervous system (ANS) dysfunction has emerged as a central feature of post-infectious syndromes, including post-COVID syndrome (PCS), chronic fatigue syndrome (CFS), and late-stage Lyme disease. This cross-sectional study included 1036 patients evaluated in the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases [...] Read more.
Autonomic nervous system (ANS) dysfunction has emerged as a central feature of post-infectious syndromes, including post-COVID syndrome (PCS), chronic fatigue syndrome (CFS), and late-stage Lyme disease. This cross-sectional study included 1036 patients evaluated in the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje,” divided into four groups: PCS, CFS after COVID-19, CFS of insidious onset, and Lyme disease. All patients underwent head-up tilt testing (HUTT), and serological testing was performed in accredited institutions. The Lyme disease group demonstrated the highest prevalence of positive HUTT responses and a significantly greater frequency of orthostatic hypotension and syncope. Approximately 50–65% of patients in the PCS and Lyme groups were positive for IgM antibodies against at least one microorganism, with more than 10% showing positivity for three or more pathogens. Logistic regression analysis revealed that, beyond classical hemodynamic parameters, antibody status served as a significant predictor of HUTT outcomes, with specific associations identified for HSV-1, HHV-6, Coxiella burnetii, Toxoplasma gondii, and Borrelia spp. Multinomial regression further indicated that negative IgG antibodies, particularly to HSV-1 and VZV, predicted Lyme disease group membership. These findings support the hypothesis that ANS dysfunction in post-infectious syndromes may be driven by persistent or prior infections, highlighting the need for integrative diagnostic approaches. Full article
(This article belongs to the Special Issue Beyond Acute: Navigating Long COVID and Post-Viral Complications)
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14 pages, 1459 KB  
Article
A New Approach to the Etiology of Syncope: Infection as a Cause
by Branislav Milovanovic, Nikola Markovic, Masa Petrovic, Vasko Zugic, Milijana Ostojic, Milica Dragicevic-Antonic and Milovan Bojic
Viruses 2025, 17(3), 427; https://doi.org/10.3390/v17030427 - 15 Mar 2025
Cited by 1 | Viewed by 3087
Abstract
Background/Objectives: Syncope is a common clinical occurrence, with neurally mediated and orthostatic types accounting for about 75% of cases. The exact pathophysiological mechanisms remain unclear, with recent evidence suggesting autonomic nervous system damage and a potential infectious etiology. This study aimed to examine [...] Read more.
Background/Objectives: Syncope is a common clinical occurrence, with neurally mediated and orthostatic types accounting for about 75% of cases. The exact pathophysiological mechanisms remain unclear, with recent evidence suggesting autonomic nervous system damage and a potential infectious etiology. This study aimed to examine the role of infection in the development of syncope and orthostatic hypotension (OH). Methods: The cross-sectional study included 806 patients from the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje”. Patients were divided into three groups: unexplained recurrent syncope (n = 506), syncope with OH during the head-up tilt test (HUTT) (n = 235), and OH without a history of syncope (n = 62). All participants underwent the HUTT, and 495 underwent serological testing for various microorganisms. Data were analyzed using chi-squared tests and binary and multinomial logistic regression. Results: The HUTT was positive in 90.6% of patients with syncope and OH, compared with 61.6% with syncope alone (p < 0.001). Serological testing revealed that 57.85% of syncope patients, 62.9% of syncope with OH patients, and 78% of OH patients had positive IgM antibodies to at least one microorganism. Multivariate analysis indicated that IgM antibodies to Coxsackievirus and Epstein–Barr virus were significant predictors of OH. Conclusions: This study demonstrated a potential association between infections and syncope/OH. Further investigation into the role of infectious agents in autonomic dysfunction is warranted to clarify the underlying mechanisms of syncope and OH. Full article
(This article belongs to the Special Issue Beyond Acute: Navigating Long COVID and Post-Viral Complications)
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11 pages, 730 KB  
Article
Persistence of Long COVID Symptoms Two Years After SARS-CoV-2 Infection: A Prospective Longitudinal Cohort Study
by Gili Joseph, Ili Margalit, Yael Weiss-Ottolenghi, Carmit Rubin, Havi Murad, Raquel C. Gardner, Noam Barda, Elena Ben-Shachar, Victoria Indenbaum, Mayan Gilboa, Sharon Alroy-Preis, Yitshak Kreiss, Yaniv Lustig and Gili Regev-Yochay
Viruses 2024, 16(12), 1955; https://doi.org/10.3390/v16121955 - 20 Dec 2024
Cited by 11 | Viewed by 3901
Abstract
Background/Objectives: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID—including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell—that have persisted [...] Read more.
Background/Objectives: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID—including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell—that have persisted for at least two years after acute infection, which we define as “persistent Long COVID”. Additionally, the study aimed to identify clinical features and blood biomarkers associated with persistent Long COVID symptoms. Methods: We sent a detailed long COVID symptoms questionnaire to an existing cohort of 1258 vaccinated adults (age 18–79 years) who had mild infection (e.g., non-hospitalized) SARS-CoV-2 Delta variant 2 years earlier. These individuals had comprehensive datasets, including blood samples, available for further analysis. We estimated prevalence of persistent long COVID two years post-infection using weighted adjustment (Horvitz–Thompson estimator) to overcome reporting bias. Multivariable logistic regression models were used to determine association of clinical features and blood biomarkers (pre-infection SARS-CoV-2 RBD-IgG, SARS-CoV-2 neutralizing antibodies, and pre-infection and post-infection neurofilament light) with prevalence of persistent long COVID. Results: N = 323 participants responded to the survey, of whom N = 74 (23%) reported at least one long COVID symptom that had persisted for two years after the acute infection. Weighted prevalence of persistent long COVID symptoms was 21.5% (95% CI = 16.7–26.3%). Female gender, smoking, and severity of acute COVID-19 infection were significantly associated with persistent Long COVID. The blood biomarkers assessed were not significantly associated with persistent Long COVID. Conclusions: Among vaccinated adults two years after mild infection with Delta variant SARS-CoV-2, persistent symptoms attributed to Long COVID are extremely common, certain subgroups are at higher risk, and further research into biological mechanisms and potential treatment targets is needed. Full article
(This article belongs to the Special Issue Beyond Acute: Navigating Long COVID and Post-Viral Complications)
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