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Evolutionary Challenges of RNA Viruses: Insights from SARS-CoV-2 Variants and...
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Evolutionary Challenges of RNA Viruses: Insights from SARS-CoV-2 Variants and Emerging Respiratory Diseases

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

Deadline for manuscript submissions: 30 November 2025 | Viewed by 2836

Special Issue Editor

Dr. Ahmed El-Shamy

E-Mail Website
Guest Editor
Master of Pharmaceutical Science Program, College of Graduate Studies, California Northstate University, Elk Grove, CA, USA
Interests: viral hepatitis; DAA; liver cancer; novel therapies; lipid metabolism; emerging infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Rapid evolutionary changes in RNA viruses are central to the emergence, spread, and control of respiratory diseases. This evolutionary adaptability poses a continuous challenge to public health efforts as it requires constant surveillance, updates to vaccines, and readiness to manage new outbreaks or variants that may arise. In addition, evolutionary changes in RNA viruses can cause the re-emergence of previously controlled viral outbreaks, particularly when mutations result in more virulent or transmissible forms. For instance, the evolution of avian influenza strains, like H5N1 and H7N9, has led to periodic outbreaks, raising concerns about their potential to cause future pandemics. Moreover, prolonged infections in immunocompromised COVID-19 patients have been linked to the emergence of certain mutations seen in SARS-CoV2 variants of concern. Thus, understanding and monitoring the evolutionary dynamics of RNA viruses are crucial to mitigating future viral-induced respiratory pandemics.

Dr. Ahmed El-Shamy
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. 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

  • RNA viruses
  • evolution
  • influenza
  • SARS-CoV2
  • COVID-19
  • respiratory diseases

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Related Special Issue

Published Papers (3 papers)

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Research

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20 pages, 1284 KB  
Article
Intra-Host Evolution of SARS-CoV-2 During Persistent Infection of Pediatric COVID-19 Patients
by Charlie R. Boyle, Tien Doan, Estefany Rios-Guzman, Jessica Maciuch, Lacy M. Simons, Dulce S. Garcia, David B. Williams, Arghavan Alisoltani, Egon A. Ozer, Ramon Lorenzo-Redondo and Judd F. Hultquist
Viruses 2025, 17(10), 1313; https://doi.org/10.3390/v17101313 - 28 Sep 2025
Abstract
The Coronavirus disease 2019 (COVID-19) pandemic had a profound global impact, yet children exhibited distinct clinical and epidemiological patterns compared to adults. Pediatric cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were generally characterized by milder disease, lower hospitalization rates, and few [...] Read more.
The Coronavirus disease 2019 (COVID-19) pandemic had a profound global impact, yet children exhibited distinct clinical and epidemiological patterns compared to adults. Pediatric cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were generally characterized by milder disease, lower hospitalization rates, and few long-term sequelae. However, a subset of children developed severe complications such as multisystem inflammatory syndrome in children (MIS-C), highlighting the heterogeneity in disease presentation. Differences in immune system maturity and comorbidities likely contribute to the age-dependent manifestation of SARS-CoV-2 and other respiratory viruses. Persistent SARS-CoV-2 infection, particularly in immunocompromised individuals, has been implicated in the emergence of new viral variants with immune escape characteristics due to ongoing viral replication in the presence of selective pressure. While SARS-CoV-2 evolution in persistently infected adults has been well-documented, it is less clear how the virus evolves during persistent infection in the pediatric population. To address this question, we performed viral whole genome sequencing of longitudinal specimens collected from immunocompetent and immunocompromised pediatric COVID-19 patients. Similarly to what has been observed in adult cohorts, mutations associated with enhanced viral fitness and immune escape arose intra-host over time. Intra-host diversity accumulated at similar rates in immunocompetent and immunocompromised children, though more mutations overall were observed in the immunocompromised cohort due to the longer infection time courses. Overall, we identified similar viral evolutionary trends over the course of infection despite clinical differences in pediatric COVID-19 manifestation and severity. This similarity suggests that persistent infection in children may be an additional, but not unique, source of ongoing viral diversification. Full article
(This article belongs to the Special Issue Evolutionary Challenges of RNA Viruses: Insights from SARS-CoV-2 Variants and Emerging Respiratory Diseases)
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Review

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17 pages, 639 KB  
Review
Gastrointestinal Infiltration in Influenza Virus Infection: Mechanisms and Clinical Insights
by Aakriti Dua, Bhavna Trehan, Shymaa E. Bilasy, Catherine Yang and Ahmed ElShamy
Viruses 2025, 17(9), 1187; https://doi.org/10.3390/v17091187 - 29 Aug 2025
Viewed by 889
Abstract
Background: Influenza, a primarily respiratory illness, frequently manifests with gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, and abdominal pain. In this review, we analyze mechanisms describing GI infiltration and subsequent involvement of the GI system during influenza infection. Direct mechanisms involve the [...] Read more.
Background: Influenza, a primarily respiratory illness, frequently manifests with gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, and abdominal pain. In this review, we analyze mechanisms describing GI infiltration and subsequent involvement of the GI system during influenza infection. Direct mechanisms involve the presence of viral particles in the GI tract and binding to sialic acid receptor, α2,3 and α2,6 linkages. The influenza virus may gain access to gut tissue via swallowing of respiratory secretions, hematogenous spread, or lymphocytic migration via the lung–gut axis. Indirect mechanisms involve immune system dysregulation via cytokine, interferon, and leukotriene flux, upregulation of consequential apoptotic pathways, or gut microbiome dysbiosis. Together, they promote secondary GI opportunistic infections. These findings improve our knowledge of GI infiltration during influenza infection which may aid in effective clinical diagnosis and treatment, ultimately improving patient outcomes. Full article
(This article belongs to the Special Issue Evolutionary Challenges of RNA Viruses: Insights from SARS-CoV-2 Variants and Emerging Respiratory Diseases)
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16 pages, 604 KB  
Review
An Update on RNA Virus Discovery: Current Challenges and Future Perspectives
by Humberto Debat and Nicolas Bejerman
Viruses 2025, 17(7), 983; https://doi.org/10.3390/v17070983 - 15 Jul 2025
Viewed by 1004
Abstract
The relentless emergence of RNA viruses poses a perpetual threat to global public health, necessitating continuous efforts in surveillance, discovery, and understanding of these pathogens. This review provides a comprehensive update on recent advancements in RNA virus discovery, highlighting breakthroughs in technology and [...] Read more.
The relentless emergence of RNA viruses poses a perpetual threat to global public health, necessitating continuous efforts in surveillance, discovery, and understanding of these pathogens. This review provides a comprehensive update on recent advancements in RNA virus discovery, highlighting breakthroughs in technology and methodologies that have significantly enhanced our ability to identify novel viruses across diverse host organisms. We explore the expanding landscape of viral diversity, emphasizing the discovery of previously unknown viral families and the role of zoonotic transmissions in shaping the viral ecosystem. Additionally, we discuss the potential implications of RNA virus discovery on disease emergence and pandemic preparedness. Despite remarkable progress, current challenges in sample collection, data interpretation, and the characterization of newly identified viruses persist. Our ability to anticipate and respond to emerging respiratory threats relies on virus discovery as a cornerstone for understanding RNA virus evolution. We address these challenges and propose future directions for research, emphasizing the integration of multi-omic approaches, advanced computational tools, and international collaboration to overcome barriers in the field. This comprehensive overview aims to guide researchers, policymakers, and public health professionals in navigating the intricate landscape of RNA virus discovery, fostering a proactive and collaborative approach to anticipate and mitigate emerging viral threats. Full article
(This article belongs to the Special Issue Evolutionary Challenges of RNA Viruses: Insights from SARS-CoV-2 Variants and Emerging Respiratory Diseases)
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