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Viruses
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Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics
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Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: 15 May 2025 | Viewed by 8407

Special Issue Editors

Dr. Karolina Akinosoglou

E-Mail Website
Guest Editor
Department of Medicine, University General Hospital of Patras, 26504 Rio, Greece
Interests: sepsis; COVID-19; HIV; infections in obstetrics and gynecology; antimicrobial resistance; hospital-acquired infections
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Charalambos Gogos

E-Mail Website
Guest Editor
Department of Medicine, University of Patras, Metropolitan General Athens, Rio, Greece
Interests: sepsis; COVID-19; immunology of infection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, titled "Viral Sepsis: Pathogenesis and Therapeutics", delves into the complex and critical realm of sepsis, a life-threatening condition triggered by a viral infection. We hope that this compilation of articles will bring together cutting-edge research and insights from experts in the field to shed light on the multifaceted aspects of viral sepsis. The Special Issue begins by exploring the pathogenesis of viral sepsis, elucidating the intricate interplay between the virus and the host immune response. It delves into the molecular mechanisms that underlie the dysregulation of the immune system, the cytokine storms, and organ dysfunction that characterize this devastating condition. Furthermore, it will examine the latest diagnostic tools and biomarkers that can aid in the early detection and monitoring of viral sepsis, facilitating timely intervention. One of the central themes of this Special Issue will also be the development of therapeutics for viral sepsis. It presents a comprehensive overview of the current state of antiviral treatments, immunomodulatory strategies, supportive therapies and potential vaccines aimed at mitigating the severity of viral sepsis and improving patient outcomes. Researchers and clinicians alike will find valuable insights into the challenges and opportunities in the quest to develop effective therapies. Additionally, the Special Issue will explore the role of precision medicine in tailoring treatment approaches to individual patients, taking into account their genetic and immunological profiles.

Dr. Karolina Akinosoglou
Prof. Dr. Charalambos Gogos
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 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. 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

  • viral sepsis
  • HIV
  • HBV
  • HCV
  • EBV
  • HDV
  • HEV
  • CMV
  • HSV
  • HPV
  • influenza
  • RSV
  • COVID-19
  • SARS-CoV-2
  • other viruses
  • viral infection
  • sepsis
  • pathogenesis
  • diagnosis
  • therapy
  • biomarkers
  • vaccination

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Published Papers (6 papers)

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Research

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13 pages, 236 KiB  
Article
Predictors of Unfavorable Outcomes in COVID-19-Related Sepsis: A Prospective Cohort Study
by Diana-Maria Mateescu, Ioana Cotet, Cristina Guse, Catalin Prodan-Barbulescu, Norberth-Istvan Varga, Stela Iurciuc, Maria-Laura Craciun, Adrian-Cosmin Ilie and Alexandra Enache
Viruses 2025, 17(4), 455; https://doi.org/10.3390/v17040455 - 21 Mar 2025
Viewed by 158
Abstract
Sepsis is a leading cause of mortality in critically ill patients, arising from a dysregulated immune response to infection. While traditionally associated with bacterial pathogens, severe COVID-19 can induce a sepsis-like syndrome, characterized by systemic inflammation, endothelial dysfunction, and coagulation abnormalities. This study [...] Read more.
Sepsis is a leading cause of mortality in critically ill patients, arising from a dysregulated immune response to infection. While traditionally associated with bacterial pathogens, severe COVID-19 can induce a sepsis-like syndrome, characterized by systemic inflammation, endothelial dysfunction, and coagulation abnormalities. This study aimed to assess the prognostic value of age, inflammatory markers, coagulation dysfunction, comorbidity burden, and lung involvement on computer tomography (CT) scans in predicting poor outcomes. We conducted a prospective cohort study including 163 patients diagnosed with COVID-19-related sepsis. Univariate and multivariable logistic regression analyses were performed to identify the independent predictors of unfavorable outcomes. Higher D-dimer (OR: 1.417, p = 0.020) and C-reactive protein (CRP) levels (OR: 1.010, p = 0.027) were independently associated with poor outcomes. A greater than 50% lung involvement on CT (OR: 1.774, p = 0.025) was also a significant predictor. The Charleson Comorbidity Index (CCI) showed a strong trend toward significance (p = 0.065), while age lost statistical significance after adjusting for comorbidities. Our findings suggest that D-dimers, CRP, and lung involvement on CT are key independent predictors of poor outcomes in COVID-19-related sepsis. These results emphasize the importance of inflammatory and coagulation markers, alongside comorbidity burden, in early risk assessment. Further prospective studies are warranted to refine predictive models for severe COVID-19 cases complicated by sepsis. Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)
16 pages, 1638 KiB  
Article
Elevated Serum Presepsin Identifies Herpes Simplex Virus-1 Reactivation in COVID-19 Patients
by Patricia Mester, Dennis Keller, Claudia Kunst, Stephan Schmid, Sabrina Krautbauer, Martina Müller, Christa Buechler and Vlad Pavel
Viruses 2025, 17(3), 357; https://doi.org/10.3390/v17030357 - 28 Feb 2025
Viewed by 249
Abstract
Presepsin, a cleaved peptide of soluble CD14, may become a promising biomarker for assessing disease severity and mortality in coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 frequently develop bacterial and fungal superinfections, as well as herpes simplex virus-1 (HSV-1) reactivation, which may [...] Read more.
Presepsin, a cleaved peptide of soluble CD14, may become a promising biomarker for assessing disease severity and mortality in coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 frequently develop bacterial and fungal superinfections, as well as herpes simplex virus-1 (HSV-1) reactivation, which may exacerbate disease progression. This study aimed to evaluate the impact of concomitant infections on serum presepsin levels. Serum presepsin levels were measured using an enzyme-linked immunosorbent assay (ELISA) in 63 patients with moderate COVID-19, 60 patients with severe disease, and 49 healthy controls. Correlations with procalcitonin and the presence of superinfections or HSV-1 reactivation were assessed. Consistent with previous studies, serum presepsin levels were the highest in patients with severe COVID-19 (p = 0.002 compared to patients with moderate disease). Within this group, non-survivors exhibited significantly elevated presepsin levels (p = 0.027). A positive correlation between presepsin and procalcitonin was observed in both moderate and severe COVID-19 cases. Patients with bacterial or fungal superinfections showed presepsin levels comparable to those without secondary infections. However, presepsin levels were markedly elevated in patients with HSV-1 reactivation (p = 0.002). After excluding patients with HSV-1 reactivation, presepsin levels no longer differed between moderate and severe COVID-19 cases, though they remained higher than in healthy controls (p < 0.001 for both comparisons). In conclusion, these findings suggest that elevated serum presepsin levels in severe COVID-19 are primarily driven by HSV-1 reactivation rather than bacterial or fungal superinfections. Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)
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14 pages, 715 KiB  
Article
Pregnancy and COVID-19: Comparing ICU Outcomes for Pregnant and Nonpregnant Women
by Małgorzata Lipińska-Gediga, Waldemar Goździk, Jakub Śmiechowicz and Barbara Adamik
Viruses 2025, 17(1), 51; https://doi.org/10.3390/v17010051 - 31 Dec 2024
Viewed by 817
Abstract
Background: This study compares organ dysfunction, treatment strategies, and unfavorable outcome rates between pregnant and nonpregnant women admitted to the ICU with severe COVID-19, highlighting the increased susceptibility of pregnant women to respiratory infections due to physiological changes. Methods: A retrospective, age-matched study [...] Read more.
Background: This study compares organ dysfunction, treatment strategies, and unfavorable outcome rates between pregnant and nonpregnant women admitted to the ICU with severe COVID-19, highlighting the increased susceptibility of pregnant women to respiratory infections due to physiological changes. Methods: A retrospective, age-matched study was conducted at a referral center specializing in critical care for pregnant women. Data from 14 pregnant/postpartum and 11 nonpregnant women were analyzed at ICU admission and on days 3, 5, and 7. Results: Acute respiratory distress syndrome was diagnosed in 100% of the pregnant/postpartum group and 64% of the nonpregnant group (p = 0.026). Inflammatory parameters were similar between groups, except for lower ferritin levels in the pregnant/postpartum group compared to the nonpregnant (120 vs. 568 µg/L at admission and 90 vs. 616 µg/L on day 3). Creatinine, lactate, and lactate dehydrogenase levels were significantly lower in the pregnant/postpartum group. A reduction in the SOFA score was observed over time in the pregnant/postpartum group (from 7.0 to 4.0 points, p = 0.009), while no change was noticed in the nonpregnant group (from 3.0 to 2.5 points, p = 0.181). Unfavorable outcome rates were similar, with two patients from each group succumbing to the disease (p = 0.604). Conclusions: The findings suggest that pregnancy does not increase the risk of unfavorable outcomes among women with severe COVID-19 receiving ICU treatment. However, additional studies with larger sample sizes are needed to validate these observations. Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)
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16 pages, 279 KiB  
Article
Understanding the Impact of COVID-19 on Roma Vulnerable Communities in Western Romania: Insights and Predictive Factors from a Retrospective Study
by Ionut Dragos Capraru, Catalin Marian, Dan Dumitru Vulcanescu, Sonia Tanasescu, Tiberiu Liviu Dragomir, Teodora Daniela Marti, Casiana Boru, Cecilia Roberta Avram, Monica Susan and Cristian Sebastian Vlad
Viruses 2024, 16(3), 435; https://doi.org/10.3390/v16030435 - 12 Mar 2024
Cited by 1 | Viewed by 1756
Abstract
Background: The COVID-19 pandemic disproportionately affected vulnerable populations like Roma patients in Western Romania due to marginalization and limited healthcare access. Methods: A retrospective study analyzed COVID-19 cases between March 2020 and August 2022 using data from the Directorate of Public Health in [...] Read more.
Background: The COVID-19 pandemic disproportionately affected vulnerable populations like Roma patients in Western Romania due to marginalization and limited healthcare access. Methods: A retrospective study analyzed COVID-19 cases between March 2020 and August 2022 using data from the Directorate of Public Health in Timis county. Demographic, epidemiological, clinical, and laboratory data were assessed, along with risk factors and biomarkers for ICU admission and mortality prediction. The following biomarkers were assessed: C-reactive protein (CRP), ferritin (FER), IL-6, D-dimers, lactate dehydrogenase (LDH), high density lipoprotein cholesterol (HDL), and 25-OH vitamin D (25-OHD). Results: In comparison with the general population (GP), Roma patients were more overweight (p = 0.0292), came from rural areas (p = 0.0001), could not recall transmission source (p = 0.0215), were admitted to the intensive care unit (ICU, p = 0.0399) more frequently, had worse symptomatology (p = 0.0490), showed more elevated levels of CRP (p = 0.0245) and IL-6 (p < 0.0001) and lower levels of HDL (p = 0.0008) and 25-OHD (p = 0.0299). A stronger, significant correlation was observed between CRP and severity (rho = 0.791 vs. 0.433 in GP), and an inverse stronger significant one was observed between HDL and severity (rho = −0.850 vs. −0.734 in GP) in the Roma patients. The male sex continues to be an important risk factor for ICU admission (OR = 2.379) and death (OR = 1.975), while heavy smoking was more important in relation to ICU admission (OR = 1.768). Although the Roma ethnicity was 1.454 times more at risk of ICU admission than the GP, this did not prove statistically significant (p = 0.0751). CRP was the most important predictive factor in regards to admission to the ICU for both Roma (OR = 1.381) and the GP (OR = 1.110) and in regards to death (OR = 1.154 for Roma, OR = 1.104 for GP). A protective effect of normal values of HDL and 25-OHD was observed in the GP for both ICU admission (OR = 0.947, 0.853, respectively) and death (OR = 0.920, 0.921, respectively), while for the Roma group, normal 25-OHD values were only considered protective in regards to death (OR = 0.703). Cutoff values for ICU admission were 28.98 mg/L for Roma and 29.03 mg/L for GP patients, with high specificity for both groups (over 95). Conclusions: Higher rates of ICU admissions, severe symptomatology, and distinct laboratory biomarker profiles among Roma patients emphasize the critical importance of personalized care strategies and targeted interventions to mitigate the disproportionate burden of COVID-19 on vulnerable communities. CRP values at admission have had a clear impact as a risk assessment biomarker for Roma patients, while the significance of IL-6, HDL, and 25-OHD should also not be overlooked in these patients. Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)

Review

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18 pages, 443 KiB  
Review
Macrophage Activation Syndrome in Viral Sepsis
by Despoina Papageorgiou, Charalambos Gogos and Karolina Akinosoglou
Viruses 2024, 16(7), 1004; https://doi.org/10.3390/v16071004 - 22 Jun 2024
Cited by 2 | Viewed by 2517
Abstract
Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor [...] Read more.
Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor clinical outcomes. During the COVID-19 pandemic, patients with severe manifestations developed features similar to those of MAS, although these characteristics remained well defined within the lung. Additionally, other viral infections including EBV, the herpes family of viruses, hepatitis viruses, influenza, HIV, and hemorrhagic fevers can be complicated by MAS. The diagnosis and management of the condition remain challenging due to the lack of consensus on specific guidelines, especially among the adult population. Currently, therapeutic options primarily rely on medications that are typically used to treat primary hemophagocytic lymphohistiocytosis, such as corticosteroids and etoposide. In addition, cytokine-targeted therapies present promising treatment options. The objective of this review is to discuss the emergence of MAS in the context of viral infections including, but not limited to, its occurrence in COVID-19. Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)
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15 pages, 654 KiB  
Review
Impact of Prior COVID-19 Immunization and/or Prior Infection on Immune Responses and Clinical Outcomes
by Achilleas Livieratos, Charalambos Gogos and Karolina Akinosoglou
Viruses 2024, 16(5), 685; https://doi.org/10.3390/v16050685 - 26 Apr 2024
Cited by 7 | Viewed by 2072
Abstract
Cellular and humoral immunity exhibit dynamic adaptation to the mutating SARS-CoV-2 virus. It is noteworthy that immune responses differ significantly, influenced by whether a patient has received vaccination or whether there is co-occurrence of naturally acquired and vaccine-induced immunity, known as hybrid immunity. [...] Read more.
Cellular and humoral immunity exhibit dynamic adaptation to the mutating SARS-CoV-2 virus. It is noteworthy that immune responses differ significantly, influenced by whether a patient has received vaccination or whether there is co-occurrence of naturally acquired and vaccine-induced immunity, known as hybrid immunity. The different immune reactions, conditional on vaccination status and the viral variant involved, bear implications for inflammatory responses, patient outcomes, pathogen transmission rates, and lingering post-COVID conditions. Considering these developments, we have performed a review of recently published literature, aiming to disentangle the intricate relationships among immunological profiles, transmission, the long-term health effects post-COVID infection poses, and the resultant clinical manifestations. This investigation is directed toward understanding the variability in the longevity and potency of cellular and humoral immune responses elicited by immunization and hybrid infection. Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)
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