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Viruses
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Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition
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Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Coronaviruses".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 7558

Special Issue Editor

Dr. Daniele Focosi

E-Mail Website
Guest Editor
North-Western Tuscany Blood Bank, Pisa University Hospital, 56124 Pisa, Italy
Interests: emerging viral infections; SARS-CoV-2; convalescent plasma; passive immunotherapies; vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issues, titled “Emerging Concepts in SARS-CoV-2 Biology and Pathology” and “Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0”.

Much has been learnt about SARS-CoV-2 biology, but much also remains to be learned. Although it currently mostly drives pathology in immunocompromised patients, SARS-CoV-2 is still evolving at rates much higher than those of other human RNA viruses, with convergence with moving Spike targets while globally increasing its genetic and serological distance. The source of the pandemic has been redefined as a panzootic disease of placental mammals, leaving room for reverse zoonoses. The virus has also been shown to be able to compartmentalize and persist, even in immunocompetent hosts, potentially causing long-lasting symptoms for which directly acting antivirals are under investigation as treatment. Unfortunately, many emergency-use authorized drugs provide marginal benefits in vaccinated patients, and none of the anti-Spike monoclonal antibodies authorized so far are effective against emerging Omicron variants. Fundamental virology has discovered how SARS-CoV-2 carries miRNA-like molecules that are able to suppress the immune response and how the genome can integrate. In this Special Issue, we will collect articles discussing advances in epidemiology and fundamental virology, as well as novel therapeutics.

Dr. Daniele Focosi
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 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

  • SARS-CoV-2
  • epidemiology
  • virology
  • therapeutics
  • zoonoses

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Published Papers (5 papers)

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15 pages, 356 KB  
Article
Association of Initial Chest CT Findings, CT Severity Score and Clinical Parameters with ICU Admission in Hospitalized COVID-19 Patients
by Aleksandra Milenkovic, Simon Nikolic, Jelena Aritonovic Pribakovic, Branislava Radovic, Aleksandra Ilic, Milica Stevanovic, Sara Kovacevic, Kristina Bulatovic, Jelena Milovanovic, Arijeta Kostic and Aleksandra Janicevic
Viruses 2026, 18(5), 528; https://doi.org/10.3390/v18050528 - 30 Apr 2026
Viewed by 634
Abstract
The aim of this study was to evaluate the association between baseline clinical and CT characteristics and to identify factors associated with intensive care unit (ICU) admission in hospitalized COVID-19 patients. This retrospective study included 176 adult patients with laboratory-confirmed SARS-CoV-2 infection hospitalized [...] Read more.
The aim of this study was to evaluate the association between baseline clinical and CT characteristics and to identify factors associated with intensive care unit (ICU) admission in hospitalized COVID-19 patients. This retrospective study included 176 adult patients with laboratory-confirmed SARS-CoV-2 infection hospitalized at the COVID Hospital of the Clinical Hospital Center Kosovska Mitrovica during 2021–2022 (Delta and Omicron variants). Patients were divided into two groups according to intensive care unit requirement: those treated in a general inpatient ward (No ICU) and those requiring ICU admission (ICU group). Demographic and clinical characteristics, lifestyle factors, CT findings, CT severity score (CTSS) values, and therapeutic interventions were compared between groups. Of the total cohort, 113 patients (64%) were hospitalized in a general inpatient ward, while 63 (36%) required intensive care unit admission. Independent predictors of ICU admission identified in the multivariate logistic regression analysis were obesity (B = 2.96, p < 0.001), dyspnea (B = 1.51, p = 0.041), higher CT severity score (B = 0.68, p < 0.001), and lower glucose levels (B = −0.27, p = 0.014). Furthermore, for each one-point increase in the CTSS, the odds of ICU admission nearly doubled (OR = 1.97). Total CT score values above the cut-off point (15.0) demonstrated significant reliability in discriminating the need for ICU transfer in patients with COVID-19. These findings suggest that combined clinical and radiological assessment at hospital admission may facilitate early identification of patients at high risk of requiring ICU care, with the CT severity score representing the strongest radiological predictor. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition)
19 pages, 11198 KB  
Article
Targeting SARS-CoV-2 Mpro and PLpro by Repurposing Clinically Approved Drugs
by Qiaoyu Fang, Meng Lu, Derong Chen, Liangxu Xie, Wenxu Hong, Zhang Zhang and Xuqiao Hu
Viruses 2025, 17(12), 1564; https://doi.org/10.3390/v17121564 - 29 Nov 2025
Viewed by 919
Abstract
SARS-CoV-2 virus contains two highly conserved domains, the papain-like protease (PLpro) and main protease (Mpro), which play important roles in virus replication, immune suppression, and the induction of inflammation in host tissue. In this study, we applied small-molecule chip screening, enzymatic assays, SARS-CoV-2 [...] Read more.
SARS-CoV-2 virus contains two highly conserved domains, the papain-like protease (PLpro) and main protease (Mpro), which play important roles in virus replication, immune suppression, and the induction of inflammation in host tissue. In this study, we applied small-molecule chip screening, enzymatic assays, SARS-CoV-2 spike pseudotyped virus detection and molecular docking to find potential Mpro or PLpro inhibitors. Two small molecules, oxytocin and risedronate sodium, stood out in drug repurposing. Oxytocin and risedronate sodium were shown to influence the activities of Mpro and PLpro, thereby preventing the virus from replication, which may alleviate SARS-CoV-2 infection. Thus, oxytocin, risedronate sodium, and cephalosporins may expand the drug library for treating coronavirus infection. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition)
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24 pages, 3590 KB  
Article
Mesocricetus auratus (Golden Syrian Hamster) Experimental Model of SARS-CoV-2 Infection Reveals That Lung Injury Is Associated with Phenotypic Differences Between SARS-CoV-2 Variants
by Daniela del Rosario Flores Rodrigues, Alexandre dos Santos da Silva, Arthur Daniel Rocha Alves, Bárbara Araujo Rossi, Richard de Almeida Lima, Sarah Beatriz Salvador Castro Faria, Oswaldo Gonçalves Cruz, Rodrigo Muller, Julio Scharfstein, Amanda Roberta Revoredo Vicentino, Aline da Rocha Matos, João Paulo Rodrigues dos Santos, Pedro Paulo Abreu Manso, Milla Bezerra Paiva, Debora Ferreira Barreto-Vieira, Gabriela Cardoso Caldas, Marcelo Pelajo Machado and Marcelo Alves Pinto
Viruses 2025, 17(8), 1048; https://doi.org/10.3390/v17081048 - 28 Jul 2025
Cited by 1 | Viewed by 2633
Abstract
Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute [...] Read more.
Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition)
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17 pages, 1274 KB  
Article
The Role of Comorbidities in COVID-19 Severity
by Sandra König, Ugne Vaskyte, Maria Boesing, Giorgia Lüthi-Corridori and Joerg Daniel Leuppi
Viruses 2025, 17(7), 957; https://doi.org/10.3390/v17070957 - 7 Jul 2025
Cited by 4 | Viewed by 1592
Abstract
Background: COVID-19 has led to significant global morbidity and mortality, with clinical outcomes varying widely among individuals. Understanding the impact of comorbidities on COVID-19 outcomes is essential for improving patient management. To date, analyses of comorbidities affecting COVID-19 severity in a heterogeneous Swiss [...] Read more.
Background: COVID-19 has led to significant global morbidity and mortality, with clinical outcomes varying widely among individuals. Understanding the impact of comorbidities on COVID-19 outcomes is essential for improving patient management. To date, analyses of comorbidities affecting COVID-19 severity in a heterogeneous Swiss cohort across multiple outbreak waves are unavailable. The objective of this study was to explore the role of comorbidities on COVID-19 severity in hospitalized patients from a diverse Swiss cohort and to evaluate the association between comorbidities and specific in-hospital complications. Methods: This retrospective, observational, single-center study included adult patients who were hospitalized for COVID-19 for at least one night at the Cantonal Hospital Baselland, Switzerland (KSBL), between March 2020 and December 2021. Logistic regression analyses adjusted for age and gender were performed to analyze the association between comorbidities and critical condition (defined as severe disease or in-hospital death) and complications. Results: A total of 1124 patients were included in the study (median age 66, range 19–100 years, 60% male). A total of 76% of patients had at least one comorbidity. The most common comorbidities were arterial hypertension (47%), obesity (27%), and diabetes mellitus (24%). Overall, 16% of patients experienced a critical condition, and 25.5% had any type of complication. Patients without comorbidities had the lowest rates of critical condition (5.3%) and complications (10.2%). Obesity (OR 2.01, p < 0.001), diabetes mellitus (OR 1.67, p = 0.004), arterial hypertension (OR 1.65, p = 0.006), arrhythmia (OR1.87, p = 0.003), and chronic obstructive pulmonary disease (OR 2.72, p < 0.001) were found to be associated with critical condition. The most frequently observed complication was acute kidney failure, affecting 17.1% of the study population, while patients with arrhythmia showed the highest overall complication rate (42%). Conclusions: Our findings are consistent with previous research, confirming the relevance of specific comorbidities as key risk factors for critical COVID-19 outcomes. Among all comorbid conditions evaluated, asthma appeared to have the least impact on disease severity. Future research should focus on the impact of the combination of comorbidities on the disease severity of COVID-19, as well as the long-term effects of COVID-19 for patients with certain comorbidities. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition)
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12 pages, 2491 KB  
Case Report
Pericarditis in a Child with COVID-19 Complicated by Streptococcus pneumoniae Sepsis: A Case Report
by Mădălina Maria Merișescu, Mihaela Oroș, Gheorghiță Jugulete, Bianca Borcoș, Larisa Mirela Răduț, Alexandra Totoianu and Anca Oana Dragomirescu
Viruses 2025, 17(12), 1567; https://doi.org/10.3390/v17121567 - 30 Nov 2025
Viewed by 917
Abstract
Background: Pediatric SARS-CoV-2 infection is usually mild, but in rare cases may lead to severe complications. Early recognition and comprehensive management are critical for favorable outcomes. Case Presentation: We present the case of a 2-year-old girl, previously healthy and unvaccinated against Streptococcus Pneumoniae [...] Read more.
Background: Pediatric SARS-CoV-2 infection is usually mild, but in rare cases may lead to severe complications. Early recognition and comprehensive management are critical for favorable outcomes. Case Presentation: We present the case of a 2-year-old girl, previously healthy and unvaccinated against Streptococcus Pneumoniae (S. pneumoniae), who developed SARS-CoV-2 infection and acute otitis media. Initial laboratory evaluation revealed leukocytosis with neutrophilia and increased inflammatory markers. Antiviral and antibiotic treatment was initiated, but she remained febrile, polypneic, and tachycardic. The diagnosis of MIS-C was excluded; there was no involvement of two organs, and infection with S. pneumoniae serotype 19 F was identified. Given the unfavorable evolution, corticosteroid therapy and immunoglobulin were instituted, and subsequently, following the antibiogram result, antibiotic therapy was escalated to Meropenem and Linezolid. Clinical and laboratory parameters improved, but pericarditis with a small fluid slide and ECG changes were associated. The evolution was favorable with complete cardiac recovery at 30 days. Conclusion: This case highlights the importance of vigilant assessment for secondary bacterial infections and cardiac complications in pediatric COVID-19. Prompt recognition and targeted treatment are essential, and pneumococcal vaccination remains a fundamental preventive measure. Moreover, the scarcity of literature documenting SARS-CoV-2 infections complicated by pericarditis further underscores the uniqueness of this case and its relevance for specialists in the field. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition)
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